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Title: The regulation of hippocampal neurotrophin gene expression by sub-toxic glutamatergic and cholinergic agonists
Author: French, S. J.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 1998
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Limbic seizures induced by kainic acid can regulate the level of neurotrophin gene expression in the adult rat hippocampus. I investigate whether non-toxic infusions of glutamatergic or cholinergic agonists that were minimally seizure-behaviourally active can also alter neurotrophin gene expression in the male rat. Stereotaxic intra-ventral hippocampal microinfusions were made of 0.5μ AMPA, carbachol, nicotine and pilocarpine. Animal behaviour was observed for 2 hours post infusion, and was quantified on a scale of limbic seizure activity. After 7 days hippocampal tissue from one group of animals was processed for semi-thin plastic sections, and cell densities calculated using an unbiased disector method. After various survival times, brains from other groups were evaluated by in situ hybridisation using 35sulphur labelled oligonucleotide and ribo-probes for the mRNA of the following genes: NGF; BDNF; NT-3; TrkA; TrkBl; TrkB2; TrkB3 and TrkC. Gene expression levels were measured as optical density values using an NIH image analysis system. AMPA (0.5 nmol), carbachol (3.3 nmol), nicotine (17.3 nmol) and pilocarpine (6 nmol) regulated neurotrophin gene expression at doses that did not cause cellular damage or behavioural apparent seizures. NGF was increased by all agonists, the time course of nicotine differed from the other drugs. The nicotine regulation of NGF was suppressed by the action of glutamatergic antagonists, NK-801 and NBQX. BDNF was only regulated by AMPA and pilocarpine. NT-3 and TrkA were generally depressed by all agonists at earlier time points. The TrkB receptors are all positively regulated by the agonists. These findings suggest sub-toxic activation of glutamate or cholinergic systems can alter hippocampal neurotrophin expression, that there maybe an interaction between the nicotine and glutamatergic systems, and that this regulation may take in the physiology of the septal-hippocampal system.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available