Excitotoxcity and neurotoxicity

Question 1

when dose excitotoxcity occur

Answer 1

Excitotoxicity occurs when excessively high levels of the neurotransmitter glutamate act on ionotropic and metabotropic receptors resulting in depolarisation, Ca2+ influx and thus more glutamate release
Ultimately this leads to cell death as mitochondrial function is disrupted resulting in ATP depletion and the production of reactive oxygen species

Question 2

what is the process of neurotransmission

Answer 2

neurotransmitter molecules are packaged into membranous vesicles in presynaptic terminal. when the membrane depolarises by voltage gated calcium to open the increase in intracellular calcium triggers fusion. Transmitter is then released into extracellular space in quanta sized amounts and diffusions passively across cleft. Some bien to post and activated receptors trigger even on G protein cascade. Eventually cleared by continued diffusion, enzymatic degradation or active uptake into cells.

Question 3

example of excitatory neurotransmitters

Answer 3

Glutamate (Glu) Acetylcholine (ACh) Histamine Dopamine (DA) Norepinephrine (NE); also known as noradrenaline (NAd) Epinephrine (Epi); also known as adrenaline (Ad)

Question 4

examples of inhibitory neurotransmitters

Answer 4

Inhibitory neurotransmitters gamma-Aminobutyric acid (GABA) Serotonin (5-HT) Dopamine (DA)

Question 5

glutamate is a major excitatory neurotransmitter but can cause excitotoxicity resulting in calcium overload. what is one line of defence against this

Answer 5

mitochondrial metabolism

Question 6

neurones exposed to excessive glutamate show what

Answer 6

cell swelling
dendritic beading
ROS
ion dyshomeostasis

mitochondira distress cause ca move in and apoptosis and cell death

Question 7

what cells prevent excitotoxicity

Answer 7

astrocytes

Question 8

what ion overload increase ROS production causing mitochondrial damage

Answer 8

calcium

Question 9

what are neuropeptides and why are they different to neurotransmitters

Answer 9

Neuropeptides may be a subtype of neurotransmitters

larger 
released more slowly ( 50ms compared to 0.1ms) 
last longer 
can act at distal sites 
cannot be re-uptjaane for reuse

Question 10

examples of neuropeptides

Answer 10

vasopressin 
cholecystokinin 
endorphins 
somatostatin 
ACTH/MSH

Question 11

example of neruotrasnitters

Answer 11

glutamate
asparate
serotonin ACH
GABA

Question 12

what is long term potentiation

Answer 12

Long-term potentiation (LTP) is a process involving persistent strengthening of synapses that leads to a long-lasting increase in signal transmission between neurons.

Question 13

organophosphate poisoning uses ACH what are the symptoms

Answer 13

bradycardia
SLUDGE
salivation, lacrimation, urination, diarrhea, GI upset, emesis

DUMBELS (diaphoresis and diarrhea; urination; miosis; bradycardia, bronchospasm, bronchorrhea; emesis; excess lacrimation; and salivation

Question 14

benzodiazepine overdose - caused by like lorazepam uses what neurotrnamsiiter and what effects

Answer 14

GABA = GABAa receptor

large pupil s
respiratorydepression
agitation and cyanosis and tremors and confusion

Question 15

difference between the two gaba receptors

Answer 15

There are two classes of GABA receptors: GABAA and GABAB. GABAA receptors are ligand-gated ion channels (also known as ionotropic receptors); whereas GABAB receptors are G protein-coupled receptors, also called metabotropic receptor

Question 16

opioid overdose can causes bradypnoea and pinpoint pupils what neurotransmitter is used in this case

Answer 16

opiates such as endorphins

Question 17

depression uses what neurotransmitter

Answer 17

serotonin

sleep deprivation , low self-esteem , no pleasure in activities

Question 18

phenyl ketone urea PKU is an excess of the neurotransmitter phenylalanine which is a precursor for dopamine, melanin. what symptoms

Answer 18

musty odor 
seizures 
itnellectual disability 
eczema , repeatedly sick 
fairer skin and tantrums

Question 19

neurotoxins are destructive to nervous tissue and can be endogenous or exogenous what are some examples

Answer 19

tetanus toxin, heavy metals such as arsenic

leads to excitotoxicity

Question 20

define excitotoxicity

Answer 20

Over-excitation of neurons can lead to toxicity, and cell death

Usually safe chemicals (e.g. glutamate, NMDA) cause toxicity
Caused by prolonged high-levels that cause cellular damage
This is associated with a variety of diseases

Question 21

in usual health glutamate bind to receptors. Calcium enters the cell from outside, and from the ER. Sodium enters the cell, allowing more Calcium to enter (via Na+/Ca2+ exchangers. This triggers depolarisation, which inhibits glutamate resorption (increases extracellular glutamate). Calcium is stored (buffered) in the ER and mitochondria, and then actively pumped back out of the cell. This requires energy

what happens in excitotoxity

Answer 21

excessive glutamate binding causes excessive calcium influx so cell is unable to expel it quickly enough so build up in the mitochondria.

this high calcium causes further glutamate releasee. as well as this proteases and lipase are activated by the Ca causing increased permability. NO synthase requires Ca so more NO which is neurotoxic at high levels.
It also increases arachidonic acid release which increased free radical ad inflammatory mediator production.
Ca build up in mitochondria impairing function
more reactive oxygen species created by dysfunctional mitochondria, increasing cellular damage.

PGE2 and PGD2 are produced from arachidonic acid and cause inflammation

Question 22

a cell exposed to excessive glutamate will present with

Answer 22

beading axons and swollen cell body

Question 23

how can an ischaemic brain injury causes exctitoxicty

Answer 23

no oxygen means mitochondria dysfunction so ca build up.

Question 24

in Parkinson excitotoxicity is implicated in destruction of pigmented cells of substantial nigra

ALS - form of motor neurone disease uses riluzole to slow progression and seems to increase gultamate uptake

in alzeihers memantine slows progression and blocks what channels

Answer 24

NMDA glutamate

Question 25

what cells absorb glutamate

Answer 25

glial cells - failure would result in excitotoxicity

atrocytes convert it into ATP