Transcriptomic analysis of neuroprotective pathways in astrocytes and the effect of prosaposin on astrocyte culture

  • Anastasia Neimane

Student thesis: Master's ThesisMaster of Science by Research (MScR)

Abstract

Astrocytes are glial cells in the CNS that play a vital role in health and disease. Prosaposin and its putative receptors GPR37 and GPR37L1 have been shown to exert neuroprotective effect in various animal disease models. In vitro studies have shown that prosaposin and one of the receptors on expressed astrocytes are sufficient for glioprotection and neuroprotection as demonstrated by scratch wound assay and LDH cytotoxicity assay following application of hydrogen peroxide, rotenone or staurosporin; astrocytes and neurons were further co-cultured and experiments repeated to perform RNA-Seq and acquire separate astrocytic and neuronal transcriptomes for different experimental conditions: astrocytes alone in prosaposin-depleted media, astrocytes alone in prosaposindepleted media with added TX14(A), astrocytes co-cultured with stressed neurons, stressed neurons, unstressed neurons. These transcriptomes were analysed to describe cellular and molecular events during addition of TX14(A) to astrocyte culture, application of an oxidative stressor to neuronal culture and co-culturing astrocytes and pre-stressed neurons. Coculturing stressed neurons with astrocytes lead to upregulation of pro-survival pathways MAPK, Wnt, and PI3K-Akt and the following genes that code for neuroprotective secreted molecules were upregulated in astrocytes: Il11, Osm, Ngf, Bmp7, Postn, Sema3a, Lif, Col3a1, Tgfb1.
Date of Award23 Mar 2021
Original languageEnglish
Awarding Institution
  • University of Bristol
SupervisorSergey Kasparov (Supervisor) & Anja G Teschemacher (Supervisor)

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