Stress, sex, hippocampal plasticity: relevance to psychiatric disorders

Abstract

Studies of the hippocampus as a target of stress and sex hormones have revealed a considerable degree of structural plasticity and remodeling in the adult brain that differs between the sexes. These sex differences, as well as stress sensitivity, may be programmed by events early in life, including the developmental actions of gonadal, thyroid and adrenal hormones. Two forms of hippocampal structural plasticity are affected by stress. First, repeated stress causes remodeling of dendrites in the CA3 region. Second, different modalities of stress suppress neurogenesis of dentate gyrus granule neurons. In addition, ovarian steroids regulate synapse formation during the estrous cycle of female rats. All three forms of structural remodeling of the hippocampus are mediated by hormones working in concert with excitatory amino acids (EAA) and NMDA receptors. EAA and NMDA receptors are also involved in neuronal death that is caused in pyramidal neurons by seizures and ischemia, and by severe and prolonged psychosocial stress. Clinical MRI studies have shown that there is atrophy of the hippocampus in a number of psychiatric disorders, as well as during aging in some individuals, accompanied by deficits in declarative, episodic, spatial and contextual memory performance. It is, therefore, important to appreciate how hippocampal dysfunction may play a role in the symptoms of the psychiatric illness and, from a therapeutic standpoint, to distinguish between a permanent loss of cells and a reversible atrophy in order to develop treatment strategies to either prevent or reverse deficits. In addition, remodeling of neural tissue may occur in other brain regions, such as the amygdala and prefrontal cortex.