Environment and the Brain 3 Flashcards
True or false? Explain your answer if appropriate. (1)
Diet sits on a spectrum of impact on brain health, with a Mediterranean and anti-inflammatory diet on the good end, and Ultra-processed and Western diet on the bad end.
True
Give an example of a diet which is used as a medical treatment. (1)
Ketogenic diet for epilepsy
Give three circumstances where the ketogenic diet is used as a treatment for epilepsy. (3)
- In drug-resistant epilepsy
- In children especially (but can also be used in adults)
- In GLUT1 deficiency (where it is the standard treatment)
Does the ketogenic diet lead to improved symptoms in all patients with epilepsy? (1)
No
Complete the sentence regarding a ketogenic diet and epilepsy. (4)
When using a ketogenic diet to help treat epilepsy, patients must be monitored by a medical team to ensure …………………… of the diet, and …………………….
However, this treatment has been used for ……………….. years, and is advised by ……………………….
Effectiveness
nutritional balance
more than 100
the NICE guidelines
Describe the ketogenic diet, in terms of the intake of the following food groups. (3)
a) fat
b) carbohydrate
c) protein
a) high fat (75% of diet)
b) low carbohydrate (5% of diet)
c) controlled protein intake (about 20% of diet)
Describe how the ketogenic diet alters the body and brain’s main energy source. (1)
Changes the main energy source from carbohydrates (glucose) to fats (ketones)
Give five ways in which the ketogenic diet impacts neurobiology. (5)
- Increases mitochondrial function and biogenesis
- Reduces oxidative stress
- Impacts gut-brain axis via changes in gut microbiota
- Mediates reduction in neuroinflammation
- Widespread changes in gene expression
Suggest a mechanism by which the ketogenic diet may have an impact on neurobiology, such as gene changes, neuroinflammation, and mitochondrial function. (1)
Changes likely mediated by circulating miRNA and epigenetic molecules
The ketogenic diet is able to result in widespread changes in gene expression in the brain.
Give three general categories of genes (what brain function they are associated with) which are downregulated by a ketogenic diet. (3)
- Ion channels
- Neurotransmission
- Synapse structure
Suggest a general group of ion channel genes which may be downregulated in a ketogenic diet. (1)
Potassium channels
The ketogenic diet is able to result in widespread changes in gene expression in the brain.
Give three general categories of genes (what brain function they are associated with) which are upregulated by a ketogenic diet. (3)
- Ion channels
- Synapse structure
- Growth factor
Suggest a general group of ion channel genes which may be upregulated in a ketogenic diet. (1)
Calcium channels
Is the MAOA gene upregulated or downregulated in a ketogenic diet? (1)
Downregulated
Is the BDNF gene upregulated or downregulated in a ketogenic diet? (1)
Upregulated
Is gene expression of orexins upregulated or downregulated in a ketogenic diet? (1)
What role do the orexins play? (1)
- Downregulated
- Play a role in wakefulness
Fill the gaps relating to GLUT1 deficiency. (3)
GLUT1 deficiency results in low ………………. levels in the CSF, and a developmental delay featuring ………………….. and ……………………
glucose
movement disorders
a generalised intractable epilepsy
ketogenic diet is the standard treatment for GLUT1 deficiency.
What is GLUT1? (1)
What is the role of GLUT1? (1)
Glucose transporter
Expressed on erythrocytes and BBB endothelial cells, so facilitates glucose transport across the BBB
Describe how a ketogenic diet is able to successfully treat GLUT1 deficiency. (3)
It provides an alternative energy source to the brain
Ketones cross the BBB via the MCT1 transporter
So it ‘doesn’t matter’ that GLUT1 isn’t working
Describe the metabolic pathway which allows fat to be used as energy in the brain. (5)
Lipolysis of dietary or stored fat
forms free fatty acids
FFAs can be converted to beta-hydroxybutyrate in liver mitochondria and then cross BBB
Or can cross BBB first and then be converted to beta-hydroxybutyrate
Beta-hydroxybutyrate converted to Acetyl-CoA in neurones and used in TCA cycle
Give two general food groups that the Mediterranean diet is based around. (2)
- Plant-based foods
- Healthy fats
Give six key stapes of the Mediterranean diet. (6)
- Seafood
- Fruits and vegetables
- Wholegrains
- Nuts and legumes
- Good oils/fats (olive oils, avocado, nuts)
- Water as a drink (plus a little bit of wine)
Complete the sentence relating to diet and mental health. (1)
A Mediterranean diet, or even just a healthy diet, are associated with less …………………….. symptoms.
depressive
When looking at studies investigating the impact of Mediterranean and Healthy diet on development of depression, in which of the following ranges would you expect the odds ratios to be in, for development of depression with Healthy/Mediterranean diet? (1)
a) 0-1
b) 1-2
c) 2-3
d) 3-4
Describe what this means in words. (1)
0-1
Mediterranean or healthy diet decreases risk of developing depression
Give four anti-inflammatory molecules found in a healthy/Mediterranean diet which may be responsible for the decrease in depressive symptoms seen with these diets. (4)
- Omega3 polyunsaturated fatty acids
- Unsaturated fatty acids
- Polyphenols
- Dietary fibre
Omega3 polyunsaturated fatty acids have been suggested to be part of a Mediterranean/healthy diet that decreases inflammation and is good for health.
