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.

Numerous rodent models of depression have been reported, most requiring a long experimental period and signiˆcant eŠort. We explored a new potential mouse model for depression by investigating whether exposure to a 15-day chronic stress paradigm could induce depression-like behavior in ICR mice. Animals in the stress-exposed groups were subjected to 3 h of restraint while immersed in a 28°C water bath daily for 15 consecutive days. Immobility time in the forced swim test was increased in the chronic stress-exposed mice compared with the controls. Serum corticosterone levels were also much higher in the stressed mice than in the control mice. Hippocampal cell survival (BrdU-positive cells) and neurotrophic factor (NGF, TrkA) mRNA levels were signiˆcantly decreased in the chronic stress-exposed mice compared with controls. Administration of the anti-depressant drugs clomipramine (20 mg/kg/d) or imipramine (30 mg/kg/d) did not change the immobility time in the forced swim test, but treatment with lithium (100 mg/kg/d) did result in slight improvement. These results suggest that this 15-day chronic stress paradigm can induce depression-like behavior and neurological changes, in a short time and with minimal eŠort, facilitating the assessment of treatments for depression.

Atherosclerosis is driven by inflammatory reactions that are shared with the innate immune system. Calcitonin gene related peptide (CGRP) is a potent vasodilator peptide and it is widely distributed in central and peripheral nerve. Recent studies have shown that CGRP can be produced by immune cells such as macrophages following stimulation. However, it is unclear whether CGRP is involved in atherosclerosis development. Here, we investigated whether CGRP has a role in the development of atherosclerosis in apolipoprotein E-deficient (apoE-/-) mice. Newly generated double-knockout apoE-/-/CGRP-/-mice and control apoE-/-mice were fed a high-fat diet from 5 to 10-week-old. ApoE-/-/CGRP-/-mice demonstrated exacerbated atherosclerotic lesion severity with increase total cholesterol level. As a potential mechanism accounting for plaque progression in ApoE-/-/CGRP-/-mice, macrophage migration or adhesion was further investigated and only migration was significantly increased by CGRP depletion. These results suggest that CGRP deletion exacerbated atherosclerosis in apoE-/-mice. Macrophages migration was identified as potential mediators of this effect.

【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.

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