The relationships among neuropeptide, calcitonin gene-related peptide (CGRP), and memory formation remain unclear. Here, we showed that the intracerebroventricular administration of CGRP impaired the traumatic fear memories, in a widely studied animal model of post-traumatic stress disorder. We found that CGRP administration suppressed fear memory by increasing neuronal PAS domain protein 4 (Npas4), phosphorylated histone deacetylase 5 (HDAC5), and protein kinase D (PKD). We also discovered that Npas4 knockdown inhibited CGRP-mediated fear memory. CGRP decreased the binding between HDAC5 and the Npas4 enhancer site and increased the binding between acetylated histone H3 and the Npas4 enhancer site. The pharmacological inhibition or knockdown of PKD attenuated the CGRP-mediated impairment of fear memory and the increased phosphorylation of HDAC5 and Npas4 expression. Our findings demonstrated that the CGRP-PKD pathway was associated with the histone H3 acetylation-Npas4 pathway. These results suggested a novel function for CGRP on fear memory, through epigenetic regulation.

Calcitonin gene-related peptide (CGRP) plays an important role in several physiological processes such as vasodilation, cardiovascular homeostasis and transmission of pain. Here we report the generation of a transgenic mouse overexpressing αCGRP and the impact of this on baseline physiological responses. αCGRP transgenic mice displayed significantly increased αCGRP mRNA levels in the kidney, heart and hippocampus. To assess cardiovascular physiology, we measured arterial pressure using a tail cuff system. Heart rate, systolic pressure, mean arterial pressure and diastolic pressure were significantly lower in αCGRP transgenic mice than wild-type mice. To assess pain, a hot plate test was performed and the latency of response was used as an indicator of supraspinal response. In addition, a tail immersion test was performed to assess thermal nociception. A significant increase in latency was observed in the αCGRP transgenic mice when compared with wild-type mice in both tests. These results suggest that αCGRP overexpression causes an increase in thermal reaction and downregulation of the cardiovascular system, presumably due in increased levels of αCGRP.

Although chronic ethanol treatment is known to impair learning and memory, humans commonly consume a range of alcoholic beverages. However, the specific effects of some alcoholic beverages on behavioral performance are largely unknown. The present study compared the effects of a range of alcoholic beverages (plain ethanol solution, red wine, sake and whiskey; with a matched alcohol concentration of 10%) on learning and memory. 6-week-old C57BL6J mice were orally administered alcohol for 7 weeks. The results revealed that red wine treatment exhibited a trend toward improvement of spatial memory and advanced extinction of fear memory. Additionally, red wine treatment significantly increased mRNA levels of brain-derived neurotrophic factor (BDNF) and N-methyl-D-aspartate (NMDA) receptors in mice hippocampus. These results support previous reports that red wine has beneficial effects.

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【Objective】 Calcitonin gene-related peptide (CGRP) is a neuropeptide consisting of 37 amino acids produced by splicing difference from the calcitonin, and has strong vasodilation. We have shown that the expression of CGRP was significantly decreased in depression-like model mice hippocampus. CGRP administration into the mice brain before the beginning of stress exposure, normalized the behavioral dysfunction with increase never growth factor. In the present study, we investigated the role of highly CGRP expressing gene steadily using CGRP over expressing, CGRP transgenic (Tg) mice. 【Methods】 8 weeks to 9 weeks old CGRP (Tg) mice were used. Same age of C57BL/6J mice were used as the control group. Behavioral tests were conducted on open field test, forced swimming test (FST), tail suspension test (TST) and sucrose preference test to evaluate depression-like behavior. 【Results】 Immobility time in the FST and TST in CGRP Tg mice were significantly longer than C57BL/6J mice. In contrast, in the sucrose preference test, which measures anhedonic-like deficits, there were no significant differences. Furthermore, in the open field test, which measures spontaneous behavior decreased in CGRP Tg mice. These results suggest that prolonged immobility time of CGRP Tg mice is not due to depressive symptoms, but spontaneous behavior may have an effect.