Distribution and regulation of proteins related to neuronal degeneration

Jamieson, Elizabeth Ann (1997) Distribution and regulation of proteins related to neuronal degeneration. PhD thesis, University of Glasgow.

Abstract

Using in situ hybridisation, Tau 1 and Tau 2 gene expression has been studied in adult and neonatal rats in the basal forebrain and hippocampal regions. Tau 1 mRNA levels are significantly higher in the neonatal (gestation day 17) rats, with Tau 2 mRNA levels being significantly higher in the adult rats (Chapter 3). Using in situ hybridisation, Tau 1 and Tau 2 gene expression in the basal forebrain and hippocampal regions has been studied in adult rats in response to intraperitoneal administration of the following compounds: ondansetron (100ng/kg), MK801 (1mg/kg), GYKI52466 (30mg/kg), indomethacin (5mg/kg) and aniracetam (l0mg/kg). None of the compounds cause a significance change in either Taul or Tau 2 mRNA levels after a 24 hour period (Chapter 3). Glial cell cultures have been used to study the distribution and expression of NADPH diaphorase expression in response to exposure of the cells to cytokines, excitatory amino acid agonists and pro teases. The glial cultures have been characterised by positive staining to glial fibrillary acidic protein and NADPH diaphorase. Points 3-5 summarise the work carried out using these cultures (Chapter 4). Lipopolysaccharide (100mug/ml) significantly increases NADPH diaphorase staining. A maximum induction is observed after a 6 hour time period. Interleukin-1 (0.25ng/ml) also significantly increases NADPH diaphorase staining, and again maximum induction occurs after a 6 hour time period. The lipopolysaccharide-induced increase in NADPH diaphorase staining remains unaltered following combined exposure of the cells to lipopolysaccharide (100mug/ml ) and the calmodulin anatgonist W7 (400muM). The excitatory amino acid agonists glutamate (50muM), AMPA (50muM) and NMDA (50muM and 100muM) significantly increase NADPH diaphorase staining. This induction occurs after a 24 hour time period. The inhibitors APV (100muM) and CNQX (100muM) reduce the glutamate and AMPA-induced increase in NADPH diaphorase staining to near control values, again after a 24 hour time period. The glutamate-induced increase in NADPH diaphorase staining is reduced following combined exposure of the cells to glutamate (50muM) and the calmodulin antagonist W7 (400muM). Exposure of the cells to the proteases chymotrypsin (300ng/ml) and trypsin (500ng/ml) increase NADPH diaphorase staining. This induction occurs after a 24 hour time period. This increase is reduced to near control levels following combined exposure of the cells to the proteases and their respective inhibitors chymostatin (100muM) and trypsin inhibitor (l?/ml), again after a 24 hour time period. 6\ Basal forebrain primary cultures have been used to study the distribution and expression of cytoskeletal proteins and NADPH diaphorase staining following exposure of the cells to nitric oxide, excitatory amino acid agonists and cytokines. The cells have been characterised by positive immunostaining to choline acetyltransferase (ChaT), neuron specific enolase, neurofilament and microtubule-associated protein 2 (MAP2). Points 6-10 summarise the work carried out using these cultures (Chapter 5). (Abstract shortened by ProQuest.).

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Neurosciences.
• Colleges/Schools: College of Medical Veterinary and Life Sciences
• Supervisor's Name: Sirinathsinghji, Dr. Dalip
• Date of Award: 1997
• Depositing User: Enlighten Team
• Unique ID: glathesis:1997-71731
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 17 May 2019 09:31
• Last Modified: 08 Sep 2022 13:20
• Thesis DOI: 10.5525/gla.thesis.71731
• URI: https://theses.gla.ac.uk/id/eprint/71731