Give a food group which contains high levels of omega3 fatty acids. (1)
Seafood
Unsaturated fatty acids have been suggested to be part of a Mediterranean/healthy diet that decreases inflammation and is good for health.
Give a food group which contains high levels of unsaturated fatty acids. (1)
Olive oil
Polyphenols have been suggested to be part of a Mediterranean/healthy diet that decreases inflammation and is good for health.
Give three foods which contain high levels of polyphenols. (3)
- Cocoa
- Blueberries
- Curcumin/turmeric
Dietary fibre has been suggested to be part of a Mediterranean/healthy diet that decreases inflammation and is good for health.
Give two food groups which contain high levels of dietary fibre. (2)
- Vegetables
- Wholemeal products
Suggest a way that dietary fibre may act as an anti-inflammatory food and confer a health benefit. (1)
Can promote beneficial gut microorganisms
Give the two most abundant components/molecules of the brain. (2)
FIRST = water
SECOND = fat
Give two general roles of fat in the brain. (2)
- Formation of cell membranes
- Formation of myelin
Apart from forming cell membranes and myelin, give two other specific roles for omega 3 and omega 6 fatty acids in the body and brain. (2)
- Precursors for molecules regulating blood pressure
- Precursors for molecules regulating inflammation
Approximately 90% of dietary fats are in what form? (1)
a) monoglycerides
b) diglycerides
c) triglycerides
c) triglycerides
Describe the general structure of a triglyceride molecule. (2)
3 fatty acid molecules
Attached to a glycerol backbone
Describe what is meant when referring to the alpha and omega end of a fatty acid. (2)
Alpha end is acid end with COOH
Omega end is other end with just carbon bonds and no functional group
Briefly describe the general structure of an omega-3 fatty acid. (2)
Polyunsaturated fatty acid
with a double bond connecting the 3rd and 4th carbon from the omega end
Name the three main omega-3 fatty acids. (3)
- Alphalinoleic acid (ALA)
- Eicosapentaenoic acid (EPA)
- Docosahexaenoic acid (DHA)
Name an omega-6 fatty acid which must be obtained from the diet. (1)
Linoleic acid
Fill the gaps relating to omega-3 fatty acids. (4)
The body is ………………………(able/unable) to make alphalinoleic acid. Therefore it ………………………(must/must not) be obtained from the diet.
ALA can then be used to make small amounts of two other omega-3 fatty acids, called ……………………… and ………………………..
unable
must
eicosapentaenoic acid (EPA)
docosahexaenoic acid (DHA)
Docosahexaenoic acid (DHA), an omega-3 fatty acid, can be synthesised from alphalinoleic acid (ALA), another omega-3 fatty acid, in the body.
Despite this, a dietary source of DHA is still required. Describe why this is. (3)
- ALA must also be obtained from the diet
- And only a small amount can then be converted to DHA
- So relying on ALA to DHA conversion is not a reliable way of getting DHAs
Docosahexaenoic acid is a dietary component which is thought to confer a health benefit.
What type of molecule is docosahexaenoic acid? (1)
Omega-3 fatty acid
Docosahexaenoic acid is an omega-3 fatty acid. Small amounts can be made in the body, however most must come from the diet.
Most people do not get enough omega-3 in their diet - is it more beneficial to add in more omega-3-rich foods, or to take supplements? (1)
Adding in more omega-3-rich foods
Docosahexaenoic acid (DHA) is an omega-3 fatty acid which is thought to be beneficial to the body and brain.
Higher DHA blood levels are associated with a lower risk of developing which two neurological illnesses? (2)
- All-cause dementia
- Alzheimer’s disease
In older adults (>65yrs), eating one or more fatty fish meals per week reduces the risk of dementia and Alzheimer’s disease.
Why is this thought to be the case? (1)
Due to docosahexaenoic acid (DHA) in fatty fish
(DHA is an omega-3 fatty acid)
Describe two pieces of evidence that support the fact that docosahexaenoic acid and omega-3 fatty acids may protect against developing dementia and Alzheimer’s disease. (2)
- Omega-3 supplements can be beneficial in early stages of Alzheimer’s
- High dose docosahexaenoic acid (DHA) supplement could be beneficial for carriers of the APOE4 gene before onset (or potentially in early stages) of Alzheimer’s
Give a group of patients who may particularly benefit from a high-dose docosahexaenoic acid (DHA) supplement before onset or in early stage Alzheimer’s disease. (1)
Carriers of APOE4 gene
Fill the gaps relating to omega-3, docosahexaenoic acid (DHA), and dementia. (4)
The benefits of DHA on cognition may be due to its ability to control ………………………. via its downstream products.
Three examples of these downstream products are: …………………….., ………………………….., and ……………………..
neuroinflammation
D-series resolvins
maresins
protectins
It is thought that DHA may benefit the brain and reduce the risk of dementia via its downstream products. One of which is neuroprotectin D1.
Describe the general effects of neuroprotectin D1 in terms of the following domains. (4)
a) neuronal death
b) brain cell survival
c) ageing
d) neurodegenerative disease
a) prevents neuronal death
b) improves brain cell survival
c) improves repair in ageing
d) improves repair in neurodegenerative diseases
It is thought that DHA may benefit the brain and reduce the risk of Alzheimer’s and dementia via its downstream products. One of which is neuroprotectin D1.
