Psychopharmacology 3 Flashcards

Question

What role does APP have in tau in AD

Answer 1

APP intensifies tau pathology which causes its spread throughout the brain in a chain reaction

Answer 2

Trans-entorhinal cortex Entorhinal cortex Hippocampus Temporal pole Inferior temporal cortex Mid-temporal cortex Polymodal association areas Secondary sensory or motor cortex Primary sensory and motor cortex All neocortical areas and many subcortical nuclei

Answer 3

Tau can be introduced into hippocampal neurons for vivo and in vitro studies using Polymeric alkylpyridinium salts (PAPs) Exogenous tau does not cause major distruption but phosphorylation causes congitive deficit and reduced LTP Those with Tau, PAPs and okadaic acid were significantly longer in swim studies. Histology - PAPs (showed no tau), PAPs and tau (delivered tau well into neurons), triple (extends into distal dendrites) Therefore - confirmed that hyperphosphorylation of tau is crucial for neuronal malfunction

Answer 4

Prevention of protein aggregation or fibre dissolution

Answer 5

Previously existing models are often limited in their translational value due to Tau overexpression, and the frequent occurrence of motor deficits which prevent comprehensive behavioural assessments.

Answer 6

demonstrated early emerging (~6months) phenotypes of heightened anxiety in the elevated plus maze, depressive/apathetic behaviour in a sucrose preference test and generally reduced exploratory activity in the absence of motor impairments. Investigations of cognitive performance indicated prominent dysfunctions in semantic memory, as assessed by social transmission of food preference, and in behavioural flexibility during spatial reversal learning in a home cage corner-learning task. Spatial learning was only mildly affected and task-specific, with impairments at 12months of age in the corner learning but not in the water maze task.

Answer 7

Impaired learning (determined by latency, distanced traveled, errors and hole deviation errors) whilst less likely to use spatial search strategy to find the escape hole in the barnes maze compared to wild type mice. Shows this mice type have impaired visuo-spatial learning and memory at 16 months of age.

Answer 8

Possible AD risk using anaesthesia - Anaethetised the mice twice a week for 3 months with isoflurane. Showed - ong lasting reduced exploratory behavior, increased Aβ aggregates and high molecular weight peptides. This was not present in WT mice.just alzheimer model mice (AβPPswe mice)

Answer 9

Treatment with NMDA antagonist, MK801 (0.05 mg/kg, i.p.) for 13 days significantly prevented OKA-induced changes I.E - increased mRNA and protein expression of Tau, Ca2+/calmodulin-dependent protein kinase II (CaMKII), Calpain and GSK3β in the hippocampus and cerebral cortex. These results infer that NMDA antagonist MK801 and memantine are effective against OKA-induced neurotoxicity. Therefore, the present study clearly indicates the involvement of NMDA receptor in OKA (ICV)-induced Tau hyperphosphorylation.

Answer 10

GLUK2 KO showed - Anxiety was recorded in the elevated plus maze, social behavior in a three-chamber apparatus, and cognition in different water maze protocols. Deletion of the GluK2 gene reduced locomotor activity and sociability as indicated by the social interaction task. GluK2 KO mice learnt to locate a hidden platform in a water maze surrounded by a curtain with hanging cues faster than wild-type mice. They maintained a bias toward the target quadrant when some of these cues were removed, at which point wild-types orthogonalized the behavior and showed no memory. Shows that - glutamatergic dysfunction underlying a number of social- and cognition-related phenotypes relevant to ASD.