Part 4 Flashcards
ROS increase with age. Inflammatory cytokines then bind to the cell membrane and then…
it turn on transduction systems which leads to genetic transcription. This leads the production of i NOS and COX – 2. This leads to increased inflammation which then causes a feedback loop to cause more cytokine production
How does inflammation leads to inflammatory prostaglandins?
It increases free radical reactive oxygen and nitrogen species (ROS & RNS). This then turns on “death genes”. This leads to stimulation of inducible nitric oxide synthase (iNOS) and Cox 2 enzymes which helps convert arachidonic acid to inflammatory prostaglandins
Three main reasons that diabetes is bad for the brain
1) glycated proteins produced 50 times the ROS compared to non-glycated ones.
2) hippocampus is damaged by glucose
3) beta-amyloid can be modified by glucose to be more inflammatory which then turns on microglia
Normal mitochondrial function leads to normal ATP production which maintains the Intracellular and extra cellular gradient how?
It helps to maintain a normal NMDA receptor magnesium block
Abnormal mitochondrial function leads to decreased ATP production which leads to an abnormal gradient which leads to a poor magnesium/NMDA receptor block. This then leads to what?
An influx of calcium via glutamate binding at the receptor. This calcium then damages the mitochondria which leads to decreased ATP production which then continues the cycle
Do Alzheimer’s patients have increased inflammatory cytokines?
Yes
Mitochondrial dysfunction leads to increased cytokine production which activates what enzyme?
iNOS which increases nitrogen oxide production which then reacts with superoxide and forms peroxy nitrite which then leads to cell toxicity and thus inhibited mitochondrial function
A concussion causes impaired axonal transport via what?
The end disruption of neurofilament and microtubules
A concussion causes neuronal membrane damage at the cellular level. What happens next?
There are ionic shifts which then leads to increased extracellular glutamate and aspartate (mediated by astrocytes and microglia). This then may cause some cellular apoptosis
Supplementing what 2 vitamins has been shown to decrease the risk of Alzheimer’s by as much as 78%?
Vitamins C and E
Increased BMI is associated with what later in life?
Decreased hippocampal volume
High sugar diets, insulin dysregulation and production of AGEs strongly implicated in what?
CNS inflammation and neuronal calcium channel dysregulation
There is a direct link between what and atrophy of the medial temporal lobes?
Diabetes
True or false: diabetes impairs executive function?
True
What are the percentage increase risks for Alzheimer’s disease with Apo E 3/4 and 4/4?
3/4 = 45% increased risk 4/4 = 90% increased risk
In the brain ApoE is mainly secreted by what?
Astrocytes and microglia, both of which surround amyloid plaques
Astrocytes promote beta-amyloid clearance via what?
An ApoE dependent mechanism
Lower levels of omega-3 fatty acids correlated with what in regard to the brain?
Smaller brain volumes and worst performance on cognitive testing. Brains also age faster.
Omega-3 fatty acids do what do cerebral blood flow?
Increase it
High omega-3 fatty acid levels correlates with what Alzheimer’s markers?
Lower plasma beta-amyloid 40 and 42
In relation to Alzheimer’s disease, people with the highest DHA consumption had what?
A 78% decrease risk reduction for Alzheimer’s disease
DHA plays an important role in what 6 functions?
1) mitochondrial and neuronal membrane fluidity
2) Signal transduction
3) Neurogenesis
4) Gliogenesis
5) Synaptogenesis
6) Reduction of the Cox-2 enzyme
Neuronal DHA does what to phosphatidylserine and phosphatidylethanolamine?
It increases their levels
Neuronal DHA does what during development and adulthood?
It promotes neurite outgrowth
What is curcumin and can it cross the blood brain barrier?
It is the principal curcuminoid of Tumeric and it can cross the blood brain barrier because it is lipophilic
What does curcumin do in TBI patients?
It inhibits interleukin 1 beta and NF kappa beta. It also decreased post traumatic reactive gliosis and prevents up regulation of aquaporin 4 which therefore decreases edema
True or false. Diets rich in curcumin are associated with a lower incidence of Alzheimer’s disease?
True
What does curcumin do in in vitro studies about Alzheimer’s disease?
It inhibits amyloid beta aggregation and inflammation. It also inhibits beta secretase and acetylcholinesterase
How could curcumin help in Parkinson’s disease?
It prevents the clumping of alpha synuclein
Coffee drinking midlife is associated with what later in life?
Decrease risk of dementia and Alzheimer’s disease
A mouse study showed that caffeine did what in regards to Alzheimer’s disease?
It inhibited amyloid beta production
In a French study, three servings or greater of caffeine showed what?
Better verbal retrieval and better visual spatial memory. This was seen in women but not men
In an animal study of Resveratrol, what was shown that would help with Alzheimer’s disease?
It was protective of beta-amyloid induced neurotoxicity by suppressing nitric oxide synthase production
True or False: Parkinson’s disease patients have reduced levels of glutathione
True
Three facts about Parkinson’s disease and l-dopa
1) patients need higher doses over time
2) L-dopa does not change progression of the disease
3) L-dopa increases risk for vascular disease and elevates homocystine
What are the seven most common causes of mild cognitive impairment, Alzheimer’s disease and related disorders?
1) degenerative brain disease, Alzheimer’s disease, Parkinson’s disease and Louis body dementia
2) vascular disease and strokes
3) cancer and side effects of cancer treatments
4) trauma
5) infections and immune disease
6) alcohol and other Brain toxins
7) Disorders causing metabolic encephalopathy, depression, thyroid disease and diabetes
What are the seven functions of the prefrontal cortex?
Impulse control, attention, organization, self-monitoring, self-control, critical thinking and empathy
What are the seven functions of the temporal lobes?
Hearing, reading, reading social cues, short-term memory, recognizing objects by sight, mood stability and naming
What are the eight functions of the parietal lobes?
Direction, sensory perception, seeing motion, visual guidance (grabbing objects), recognizing objects by touch, ability to know where you are in space, knowing your right from your left and reading and creating maps
What are the four functions of the occipital lobes?
Site, color perception, lines and depth
What are the nine problems with prefrontal cortex damage?
Poor judgment, impulsivity, short attention span, disorganization, trouble learning from experience, confusion, poor time management, repeated mistakes and lack of empathy
What are seven symptoms of temporal lobe damage?
Memory loss, word finding difficulties, trouble reading social cues, mood instability, poor visual recognition, abnormal sensory perception and religious or moral preoccupation
What are seven symptoms of parietal lobe damage?
Impaired direction sense, left right confusion, trouble dressing or putting things together, denial of illness, trouble with math or writing, neglect and impaired copying drawing or cutting
