Impact of prenatal stress on hippocampal neuroplasticity

  • 葉 哲銘

Student thesis: Doctoral Thesis


The environment in early life can have a major impact on later life Extensive evidence from animal and human studies suggests that maternal stress may impede normal brain development and functions of their offspring A significant number of stress exposed offspring show selective impairments of attention arousal and information processing which appear early in lifetime and later go on to develop into major cognitive deficits and affective disorders later in life Although the biological consequence and underlying mechanisms by which prenatal stress exposure causes the cognitive deficits remain essentially unknown it has been proposed to be the results of alterations in the anatomical organization or function of the hippocampus a brain region critically involved in the control of cognitive functions The overall hypothesis to be evaluated is that exposure to stress in utero alters synaptic plasticity in the hippocampus and these aberrant regulations may result in maladaptive changes in neural circuitry that enhance the risk of developing psychopathology later in life We found that the prenatal stress on the impact of the offspring came from the change of synaptic plasticity without effects on the growth curve Electrophysiological recording on hippocampal CA1 brain slices from prenatal stressed offspring showed impairment in the induction of long term potentiation (LTP) However the induction of long term depression (LTD) was prolonged to express in 5-weeek-old offspring by prenatal stress The induction of LTD by metabotropic glutamate receptor (RS)-3 5-dihydroxyphenylglycine (DHPG) was not affected by prenatal stress By separating different subcellular fractionation the expression of NMDA receptor subunit NR1 NR2A NR2B showed no significant difference between prenatal stress and control group Notably we found that prenatal stress induced a significant increase in the levels of pro-BDNF and the decrease in the levels of tissue plasminogen activator (tPA) These results suggest that an inhibition of the converting process of pro-BDNF to mBDNF may be account at least in part to the effect of prenatal stress on the subsequent induction of hippocampal synaptic plasticity in later life Although we did not observe a role for epigenetic regulation of tPA gene in the effect of prenatal stress on tPA expression However the phosphorylation of CREB (p-CREB) binding to tPA promoter was decreased in PS-treated rats by ChIP assay and associated mechanism needs further experiment to elucidate Understanding the biochemical substrates and the underlying mechanisms of the cognitive deficits induced by prenatal stress exposure will facilitate the development of more effective intervention strategies target these pathways to treat mental illnesses
Date of Award2014 Aug 1
Original languageEnglish
SupervisorKuei-Sen Hsu (Supervisor)

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