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Calcitonin gene-related peptide pre-administration acts as a novel antidepressant in stressed mice.

Hashikawa-Hobara N, Ogawa T, Sakamoto Y, Matsuo Y, Ogawa M, Zamami Y, Hashikawa N - Sci Rep (2015)

Bottom Line: Serum corticosterone levels, hippocampal proliferation and mRNA expression of neurotrophins were measured.Although intracerebroventricular CGRP administration (0.5 nmol) did not alter depression-like behavior after 15-day stress exposure, a single CGRP administration into the brain, before the beginning of the 15-day stress exposure, normalized the behavioral dysfunctions and increased nerve growth factor (Ngf) mRNA levels in stressed mice.These results suggest that CGRP expression in the mouse hippocampus is associated with depression-like behavior and changes in Ngf mRNA levels.

View Article: PubMed Central - PubMed

Affiliation: Department of Life Science, Okayama University of Science, 1-1 Ridai-cho, Kita-ku, Okayama 700-0005, Japan.

ABSTRACT
Calcitonin gene-related peptide (CGRP) is a neuropeptide that has potent vasodilator properties and is involved in various behavioral disorders. The relationship between CGRP and depression-like behavior is unclear. In this study, we used chronically stressed mice to investigate whether CGRP is involved in depression-like behavior. Each mouse was exposed to restraint and water immersion stress for 15 days. After stress exposure, mice were assessed using behavioral tests: open field test, forced swim test and sucrose preference test. Serum corticosterone levels, hippocampal proliferation and mRNA expression of neurotrophins were measured. After stress exposure, mice exhibited depression-like behavior and decreased CGRP mRNA levels in the hippocampus. Although intracerebroventricular CGRP administration (0.5 nmol) did not alter depression-like behavior after 15-day stress exposure, a single CGRP administration into the brain, before the beginning of the 15-day stress exposure, normalized the behavioral dysfunctions and increased nerve growth factor (Ngf) mRNA levels in stressed mice. Furthermore, in the mouse E14 hippocampal cell line, CGRP treatment induced increased expression of Ngf mRNA. The NGF receptor inhibitor K252a inhibited CGRP's antidepressant-like effects in stressed mice. These results suggest that CGRP expression in the mouse hippocampus is associated with depression-like behavior and changes in Ngf mRNA levels.

No MeSH data available.


Related in: MedlinePlus

Ngf mRNA levels in mouse embryonic E14 hippocampal cell line.CGRP (100 nM) alone or CGRP with a CGRP antagonist, CGRP8-37 (100 nM) incubated for 60 min. CGRP8-37 was added 30 min before the addition of CGRP (saline n = 4, CGRP n = 4, CGRP + CGRP8-37 n = 4). Each bar indicates the mean ± S.E.M.
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f6: Ngf mRNA levels in mouse embryonic E14 hippocampal cell line.CGRP (100 nM) alone or CGRP with a CGRP antagonist, CGRP8-37 (100 nM) incubated for 60 min. CGRP8-37 was added 30 min before the addition of CGRP (saline n = 4, CGRP n = 4, CGRP + CGRP8-37 n = 4). Each bar indicates the mean ± S.E.M.

Mentions: To define the mechanisms underlying the effects of CGRP in the mouse hippocampus, we focused on the expression of various neurotrophic factors, which are known to affect neuronal survival and plasticity of dopaminergic, cholinergic, and serotonergic neurons in the central nervous system18. We first determined whether the expression level of neurotrophic factors was changed by the administration of CGRP i.c.v. before beginning stress exposure (day 1 treatment). As shown in Fig. 5, CGRP pretreatment induced significant increases in Ngf (F(1, 29) = 5.59, P = 0.0250) and c-fos (F(1, 29) = 7.47, P = 0.0106) mRNA expression, but not Bdnf, Cntf, Gdnf, Ntf3 or Ntf5 mRNA expression. To examine whether Ngf expression was sensitive to exogenous CGRP administration, we assessed changes in Ngf mRNA expression levels in the mouse E14 hippocampal cell line. CGRP (100 nM) treatment significantly increased Ngf expression (F(2, 9) = 3.783, P < 0.01, Fig. 6). However, this change was not observed after co-treatment with the CGRF antagonist, CGRP8-37 (100 nM).