Give four effects of neuroprotectin D1 related to Alzheimer’s disease. (4)
- Reduces amyloid beta 42
- Represses inflammation
- Represses oxidative stress
- Represses apoptosis
***Last three are all usually induced by amyloid beta 42 (so does DHA reduce these by reducing Ab42?)
Give three mechanisms which Neuroprotectin D1, a downstream product of docosahexaenoic acid (DHA), may use to reduce amyloid beta 42 and protect against Alzheimer’s disease. (3)
- Upregulation of PPAR-gamma
- Upregulation of amyloid precursor protein alpha
- Downregulation of beta amyloid precursor protein
What is PPARy? (1)
A ligand-activated transcription factor, which can induce changes in gene expression and act as an anti-inflammatory factor.
What is the NOVA food classification system? (1)
Food classification which groups foods (into 4 groups) according to how processed the foods are.
Describe group 1 of the NOVA food classification system. (1)
Unprocessed/minimally processed foods such as fruit/veg/milk/meat/nuts/eggs
Describe group 2 of the NOVA food classification system. (1)
Processed culinary ingredients such as olive oil/butter/sugar/salt/honey/vinegar
Describe group 3 of the NOVA food classification system. (1)
Processed foods such as ham/cheese/fresh bread/bacon/salted nuts/tinned fruit in syrup/tinned tuna
Describe group 4 of the NOVA food classification system. (1)
Ultra processed foods such as supermarket bread/ready meals/breakfast cereal/biscuits/cakes/crisps
What is an ‘ultra processed food’? (3)
An industrially formulated edible substance
generated from compounds extracted/derived/synthesised from food, food substrates, or organic compounds
and contain 5 or more ingredients which are rarely/never used in home kitchens (for example artificial food additives).
Ultra processed foods make up more than half of the total dietary energy consumed in high income countries.
Give three reasons why this is. (3)
- Cheaper
- More palatable
- Longer shelf-life
Meta-analyses have found that higher consumption of processed food increases risk of developing what two neurological conditions in the future? (2)
Anxiety
Depression
Processed foods are thought to be particularly bad for health because they are energy rich, but lack nutritional components.
Give four ingredients in processed foods which make them energy rich, but don’t really have any nutritional value. (4)
- Refined starches
- Sugar
- Sodium
- Saturated and trans fats
Processed foods are thought to be particularly bad for health because they are energy rich, but lack nutritional components.
Give four nutritional components that are thought to be beneficial to health, but that are usually lacking in processed food. (4)
- Omega-3 fatty acids
- Fibre
- Polyphenols
- Minerals
Describe in general the mechanism by which artificial sweeteners and monosodium glutamate can affect the brain and mental health. (1)
Impact synthesis/release of DA, NA, and 5HT
Describe in general the mechanism by which dietary emulsifiers can affect the brain and mental health. (1)
Increased inflammation due to dysregulation of the gut microbiota
Describe the effect that aspartame is thought to have on the brain and mental health. (1)
Increased anxiety
A study investigating aspartame and its effects on the brain gave rodents either plain water, 0.03% aspartame (15% of FDA maximum daily dose), or 0.015% (8% of FDA maximal dose).
The open field test was carried out every 2 weeks for a few months.
What was the affect of aspartame on the open field test results? (1)
What does this indicate? (1)
Reduced time in centre for both doses
Indicates increased anxiety
A study investigating aspartame and its effects on the brain gave rodents either plain water, 0.03% aspartame (15% of FDA maximum daily dose), or 0.015% (8% of FDA maximal dose).
What was the effect of 0.015% aspartame on the elevated zero maze at 12 weeks? (1)
What does this indicate? (1)
Rodents showed less time in open arms with aspartame
This indicates increased anxiety
A study investigating aspartame and its effects on the brain gave rodents either plain water, 0.03% aspartame (15% of FDA maximum daily dose), or 0.015% (8% of FDA maximal dose).
They concluded that rodents that had received aspartame showed more anxiety on the open field test and elevated zero maze.
Suggest a way that you could confirm that the altered behaviour shown on the behavioural tests is due to increased anxiety. (1)
Give the rodents diazepam and look for reduced anxiogenic behaviours.
A study investigating aspartame and its effects on the brain gave rodents either plain water, 0.03% aspartame (15% of FDA maximum daily dose), or 0.015% (8% of FDA maximal dose).
One part of the study took the rodents that had received aspartame for 12 weeks and had them perform on the open field test twice, once with saline and once with diazepam (repeated measures).
Describe the results of this part of the study. (1)
Compare what was seen with aspartame+diazepam to what was seen with no aspartame. (1)
Give a short conclusion. (1)
Spent more time in centre of field with diazepam.
However still spent less time compared to rodents which had no aspartame.
Conclusion: diazepam can reduce aspartame-induced anxiety, however cannot fully ameliorate effect (animals will still have more anxiety than animals who never had aspartame).
A study investigating aspartame and its effects on the brain gave rodents either plain water, 0.03% aspartame (15% of FDA maximum daily dose), or 0.015% (8% of FDA maximal dose).
They found alterations in GABAergic and glutamatergic pathways in which part of the brain? (1)
Amygdala
A study investigating aspartame and its effects on the brain gave rodents either plain water, 0.03% aspartame (15% of FDA maximum daily dose), or 0.015% (8% of FDA maximal dose).
