Repeated restraint stress suppresses neurogenesis and induces biphasic PSA‐NCAM expression in the adult rat dentate gyrus

Abstract

Chronic restraint stress has been shown to induce structural remodelling throughout the interconnected dentate gyrus-CA3 fields. To find out how this stressor affects the rate of adult hippocampal neurogenesis, we subjected rats to acute or chronic restraint stress and assessed the proliferation, survival and differentiation of newly born cells in the dentate gyrus. We also examined polysialylated neural cell adhesion molecule expression, a molecule normally expressed in immature neurons and important for morphological plasticity. The results show that acute restraint stress did not change either the proliferation of dentate gyrus precursor cells or the expression of polysialylated neural cell adhesion molecule, whereas 3 weeks of chronic restraint stress suppressed proliferation by 24% and increased polysialylated neural cell adhesion molecule expression by 40%. The study was extended for an additional 3 weeks to trace the survival and development of the cells born after the initial 3 weeks of restraint. Rats subjected to 6 weeks of daily restraint stress exhibited suppressed cell proliferation and attenuated survival of the recently born cells after the extended time course, resulting in a 47% reduction of granule cell neurogenesis. Furthermore, 6 weeks of chronic stress significantly reduced the total number of granule cells by 13% and the granule cell layer volume by 5%. Expression of polysialylated neural cell adhesion molecule followed a biphasic time course, displaying a significant up-regulation after 3 weeks of daily restraint stress that was lost after 6 weeks of stress. These studies may help us understand the basis for hippocampal shrinkage and raise questions about the ultimate reversibility of the effects of chronic stress.

Exposure to Stressors during Juvenility Disrupts Development-Related Alterations in the PSA-NCAM to NCAM Expression Ratio: Potential Relevance for Mood and Anxiety Disorders

“…However, acute restraint procedures, which failed to induce hippocampal structural alteration, also failed to increase polysialylation of NCAM (Pham et al, 2003). To the best of our knowledge, our study presents the first evidence of a persistent increase in expression levels of totalPSA-NCAM following a nonchronic stress procedure.…”

Personality traits in rats predict vulnerability and resilience to developing stress-induced depression-like behaviors, HPA axis hyper-reactivity and brain changes in pERK1/2 activity

“…An increasing number of animal models based on stress interventions have been shown to effectively mimic a variety of psychopathological alterations (Willner, 2005;Renthal et al, 2007;Stam, 2007;Ilin and Richter-Levin, 2009). In both animals and humans, excessive and/or enduring stress has been found to cause structural and neurochemical alterations in several brain structures, especially in the hippocampus (Lupien et al, 1998;Sheline et al, 1999;McEwen, 2000;Pham et al, 2003;Bisaz et al, 2011), the prefrontal cortex (Drevets et al, 1997;Rajkowska, 2000;Holmes and Wellman, 2009) and the amygdala (Sandi et al, 2008;Mitra et al, 2009;Roozendaal et al, 2009).…”

ROCK2 regulates bFGF-induced proliferation of SH-SY5Y cells through GSK-3β and β-catenin pathway

“…Neurogenesis in DG is decreased in adult rodent models for stress-related disorders (Gould et al, 1997;Malberg et al, 2003;Pham et al, 2003). The administration of drugs commonly used in treatments of stress-related disorders increase neurogenesis in DG of adult rodents (Chen et al, 2000;Malberg et al, 2000;Hao et al, 2004).…”