Prenatal stress alters hippocampal synaptic plasticity in young rat offspring through preventing the proteolytic conversion of pro-brain-derived neurotrophic factor (BDNF) to mature BDNF

Che Ming Yeh, Chiung Chun Huang, Kuei Sen Hsu

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73 Citations (Scopus)

Abstract

Prenatal stress (PS) has been associated with a higher risk of development of various neurological and psychiatric disorders later in life, but the underlying mechanisms are not yet fully understood. Here, using a chronic prenatal restraint stress model where the rat dams were immobilized for 45 min three times per day during the last week of pregnancy, we explored the long-lasting effects of PS on hippocampal synaptic plasticity in the offspring of both sexes. We found that PS switched the direction of synaptic plasticity in hippocampal CA1 region, favouring low-frequency stimulation-induced long-term depression (LTD) and opposing the induction of long-term potentiation (LTP) by high-frequency stimulation in young (5-week-old) rat offspring, but these changes disappeared at adult age (8 weeks old). Fostering of PS offspring to control dams did not alter the effects of PS on LTP and LTD. In addition, PS-induced changes in LTP and LTD induction were correlated with increasing endogenous pro-brain-derived neurotrophic factor (pro-BDNF) and decreasing of the mature form of BDNF (mBDNF) levels. Furthermore, PS resulted in a significant decrease in the activity and expression of tissue plasminogen activator (tPA), a key serine protease involved in the extracellular conversion of pro-BDNF to mBDNF. No significant differences were observed between the sexes for the effects of PS on hippocampal synaptic plasticity, the levels of pro-BDNF and mBDNF, and tPA expression. These results suggest that PS downregulates tPA levels within the hippocampus, inhibiting the proteolytic conversion of pro-BDNF to mBDNF, thereby leading to long-lasting alterations of the properties of synaptic plasticity.

Original languageEnglish
Pages (from-to)991-1010
Number of pages20
JournalJournal of Physiology
Volume590
Issue number4
DOIs
Publication statusPublished - 2012 Feb

All Science Journal Classification (ASJC) codes

  • Physiology

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