They found alterations in GABAergic and glutamatergic pathways in the amygdala at 12 weeks, by looking at gene expression related to these pathways.
Give three changes in gene expression that were seen with aspartame, relating to GABAergic and glutamatergic pathways. (3)
Upregulation of NMDA receptor subunit 2D (Grin2d gene)
Upregulation of metabotropic glutamate receptor 4 (Grm4 gene)
Downregulation of GABA-A receptor associated protein (Gabarap gene)
A study investigating aspartame and its effects on the brain gave rodents either plain water, 0.03% aspartame (15% of FDA maximum daily dose), or 0.015% (8% of FDA maximal dose).
They found that aspartame increases anxiety and alters GABAergic and glutamatergic neurotransmission.
Describe how this study tested whether the effect on anxiety was transgenerational. (1)
What were the results? (2)
- Test offspring for anxiety (this study tested 2 further generations), for example with open field test
- F1 and F2 generations showed less time in centre of open field test
- This was rectified by diazepam, which shows that the behaviour changes seen were due to anxiety
A study investigating aspartame and its effects on the brain gave rodents either plain water, 0.03% aspartame (15% of FDA maximum daily dose), or 0.015% (8% of FDA maximal dose).
They found that aspartame increases anxiety and alters GABAergic and glutamatergic neurotransmission, and that these effects were transgenerational.
Describe a drawback of this study concluding that the effects are transgenerational. (1)
Only tested paternal offspring (with anxiety passed down from Dad), so more replication is needed to confirm these effects.
What is the general role of dietary emulsifiers? (1)
Enable the homogenisation of immiscible substances
Give 2 product categories (other than food) where dietary emulsifiers may be used. (2)
- Cosmetics
- Pharmaceuticals
Give two general positive results of using dietary emulsifiers in food. (2)
- Improve texture
- Extend shelf-life
Give two examples of dietary emulsifiers. (2)
Carboxymethylcellulose (CMC)
Polysorbate-80 (P80)
Give five specific uses of the dietary emulsifier, carboxymethylcellulose, in specific foods. (5)
- Gives quality based texture and creamy mouthfeel in ice cream
- Regulates viscoelastic behaviour of fruit syrups and juices
- Used as a fat reducer in meat products
- Prevents layer formation and stabilises texture of acidic drinks at high/low temperatures
- Used as a thickening or dewatering agent in dairy products
Briefly describe the general effect of dietary emulsifiers on the brain and mental health. (1)
Increase anxiety
A study assessed the effects of dietary emulsifiers on the brain and mental health. They gave mice 1% of either carboxymethylcellulose (CMC) or polysorbate-80 (P80) in drinking water, or just plain water.
They tested the effects in both males and females.
Give the results for the open field test and the elevated plus maze. (2)
In males, CMC and P80 reduced time in centre of open field test.
This was not seen in females, or on the elevated plus maze.
A study assessed the effects of dietary emulsifiers on the brain and mental health. They gave mice 1% of either carboxymethylcellulose (CMC) or polysorbate-80 (P80) in drinking water, or just plain water.
They tested the effects in both males and females.
Describe how the emulsifiers affected amount of adipose tissue and spleen size in both males and females. (4)
Increased adipose tissue in males
Increased adipose tissue in females
Larger spleen in males
No change to spleen size in females
A study assessed the effects of dietary emulsifiers on the brain, body, and mental health. They gave mice 1% of either carboxymethylcellulose (CMC) or polysorbate-80 (P80) in drinking water, or just plain water.
They tested the effects in both males and females.
Give two general physiological changes that were seen in mice that had consumed dietary emulsifiers. (2)
- Increased adipose tissue (in males and females)
- Larger spleen (in males)
A study assessed the effects of dietary emulsifiers on the brain, body, and mental health. They gave mice 1% of either carboxymethylcellulose (CMC) or polysorbate-80 (P80) in drinking water, or just plain water.
They tested the effects in both males and females, and found that dietary emulsifiers increased the size of the spleen in males.
What might this indicate? (1)
Systemic inflammation
A study assessed the effects of dietary emulsifiers on the brain, body, and mental health. They gave mice 1% of either carboxymethylcellulose (CMC) or polysorbate-80 (P80) in drinking water, or just plain water.
They tested the effects in both males and females.
One of the tests looked at the preference for a novel mouse, as a measure of social interest.
Describe the results for both males and females. (2)
Why is interpreting and accurately drawing conclusions from this kind of data on social interactions difficult? (1)
Males - no effect on preference for novel mouse
Females - Decreased preference for novel mouse with dietary emulsifiers (so decreased social interest)
Difficult to interpret because female mice have different social interactions than male mice.
A study assessed the effects of dietary emulsifiers on the brain, body, and mental health. They gave mice 1% of either carboxymethylcellulose (CMC) or polysorbate-80 (P80) in drinking water, or just plain water.
They tested the effects in both males and females.
One test looked at the amounts of neuropeptides in the arcuate and paraventricular nuclei of the hypothalamus.
Give two neuropeptides which were shown to be affected. (2)
Agouti-related peptide
Alpha melanocyte stimulating hormone
A study assessed the effects of dietary emulsifiers on the brain, body, and mental health. They gave mice 1% of either carboxymethylcellulose (CMC) or polysorbate-80 (P80) in drinking water, or just plain water.
