These cell layers and their connections (mossy fiber pathway and Schaffer collateral) have long been used as cellular models of learning and memory (ie, LTP). However, it is clear that stress and glucocorticoids also influence the survival and plasticity of neurons in other brain regions (such as PFC, vide infra) that have not yet been studied in the same detail as the hippocampus. Dendritic remodeling of hippocampal neurons is one of the best-characterized effects of stress on cellular morphology23,24 Dendritic remodeling is deeply observed in the CA3 pyramidal neurons as atrophy-decreased number

and length of the apical dendritic branches. This stress-induced atrophy of CA3 neurons results after 2 to 3 weeks of exposure Inhibitors,research,lifescience,medical to restraint stress or more long-term social stress, and has been observed in rodents and Inhibitors,research,lifescience,medical tree shrews.23,24 Although the effects of chronic stress in the CA3 layer tend to be most pronounced, slight structural changes are also found in the CA1 and dentate gyrus following a 1-month multiple stress paradigm.25 Profound alterations

in mossy fiber terminal morphology and significant synapse loss have also been described. The hippocampus has a very high Small molecule library cell line concentration of glutamate and expresses both glucocorticoid (GR) and mineralcorticoid (MR) corticosteroid receptors, though these may be relatively scarce in the hippocampus of primates,26,27 and more prevalent in cortical Inhibitors,research,lifescience,medical regions. MR activation in the hippocampus (CA1) is associated with reduced calcium currents, while GR activation leads to increased N-methyl-D-asparate (NMDA) receptor throughput and increased calcium currents that could predispose to neurotoxicity. Inhibitors,research,lifescience,medical In fact, increasing

evidence implicates glutamatergic neurotransmission in stress-induced hippocampal atrophy and death. Histopathological changes in rat PFC after corticosterone Inhibitors,research,lifescience,medical administration have recently been described although this area has not been as comprehensively studied as the hippocampus. Using a Golgi-Cox procedure, Wellman28 examined pyramidal neurons in layers 3-mercaptopyruvate sulfurtransferase II and III of the medial PFC, quantifying dendritic morphology in three dimensions. In this study, he demonstrated a significant rearrangement of apical dendrites in corticosterone-treated animals, with an increase in the dendritic material proximal to the soma and a decrease in distal dendritic material. This suggests that stress may result in a significant reorganization of the apical dendritic arbor in medial PFC in rats. It is noteworthy that glucocorticoids may exert deleterious effects on neural plasticity and morphology, since a significant percentage of mood disorder patients show some form of HPA axis activation. It has been hypothesized that the depressive subtypes most, frequently associated with HPA activation are also the most likely to be associated with reductions in hippocampal volume.