Extreme stress is closely linked with symptoms of depression. Chronic social stress can cause structural and functional changes in the brain. These changes are associated with dysfunction of neuroprotective signalling that is necessary for cell survival, growth, and maturation. Reduced neuronal numbers and volume of brain regions have been found in depressed patients, which may be caused by decreased cell survival and increased cell death. Elucidating the mechanism underlying the degeneration of the neuroprotective system in social stress-induced depression is important for developing neuroprotective measures. The Repressor Element 1 Silencing Transcription Factor (REST) also known as Neuron-Restrictive Silencing Factor (NRSF) has been reported as a neuroprotective molecule in certain neurological disorders. Decreased expression levels of REST/NRSF in the nucleus can induce death-related gene expression, leading to neuronal death. Under physiological stress conditions, REST/NRSF over expression is known to activate neuronal survival in the brain. Alterations in REST/NRSF expression in the brain has been reported in stressed animal models and in the post-mortem brain of patients with depression. Here, we highlight the neuroprotective function of REST/NRSF and discuss dysregulation of REST/NRSF and neuronal damage during social stress and depression.
Exposure to endocrine-disrupting chemicals may adversely affect animals, particularly during development. Tris(1,3-dichloroisopropyl) phosphate (TDCIPP) is an organophosphate with anti-androgen function in vitro that is present in indoor dust at relatively high concentrations. In male rats, androgens are necessary for the development of reproductive organs, as well as the endocrine and central nervous systems. However, we currently do not know the exact effects of TDCIPP exposure through suckling on subsequent reproductive behavior in males. Here, we show that TDCIPP exposure (25-250 mg kg-1 via oral administration over 28 consecutive days post-birth) suppressed male sexual behavior and reduced testes size. These changes were dose-dependent and appeared first in adults rather than in juveniles. These results demonstrate that TDCIPP exposure led to normal body growth and appearance in juveniles, but disrupted the endocrine system and physiology in adults. Therefore, assays should be performed using adult animals to ensure accuracy, and to confirm the influence of chemical substances given during early mammalian life.