They tested the effects in both males and females.
One test looked at the amounts of neuropeptides in the arcuate and paraventricular nuclei of the hypothalamus.
Give the results regarding agouti-related peptide for both males and females. (2)
What is the usual role of agouti-related peptide? (1)
Males - increased agouti-related peptide
Females - no change to agouti-related peptide
Usually stimulates food intake and reduces anxiety
A study assessed the effects of dietary emulsifiers on the brain, body, and mental health. They gave mice 1% of either carboxymethylcellulose (CMC) or polysorbate-80 (P80) in drinking water, or just plain water.
They tested the effects in both males and females.
One test looked at the amounts of neuropeptides in the arcuate and paraventricular nuclei of the hypothalamus.
Give the results regarding alpha melanocyte stimulating hormone for both males and females. (2)
What is the usual role of alpha melanocyte stimulating hormone? (1)
Males - reduced aMSH
Females - reduced aMSH
would normally reduce food intake and increase anxiety
What are insecticides? (1)
Compounds that kill insects
Give three general uses of insecticides. (3)
(You can give an example if you can think of one)
- Crop protection
- Human health (stopping malaria spread etc)
- Veterinary use (tick/mite removal)
Describe the general, non-specific method by which insecticides kill pests. (1)
Target proteins involved in neurotransmission and muscle contraction
Complete the sentence relating to insecticides. (1)
Insecticides kill pests by interfering with the nervous system or muscle contraction. Many are based on ……………………………
natural neurotoxins
Describe why insecticides in the past were more harmful than they are now. (1)
What has changed to make them less harmful? (1)
They had negative effects on humans and non-pest animals as well as pests
However they are now designed with the intention of being pest-selective
Give three groups of pesticides which are older and confer a larger risk to humans and non-pest animals, so are no longer used. (3)
One of these groups has two specific examples/subgroups which are particularly dangerous. Name them. (2)
Organochlorines (DDT and cyclodienes)
Organophosphates
Carbamates
Fill the gaps relating to insecticides. (4)
Newer insecticides have good selectivity for their target ………………… in ……………………, and are relatively non-toxic to ………………….. and ……………………..
proteins
pests
humans
non-pest animals
Give an example of a newer insecticide which is more pest-selective and confers lower risk to humans and non-pest animals. (1)
Pyrethroids
Why are new types of insecticides being continually produced and brought onto the market? (1)
Insecticides tend to have a finite life span due to insects becoming resistant.
Give a few examples of types/groups of insecticides which are either used now or have been used in the past. (9)
- Organochlorines
- Organophosphates
- Carbamates
- Pyrethroids
- Phenylpyrazoles
- Neonicotinoids
- Diamides
- Butenolides
- Sulfoximines
Fill the gaps relating to insecticides. (2)
All types of insecticide target the nervous system except ………………………., which target …………………….
diamides
muscle
Give two types of insecticides which act on voltage-gated sodium channels. (2)
In addition, give a natural toxin which acts on this target, that the insecticides may be based upon. (1)
- DDT (which is an organochlorine)
- Pyrethroids
Pyrethrins are natural toxins which act on VGSCs.
Give two types of insecticides which act on the enzyme acetylcholinesterase. (2)
- Organophosphates
- Carbamates
Give three types of insecticides which act on nicotinic acetylcholine receptors. (3)
In addition, give a natural toxin which acts on this target, that the insecticides may be based upon. (1)
- Neonicotinoids
- Sulfoximines
- Butenolides
Nicotine is a natural toxin which acts at this target.
Give two types of insecticides which act on chloride channels on the post-synaptic membrane. (2)
- Organochlorides
- Phenylpyrazoles
Describe the exact target of the diamide insecticides in muscle. (1)
Ryanodine receptors on the sarcoplasmic reticulum
Describe the general effect of insecticides targeting and binding to voltage gated sodium channels. (1)
Binding to VGSCs stops it from inactivating
Describe the general effect of insecticides targeting and binding to the enzyme acetylcholinesterase. (1)
Prevents ACh breakdown, so higher synaptic ACh concentration
Describe the general effect of insecticides targeting and binding to nicotinic acetylcholine receptors. (1)
Binding causes activation of the nAChRs
Describe the general effect of insecticides targeting and binding to chloride channels. (1)
Prevents activation
Describe the general effect of insecticides targeting and binding to ryanodine receptors. (1)
Increased calcium release into cytosol
Give five specific targets that insecticides may bind to in order to kill pests. (5)
- Voltage gated sodium channels
- Acetylcholinesterase
- Nicotinic acetylcholine receptors
- Chloride channels
- Ryanodine receptors
Insecticides may exert their effects by targeting and binding to chloride channels on the post-synaptic membrane.
Describe a key difference between chloride channels found in invertebrates, and chloride channels found in vertebrates. (2)
In invertebrates, chloride channels are activated by glutamate
In vertebrates, chloride channels are activated by GABA
Pyrethroid insecticides are based around which naturally occurring neurotoxin? (1)
Pyrethrins
Pyrethrins are naturally occurring neurotoxins which can act as starting points for the development of some insecticides.
