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Objective To investigate the effect of running exercise on depression-like behaviors in chronic unpredictable stress (CUS)-induced depression mice and GABAergic interneurons, PV+ interneurons and ratio of GAD67+/PV+ cells in medial prefrontal cortex (mPFC). Methods After mouse model of depression was successfully established through CUS, these male C57BL/6 mice aged 4~6 weeks were randomly divided into control group, CUS control group and CUS+running group according to the results of sucrose preference test. The behaviors of the 3 groups were evaluated with sucrose preference test, forced swimming test and tail suspension test. The mRNA expression levels of GAD1, GAD2, PV and CCK in mPFC of mice were detected using qRT-PCR. The number of GABAergic interneurons and PV+ interneurons in mPFC of mice were quantified using immunohistochemical assay and unbiased stereological technique, and the ratio of PV+/GAD67+ cells was calculated. Results Compared with those in CUS control group, the mice from the CUS+running and control groups showed a significantly higher percentage of sucrose preference (P0.05). The mRNA level of PV, number of PV+ interneurons and ratio of PV+/GAD67+ cells in mPFC were remarkably lower in the CUS group than the CUS +running group and control group (P

N-Methyl-d-aspartate receptor (NMDAR) signaling pathway has been implicated in the pathogenesis and treatment of depression. However, the role of NMDAR subunits in depression is still unclear. In this study, alteration in all seven NMDAR subunits in several brain areas of rats exposed to chronic unpredictable mild stress (CUMS), an animal model of depression, was detected. Our findings demonstrated that: (1) CUMS could induce a reduction in sucrose preference, an indicator of typical depression-like behaviors; (2) CUMS significantly reduced the NMDAR subunits of GluN2B and GluN3 in the medial prefrontal cortex (mPFC), but not altered all seven NMDAR subunits in hippocampus and corpus callosum of rats; (3) subunit composition of NMDARs in corpus callosum was different from that in mPFC, PFC and hippocampus; and (4) the mRNA expressions of GluN2B, GluN3A and GluN3B in mPFC as well as mRNA expression of GluN2C in corpus callosum were correlated to sucrose preference in rats. These findings suggested that GluN2B and GluN3 in mPFC may contribute to the pathophysiology of depression.

The effects of nitric oxide (NO) on cerebral capillary angiogenesis and the regulation of pro- and anti-angiogenic factors that affect cerebral capillary angiogenesis, spatial learning, and memory ability are unclear. We assessed the effects of the NO precursor L-arginine (L-ARG) and the NO synthesis inhibitor Nω-nitro-L-arginine methylester (L-NAME) on cortical capillaries and spatial learning and memory abilities. We administered intracerebroventricular injections of L-ARG or L-NAME to rats before they were evaluated in the Morris water maze. We measured the levels of NO synthase activity, pro-angiogenic factors, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF-2), and the expression of the anti-angiogenic factors angiostatin and endostatin. We also quantitatively investigated parameters of the cortical capillaries using immunohistochemistry and stereological methods. The L-ARG treatment significantly improved rats' spatial learning abilities and increased NOS activity in the cortex. L-NAME disrupted spatial learning. Following the L-ARG treatment, the expression of the pro-angiogenic factors (VEGF and FGF-2) was higher and the expression of anti-angiogenic factors (endostatin) was lower than the vehicle-treated animals. In contrast, the L-NAME treatment reduced the expression of VEGF and increased the expression of endostatin. Based on these results, modulation of the NO content in the brain regulates VEGF, FGF-2, and endostatin expression, as well as capillary parameters in the cortex, which in turn influence spatial learning and memory performance.