Long-term effects of chronic unpredictable mild stress on cell adhesion molecules NCAM and L1 in the regulation of behaviour in C57BL/6J mice

Abstract

Chronic stress induces depression-like behaviour in mice and simultaneously induces a pattern of changes in the expression of the cell adhesion molecules NCAM and L1 which correlates with the role of these molecules in the synaptic plasticity and neuroprotective mechanisms. In this context, dysregulations in NCAM and L1 gene expression are also implicated in stress-related psychiatric diseases like major depressive disorder, bipolar disorder and schizophrenia. This study was designed to investigate the short- and long-term (2 and 14 days after termination of chronic unpredictable mild stress) effects of a new chronic unpredictable mild stress protocol (CUMS) generated to resemble non-traumatic stress conditions in humans, on mouse behaviour and the expression of the mRNA for the cell adhesion molecules NCAM and L1. Analyses of behaviour (depression-like behaviour and anxiety), physiological parameters (body weight and weight of adrenal glands, preputial gland, testes and spleen), plasma corticosterone concentration as well as hippocampal mRNA expression of NCAM, L1 and the corticosteroid receptors MR and GR in C57BL/6J adult male mice were performed. Analyses on short-term effects showed chronic stress-induced depression-like behaviour, a hypertrophy of adrenal glands, a decrease in the weights of preputial glands and body weight. Moreover, the plasma cortoicosterone release was dysregulated 2 and 14 days after chronic unpredictable mild stress. On the contrary chronic unpredictable mild stress-induced alterations on depression-like behaviour and body weight normalized 14 days after chronic unpredictable mild stress exposure. At long-term we saw a reduction in mRNA expression levels of NCAM and mineralocorticoid receptor (MR) in the hippocampus whereas neither glucocorticoid receptors (GR) nor L1 mRNA expression were changed at short- and long-term following chronic unpredictable mild stress protocol. Summarising up, we created a chronic stress protocol which induced significant short-term and long-term behavioural, physiological and molecular responses in mice. Moreover we observed a recovery of behaviour and body weight in C57BL/6J adult male mice to unstressed levels following the long-term termination of the chronic unpredictable mild stress.