Name the plant that pyrethrins are derived from (common and scientific names). (2)
Pyrethrum daisy
Tanacetum cinerariifolium
Pyrethroid insecticides act on which target protein in the nervous system? (1)
Voltage gated sodium channels
Give three specific effects that pyrethroid insecticides have on voltage-gated sodium channels. (3)
- Sensitize channels to voltage
- Reduce inactivation (closing of inactivation gate)
- Prevent deactivation (closing of activation gate)
Do pyrethroid insecticides cause a gain or loss of function to voltage gated sodium channels? (1)
What is the overall consequence of the effect of pyrethroids on voltage gated sodium channels? (1)
Massive gain of function
Consequence is that the neurone is persistently depolarised (so cannot repolarise and produce more action potentials)
Describe the molecular mechanism of how pyrethroids are mostly selective for insects and not humans. (1)
Most of the selectivity can be traced back to a single amino acid difference between insect and human voltage gated sodium channels.
There have been some cases of farmers experiencing symptoms after using pyrethroid insecticides.
Give three symptoms experienced by farmers after using pyrethroids. (3)
Redness in skin
Tingling sensation
Burning pain in extremities
There have been cases where farmers using pyrethroid insecticides have complained of redness, tingling, and burning pain in their extremities.
Describe a piece of evidence relating to a medical condition with similar symptoms, which supports the fact that pyrethroids cause these symptoms.
Also, describe how this evidence may point to a mechanism of how pyrethroids might cause these symptoms. (4)
- Symptoms similar to those found in primary erythromelalgia (PE)
- PE caused by gain of function mutation in Nav1.7 channels
- which sensitises channels to voltage (meaning less depolarisation required for activation)
- So with the similarities in symptoms, it would be reasonable to assume that effects seen in farmers using pyrethroids may also be due to changes in or binding to Nav1.7 channels
It is thought that farmers using pyrethroids may experience symptoms such as burning pain in the extremities, due to the insecticide acting on Nav1.7 channels.
What is the Nav1.7 channel, and explain why changes to this channel may account for the symptoms seen in farmers. (2)
Subtype of human voltage gated sodium channel
Found in the PNS and associated with causing burning pain - so changes to channel may account for causing burning pain in extremities.
It is thought that symptoms seen in farmers after using pyrethroid insecticides (such as redness, tingling, and burning pain in extremities), may be due to the pyrethroids acting on Nav1.7 channels.
This is because similar symptoms are seen in a medical condition called Primary Erythromelelgia (PE), which is caused by a gain of function mutation in Nav1.7 channels.
Describe a more specific collection of evidence supporting the Nav1.7 channel in the toxicity of pyrethroids, again, linking the changes seen with pyrethroids to changes known to occur in PE. (3)
- Mutations seen in PE are commonly in the DIIS4-S5 linker, and DIIS5
- In insects, pyrethroid resistance mutations occur in similar places (eg. the M918T mutation, which occurs in DIIS4-S5 linker)
- This suggests that the DIIS4-S5 linker and the DIIS5 regions are regions of the VGSC where pyrethroids may bind to cause death in insects, and symptoms in humans
It is thought that symptoms seen in farmers after using pyrethroid insecticides (such as redness, tingling, and burning pain in extremities), may be due to the pyrethroids acting on Nav1.7 channels.
Give two specific molecular regions (ie. domains and segments) where pyrethroids may act on the VGSCs in both insects and humans. (2)
Describe one piece of evidence from humans, and one piece of evidence from insects, which supports these regions as important for pyrethroid binding. (2)
DIIS4-S5 linker
DIIS5
HUMAN EVIDENCE:
- These are the most common regions for mutations to be in primary erthyromelalgia, which causes similar symptoms to pyrethroid exposure
INSECT EVIDENCE:
- Common mutations which result in pyrethroid resistance occur in these regions
Experimental evidence supporting pyrethroids affecting human Nav1.7 channels include patch clamp experiments of TE671 cells.
Why are TE671 cells ideal for investigating Nav1.7 channels? (1)
They only express Nav1.7 channels
Experimental evidence supporting pyrethroids affecting human Nav1.7 channels include patch clamp experiments of TE671 cells.
Describe how this experiment could be carried out, including what could be measured. (4)
Activate channels at a range of depolarising voltage pulses
In the presence of different concentrations of different pyrethroids
Measure sensitivity to membrane potential (measure V50.act)
Also measure Tinact (how long inactivation takes) at a specific depolarising voltage
Experimental evidence supporting pyrethroids affecting human Nav1.7 channels include patch clamp experiments of TE671 cells.
In these experiments, V50.act was measured for different concentrations of pyrethroids.
Describe what is meant by V50.act in the context of pyrethroids acting on Nav1.7. (1)
Give an interpretation of V50.act (ie. what does a high/low number mean?). (1)
Membrane potential required to activate half of the available Nav1.7 channels on the cell.
Lower V50.act indicates a more excitable channel
Experimental evidence supporting pyrethroids affecting human Nav1.7 channels include patch clamp experiments of TE671 cells.
In these experiments, Tinact was measured for different concentrations of pyrethroids.
Describe what is meant by Tinact in the context of pyrethroids acting on Nav1.7. (1)
Give an interpretation of Tinact (ie. what does a high/low number mean?). (1)
Time constant describing how long it takes for currents to decay and the channel to inactivate.
Higher Tinact indicates a channel which stays open for longer.