Calcitonin gene-related peptide pre-administration acts as a novel antidepressant in stressed mice.

Hashikawa-Hobara N, Ogawa T, Sakamoto Y, Matsuo Y, Ogawa M, Zamami Y, Hashikawa N - Sci Rep (2015)

Ngf mRNA levels in mouse embryonic E14 hippocampal cell line.CGRP (100 nM) alone or CGRP with a CGRP antagonist, CGRP8-37 (100 nM) incubated for 60 min. CGRP8-37 was added 30 min before the addition of CGRP (saline n = 4, CGRP n = 4, CGRP + CGRP8-37 n = 4). Each bar indicates the mean ± S.E.M.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4528222&req=5

f6: Ngf mRNA levels in mouse embryonic E14 hippocampal cell line.CGRP (100 nM) alone or CGRP with a CGRP antagonist, CGRP8-37 (100 nM) incubated for 60 min. CGRP8-37 was added 30 min before the addition of CGRP (saline n = 4, CGRP n = 4, CGRP + CGRP8-37 n = 4). Each bar indicates the mean ± S.E.M.
Mentions: To define the mechanisms underlying the effects of CGRP in the mouse hippocampus, we focused on the expression of various neurotrophic factors, which are known to affect neuronal survival and plasticity of dopaminergic, cholinergic, and serotonergic neurons in the central nervous system18. We first determined whether the expression level of neurotrophic factors was changed by the administration of CGRP i.c.v. before beginning stress exposure (day 1 treatment). As shown in Fig. 5, CGRP pretreatment induced significant increases in Ngf (F(1, 29) = 5.59, P = 0.0250) and c-fos (F(1, 29) = 7.47, P = 0.0106) mRNA expression, but not Bdnf, Cntf, Gdnf, Ntf3 or Ntf5 mRNA expression. To examine whether Ngf expression was sensitive to exogenous CGRP administration, we assessed changes in Ngf mRNA expression levels in the mouse E14 hippocampal cell line. CGRP (100 nM) treatment significantly increased Ngf expression (F(2, 9) = 3.783, P < 0.01, Fig. 6). However, this change was not observed after co-treatment with the CGRF antagonist, CGRP8-37 (100 nM).

Bottom Line: Serum corticosterone levels, hippocampal proliferation and mRNA expression of neurotrophins were measured.Although intracerebroventricular CGRP administration (0.5 nmol) did not alter depression-like behavior after 15-day stress exposure, a single CGRP administration into the brain, before the beginning of the 15-day stress exposure, normalized the behavioral dysfunctions and increased nerve growth factor (Ngf) mRNA levels in stressed mice.These results suggest that CGRP expression in the mouse hippocampus is associated with depression-like behavior and changes in Ngf mRNA levels.

View Article: PubMed Central - PubMed

Affiliation: Department of Life Science, Okayama University of Science, 1-1 Ridai-cho, Kita-ku, Okayama 700-0005, Japan.

ABSTRACT
Calcitonin gene-related peptide (CGRP) is a neuropeptide that has potent vasodilator properties and is involved in various behavioral disorders. The relationship between CGRP and depression-like behavior is unclear. In this study, we used chronically stressed mice to investigate whether CGRP is involved in depression-like behavior. Each mouse was exposed to restraint and water immersion stress for 15 days. After stress exposure, mice were assessed using behavioral tests: open field test, forced swim test and sucrose preference test. Serum corticosterone levels, hippocampal proliferation and mRNA expression of neurotrophins were measured. After stress exposure, mice exhibited depression-like behavior and decreased CGRP mRNA levels in the hippocampus. Although intracerebroventricular CGRP administration (0.5 nmol) did not alter depression-like behavior after 15-day stress exposure, a single CGRP administration into the brain, before the beginning of the 15-day stress exposure, normalized the behavioral dysfunctions and increased nerve growth factor (Ngf) mRNA levels in stressed mice. Furthermore, in the mouse E14 hippocampal cell line, CGRP treatment induced increased expression of Ngf mRNA. The NGF receptor inhibitor K252a inhibited CGRP's antidepressant-like effects in stressed mice. These results suggest that CGRP expression in the mouse hippocampus is associated with depression-like behavior and changes in Ngf mRNA levels.

No MeSH data available.


Related in: MedlinePlus