Novel treatment strategies, including NMDA selleck chemicals llc receptor antagonists, could act via reversal of these synaptic deficits. Stress and depression cause neuronal atrophy and loss: circuit-specific
effects Among the findings of altered brain structure and function in depression, the most consistent is reduced volume of the PFC and hippocampus (Figure 1).11,12 Reduced volume Inhibitors,research,lifescience,medical is inversely correlated with length of illness, time of treatment, and severity of depression. Postmortem studies also demonstrate reduced neuronal cell body size, atrophy of processes, and a reduction of glia in PFC.13-15 Although ultrastructural studies, such as spine synapse analysis, have been difficult in postmortem tissue, a recent report demonstrates a decrease in the number of synapses in the PFC in a small cohort of depressed subjects.16 Findings in rodent models have extended the human studies, Inhibitors,research,lifescience,medical and confirm that exposure to chronic stress, like depression, causes atrophy and loss of neurons and glia in the PFC and hippocampus, Inhibitors,research,lifescience,medical which could contribute to the decreased volume reported in patients.3,13,17,18 The atrophy of neurons is characterized by a decrease in the number and length of dendrite branches, as well as a decrease in the density of spine synapses.18-20 Figure 1. Chronic stress causes
neuronal atrophy: a decreased number of spine synapses. Basic research studies demonstrate that repeated stress causes atrophy of neurons in the prefrontal cortex and hippocampus of rodents. Shown on the left is a diagram of a segment … In contrast to the atrophy Inhibitors,research,lifescience,medical observed in PFC and hippocampus, stress causes hypertrophy of neurons in the amygdala, which could contribute to increased emotional valence and anxiety in depression.21 Hypertrophy and increased function of amygdala could
result from atrophy and decreased function Inhibitors,research,lifescience,medical of PFC, as this region provides inhibitory control of amygdala and could thereby contribute to depressive symptoms. Similarly, atrophy and decreased function of PFC neurons could contribute to abnormal function of other aspects of the depression circuit (eg, increased activity of basal ganglia and subcallosal cingulate cortex). Stress decreases neuronal and glial Ketanserin proliferation In addition to decreased neuronal arborization and synapse number, stress also exerts a significant impact on the birth of new neurons and glia. Acute and chronic stress decreases neurogenesis in the dentate gyrus of adult hippocampus.22 There have also been several studies of cell proliferation in the hippocampus of postmortem depressed subjects, although there is no evidence to date of decreased neurogenesis, indicating that loss of neurons does not contribute to depression.23 Rather, these postmortem studies have reported that depressed patients treated with antidepressants have increased levels of newborn cells in the hippocampus.