Experimental evidence supporting pyrethroids affecting human Nav1.7 channels include patch clamp experiments of TE671 cells.
In these experiments, V50.act and Tinact were measured for different concentrations of different members of the pyrethroid group of insecticides.
In general, what would you expect to see for both V50.act and Tinact in the presence of pyrethroids? (2)
Lower V50.inact
Higher Tinact
Experimental evidence supporting pyrethroids affecting human Nav1.7 channels include patch clamp experiments of TE671 cells.
In these experiments, V50.act and Tinact were measured for different concentrations of different members of the pyrethroid group of insecticides.
Which of these measurements was changed more significantly in the presence of pyrethroids? (1)
V50.act
Experimental evidence supporting pyrethroids affecting human Nav1.7 channels include patch clamp experiments of TE671 cells.
In these experiments, V50.act and Tinact were measured for different concentrations of different members of the pyrethroid group of insecticides.
Which member of the pyrethroid group of insecticides particularly causes a change in these properties when added to a sample of TE671 cells? (1)
What changes are seen? (2)
Write a short conclusion explaining the effect of pyrethroids (particularly permethrin) on Nav1.7 channels in humans. (1)
Permethrin
- Lower V50.act
- Higher Tinact
Permethrin results in a more excitable channel which stays open for longer.
Experimental evidence supporting pyrethroids affecting human Nav1.7 channels include patch clamp experiments of TE671 cells.
As well as measuring V50.act and Tinact, tail currents were measured in the presence of different concentrations of different members of the pyrethroid insecticide family.:
- Permethrin
- Deltamethrin
- Cypermethrin
- Tau-flu
Describe the tail currents seen in the presence of these pyrethroids (not taking into account concentrations). (4)
State what was seen in the normal ‘control’ conditions without any pyrethroids added. (1)
Relatively large and long-lasting tail currents seen with DELTAMETHRIN, CYPERMETHRIN, TAU-FLU.
No tail currents with PERMETHRIN.
No tail currents in control groups without pyrethroids added.
Experimental evidence supporting pyrethroids affecting human Nav1.7 channels include patch clamp experiments of TE671 cells.
As well as measuring V50.act and Tinact, tail currents were measured in the presence of different concentrations of different members of the pyrethroid insecticide family.:
- Permethrin
- Deltamethrin
- Cypermethrin
- Tau-flu
With some of these pyrethroids, large and long-lasting tail currents were seen. What are these tail currents indicative of? (1)
Ion channels closing more slowly
Experimental evidence supporting pyrethroids affecting human Nav1.7 channels include patch clamp experiments of TE671 cells.
As well as measuring V50.act and Tinact, tail currents were measured in the presence of different concentrations of different members of the pyrethroid insecticide family.:
- Permethrin
- Deltamethrin
- Cypermethrin
- Tau-flu
Describe the concentration-dependency of the tail currents seen in the presence of these molecules. (1)
The pyrethroids which showed larger and longer-lasting tail currents (DELTAMETHRIN, CYPERMETHRIN, TAU-FLU) acted in a concentration-dependent manner (higher dose = larger tail current).
Fill the gaps relating to insecticides and their effects on humans. (5)
Human Nav1.7 shows sensitivity to ……………………….. at relatively low concentrations.
There is a ………………………. shift in V50.act, ……………………. inactivation, and we also see ……………………….. when looking at the action potential profile.
These features all indicate ………………………………….
pyrethroids
negative
slowed
tail currents
increased excitability
Give three electrophysiological findings supporting pyrethroids acting on Nav1.7 channels in humans. (3)
IN PRESENCE OF PYRETHROIDS, NAV1.7 SHOWS…
- Lower V50.act (increased excitability)
- Higher Tinact (longer inactivation)
- Tail currents
It is thought that farmers get symptoms such as redness, tingling, and burning due to pyrethroid insecticides acting on Nav1.7 channels.
However, not all farmers get these symptoms.
Describe a theory which would explain why only some farmers experience these symptoms. (3)
- Some farmers could also have mutations in Nav1.7 channel
- Like mutations seen in primary erythromelalgia (which causes similar symptoms)
- Leading to a synergistic effect of mutation + pyrethroids and the appearance of symptoms
Give two natural toxins from which neonicotinoid insecticides are developed. (2)
- Nicotine
- Epibatidine
Name the plant that produces nicotine as a natural insecticide (common and scientific name). (2)
Tobacco plants
Nicotiana tabacum
Epibatidine is a natural neurotoxin produced in the environment, which may act as a starting point for developing insecticides.
How is epibatidine produced in the environment? (1)
What target does it act on? (1)
Produced by Epipedobates tricolour frogs
Acts on nicotinic ACh receptors
What target protein do neonicotinoid insecticides act on in the nervous system? (1)
Describe briefly (one word) how neonicotinoids affect this protein. (1)
Nicotinic acetylcholine receptor
Agonists
True or false? Explain your answer if appropriate. (1)
Neonicotinoid insecticides are very selective for insect acetylcholinesterase, so they do not pose much risk for humans.
False - they are very selective for insect NICOTINIC ACH RECEPTORS
They do not act on AChE, but the rest is true, they are very selective
Fill the gaps relating to neonicotinoid insecticides. (5)
Neonicotinoids act as …………………… at nicotinic ACh receptors.
