Glutamate signalling Flashcards
what are the functions of glutamate apart from being a major NT in CNS?
- synaptic organisation
- neuronal migration
- neuron variability
Glutamate has signalling role in non-CNS tissue
True or False
True, has signalling roles in other tissues; bone, testis, pancreas, hormonal system and gut but the glutamate cannot cross the BBB hence its synthesis from glutamine takes place locally
glutamate is synthesised from what?
glutamate is synthesised from glutamine (in the presence of glutaminase)
what is the role of astrocyte in the excitatory synapse?
Astrocytes carries out recycling of glutamate
what type of receptors are glutamate?
ionotropic and metabotropic
what is the action of glutamate in the neutrons?
- Ca2+, Na+, Zn2+ influx
- K+ efflux
- also plays important role in plastic changes associated with learning, memory and neuronal development
- involved in LTP which in turn induces dendritic spine growth
name the three glutamate receptor agonists?
NMDA, AMPA and kainate
what is the function of the three glutamate agonists?
- NMDA receptors – Ca2+ influx related to synaptic plasticity important in learning and memory
- AMPA – plasticity and synaptic transmission, particularly LTP
- Kainate - synaptic plasticity
name which cells are responsible for these glutamate transporters?
- EAAT1,EAAT2
- EAAT3
- EAAT4
- EAAT5
- EAAT1,EAAT2, astrocytes and microglia
- EAAT3 cerebral neurons
- EAAT4 cerebellar neurons
- EAAT5 retinal
L- glutamate has toxic effect on inner layer of retina
True or False
True
name the diseases in which excitatoxicity is implicated?
- ischaemia
- AD
- PD
- HD
- ALS
- often late onset - suggests, ageing is a factor
how does the cell death take place in excitatoxicity
via
- membrane breakdown
- cytoskeletal alterations
- NO derived free radicals
what factors other than glutamate contribute to the excitotoxicity?
- ROS and RNS
- Ca2+ influx -> oxygen radicals and NO
- peroxynitrite generation and cell damage
what is the association b/w excitatoxicity and parkinsons?
- normally, balance b/w striatal activation through NMDA R and inhibition through D2 receptors
- however, there is dopaminergic cells -> glutamatergic overactivity and change in NMDA subunits
- therefore, PD treatment - NMDA antagonists tried in animal models -> showed reduced parkinsonian findings however, not well tolerated in primate -> hallucinations and sedatives
what is the association b/w excitatoxicity and AD?
- glutamate: could be major executor of neuronal damage in AD
- ## amyloid beta and tau - associated with glutamate and activation of NMDA R -> enhances production of these beta and tau
