Morphological changes CT99021 induced by 100 nM CORT were smaller than those induced by 10 nM CORT. The majority of spines had a distinct head and neck, therefore these analysis cover major populations of spines. In the current study, we clarified the complete pathway for corticosteroid synthesis ��PREGRPROGRDOCRCORT�� in hippocampal neurons. We demonstrated for the first time the expression, neuronal localization and activity of P450 in the hippocampus. In addition, the localization of P450 , another enzyme participating in DOC synthesis, was demonstrated. The expression of P450 in the hippocampus has been described in several studies and neuronal localization of P450 has been demonstrated using immunohistochemistry . We observed the localization of P450 in cell bodies of pyramidal and granule neurons at mRNA and protein level. Gomez-Sanchez and co-workers observe a weak CORT production from 3H-DOC, roughly 0.4 pmol/mg/3 h in the hippocampus . However, they doubted de novo synthesis of CORT from PROG since CORT levels in whole brain were nigligible after adrenalectomy of rats . According to their report, CORT in the whole brain of five ADX rats was below the detection limit, but four ADX rats had measurable CORT in the brain . Therefore, their results do not completely eliminate a possibility of the presence of brain-CUDC-907 synthesized CORT. It should be noted that the expression level of P450 in the hippocampus does not change upon ADX . In the hippocampus of ADX rats we observed the direct conversion of DOC to CORT as well as low, but physiologically significant level of CORT. The expression of P450 in neurons supports endogenous synthesis. Interestingly, the expression level of P450 is roughly 10-fold more in the cortex than in the hippocampus. The low nanomolar level of CORT, synthesized in the hippocampal neurons, may play a essential role in enhancement of synaptic plasticity, in contrast to the deleterious effects elicited by micromolar plasma CORT secreted from the adrenal gland under stressful conditions . In the current study, low dose CORT enhanced spinogenesis, particularly increasing the density of small-head spines . It has been previously demonstrated that nanomolar doses of CORT drives the Erk MAP kinase pathway, increasing both the expression and phosphorylation of MAP kinase . Taken together, hippocampus- synthesized CORT might induce spinogenesis via activation of the Erk MAP kinase pathway.