Because ………………………. cannot break down neonicotinoids like it does with ACh, there is a large ……………….. of function at AChRs because they are persistently ……………………..
This leads to the organism becoming ………………………
agonists
acetylcholinesterase
gain
activated
paralysed
Give three reasons why neonicotinoids are particularly effective to use as insecticides. (3)
- Resistance is slow to develop
- They are systemic (incorporate into whole plant)
- Can be applied through seed treatment
Neonicotinoids are very effective insecticides, and one reason for this is because they can be applied through seed treatment.
Describe how insecticides are applied through seed treatment and why this is effective. (4)
- Treat seeds with insecticide
- Insecticide distributes throughout plant during growth
- So the whole plant is covered
- And target insects are killed when they feed on the plant
Give two advantages and one disadvantage of insecticides like neonicotinoids being applied through seed treatment. (3)
ADVANTAGES:
- Whole plant is covered
- No indiscriminate spraying
DISADVANTAGE:
- Also incorporates into pollen so can affect pollinators such as honeybees
Seed treatment with insecticides such as neonicotinoids can affect honeybees by getting into the plant’s pollen.
Describe a legislation which has aimed to protect pollinators such as honeybees from insecticides such as neonicotinoids. (1)
EU enforced ban of some neonicotinoids in 2013
Apart from honeybees, there is some concern that other beneficial invertebrates may be at risk from neonicotinoid insecticides.
Give two examples of beneficial invertebrates which may be at risk. (2)
- Earthworms
- Leeches
(Both come under ‘annelid’ category)
There is some concern that neonicotinoid insecticides may be a danger to annelids such as earthworms and leeches.
An experiment aimed to test whether annelid muscle nAChRs are sensitive to neonicotinoids. They used a leech muscle contraction assay, with 2 neonicotinoids (imidacloprid, acetamiprid) and 1 butenolide (flupyradifurone).
What would be seen on a control assay when increasing concentrations of ACh are added? (1)
Step-wise contractions with increasing concentrations of ACh
There is some concern that neonicotinoid insecticides may be a danger to annelids such as earthworms and leeches.
An experiment aimed to test whether annelid muscle nAChRs are sensitive to neonicotinoids. They used a leech muscle contraction assay, with 2 neonicotinoids (imidacloprid, acetamiprid) and 1 butenolide (flupyradifurone).
What would be seen on a control assay when increasing concentrations of ACh are added in the presence of eserine? (1)
Why would this be seen? (1)
Step-wise contractions which begin at lower concentrations of ACh, than when ACh is added without eserine.
Eserine is an acetylcholinesterase inhibitor so keeps ACh in the synapse/NMJ for longer
There is some concern that neonicotinoid insecticides may be a danger to annelids such as earthworms and leeches.
An experiment aimed to test whether annelid muscle nAChRs are sensitive to neonicotinoids. They used a leech muscle contraction assay, with 2 neonicotinoids (imidacloprid, acetamiprid) and 1 butenolide (flupyradifurone).
What would be seen on muscle contraction assays with these three insecticides? (1)
HINT: Same effect is seen for all three
How could we prove that the effects seen were due to activation of the nAChR? (1)
Step-wise muscle contractions with increasing concentrations (this begins at relatively low concentrations of insecticide)
Contractions gradually reduce with addition of increasing concentrations of a competitive nAChR antagonist
There is some concern that neonicotinoid insecticides may be a danger to annelids such as earthworms and leeches.
An experiment aimed to test whether annelid muscle nAChRs are sensitive to neonicotinoids. They used a leech muscle contraction assay, with 2 neonicotinoids (imidacloprid, acetamiprid) and 1 butenolide (flupyradifurone).
All of these insecticides caused muscle contractions.
Describe how the ‘strength’ of the effects seen with the insecticides compare to the following situations. (2)
a) If just ACh was added to muscle
b) If ACh + Eserine was added to muscle
Write a short sentence to conclude the effects of insecticides on the nAChR and muscle contraction. (1)
a) effects of insecticides were stronger than just adding ACh
b) effects of insecticides were weaker than with ACh+Eserine
Insecticides have a strong agonistic effect on nAChRs, causing a strong muscle contraction.
There is some concern that neonicotinoid insecticides may be a danger to annelids such as earthworms and leeches.
An experiment aimed to test whether annelid muscle nAChRs are sensitive to neonicotinoids. They used a leech muscle contraction assay, with 2 neonicotinoids (imidacloprid, acetamiprid) and 1 butenolide (flupyradifurone).
The insecticides caused strong muscle contractions at relatively low concentrations.
Describe whether the insecticides would be considered full agonists or partial agonists, and explain why. (2)
Full agonists
because they produce the same maximal response as ACh
***However, imidacloprid produced a larger Rmax, so could be considered more than a full agonist
Fill the gaps relating to neonicotinoid insecticides. (3)
Neonicotinoids cause substantial ………………………….. in annelids (leeches, earthworms) at relatively low concentrations.
…………………….. insecticides work in the same way.
Like in pests/target insects, the molecular mechanism of the insecticides is …………………………..
muscle contraction
butenolide
agonising the nAChR
Give two next steps when investigating and mitigating the effect of neonicotinoid insecticides on beneficial invertebrates like annelids (leeches and earthworms). (2)
- Limit treatment with neonicotinoids to seeds
- More testing of other beneficial invertebrates may be useful
