Of particular interest is brain-derived neurotrophic factor (BDNF), one of the most abundant neurotrophic factors in the brain. BAY 73-4506 clinical trial altered neural plasticity in response to stress Recent reports have demonstrated altered molecular and cellular responses

to stress and have contributed to the hypothesis that altered neural plasticity contributes to stress-related psychiatric illnesses. Some examples of stress responses are discussed in this section. Stress alters learning and memory Stress is known to significantly influence learning and memory, and the effects are dependent on Inhibitors,research,lifescience,medical the type, duration, and intensity of the stressor. Emotional arousal can enhance learning and memory via synaptic plasticity of amygdala-dependent pathways, and this Inhibitors,research,lifescience,medical is thought to be the basis for intense, long-term memories of traumatic events and posttraumatic stress disorder.4,5 However, stress can also impair subsequent learning and memory and can even lead to amnesia.6 The influence of stress on hippocampal-dependent learning is complex and dependent on the type of learning task. In studies of LTP, a consistent suppression of neural plasticity is observed after exposure Inhibitors,research,lifescience,medical to stress or adrenal glucocorticoids.6,7 In one of these studies, the suppression of LTP was observed after exposure to an uncontrollable

stressor and correlated with behavioral Inhibitors,research,lifescience,medical performance in a learning and memory task. Giving the animals control over the stress (ie, the stress could be terminated) did not lead to reduced LTP or decreased learning and memory.8 A role for BDNF in the actions of stress on LTP has also been suggested.9 For additional references and discussion of the effects of stress on learning and memory, see the reviews in references 4 to 7. Stress causes atrophy of hippocainpal neurons One of the best-characterized examples of altered structural Inhibitors,research,lifescience,medical plasticity in response to stress is the atrophy of hippocampal neurons, which was first described by McEwen and colleagues (Figure 1.).10 They found that repeated restraint stress results in atrophy of the

dendrites of CA3 pyramidal neurons in the hippocampus, measured as a decrease in the number and length of apical dendrites.11 The reduction in dendritic arborization was found to be dependent on find more long-term, repeated exposure to restraint stress (3 weeks) and to be reversible when the animals are removed from stress. The atrophy of CA3 pyramidal cells appears to result from the elevation of adrenal glucocorticoids that occurs during stress because chronic administration of corticosteronc, the active form in rodent, results in a similar decrease in number and length of dendrites.12 The actions of stress and glucocorticoids are blocked by administration of an NMDA receptor antagonist, indicating that this glutamate receptor is required for atrophy of CA3 neurons.