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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

Experimental timelines.Protocol 1: to observe spontaneous behavior and depression-related behavior, open field test (OF) and forced swim test (FST) performances were assessed on the day following the 15-day stress exposure (day 16). Protocol 2: to observe depression-related behavior, the sucrose preference test was assessed days 1–3 after the 15-day stress exposure (day 16–18). Protocol 3: to observe serum corticosterone and mRNA levels of neurotrophic factors, blood and brain samples were collected at the end of the 15-day stress exposure from mice that had not undergone behavioral testing. Protocol 4: to study cell proliferation in the hippocampus, a single injection of 5-bromo-2-deoxyuridine (BrdU; 50 mg/kg, i.p.), was administered 3 times on day 15 of the 15-day stress exposure.
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f8: Experimental timelines.Protocol 1: to observe spontaneous behavior and depression-related behavior, open field test (OF) and forced swim test (FST) performances were assessed on the day following the 15-day stress exposure (day 16). Protocol 2: to observe depression-related behavior, the sucrose preference test was assessed days 1–3 after the 15-day stress exposure (day 16–18). Protocol 3: to observe serum corticosterone and mRNA levels of neurotrophic factors, blood and brain samples were collected at the end of the 15-day stress exposure from mice that had not undergone behavioral testing. Protocol 4: to study cell proliferation in the hippocampus, a single injection of 5-bromo-2-deoxyuridine (BrdU; 50 mg/kg, i.p.), was administered 3 times on day 15 of the 15-day stress exposure.

Mentions: Animals (8 weeks old) in the stress groups were subjected to 3 h restraint for 15 days starting at 10:00 AM daily, using a protocol modified from a previously reported chronic stress model38. Each mouse was placed in a modified 50 mL polyethylene tube fitted with multiple air holes and immersed in a constant temperature water bath (28 °C) using a tube stand. In the morning and afternoon of day 16, after 15 days’ exposure to stress, we carried out open field and forced swim tests. The sucrose preference test was administered for 3 days following the 15-day stress exposure. To determine whether the 15-day stress exposure resulted in changes in serum corticosterone levels and the mRNA expression level of neurotrophic factors, blood and brain samples were collected in subjects that did not undergo behavioral testing. Furthermore, to evaluate hippocampal proliferation, brain samples were also collected from mice that did not undergo behavioral testing (Fig. 8).


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)

Experimental timelines.Protocol 1: to observe spontaneous behavior and depression-related behavior, open field test (OF) and forced swim test (FST) performances were assessed on the day following the 15-day stress exposure (day 16). Protocol 2: to observe depression-related behavior, the sucrose preference test was assessed days 1–3 after the 15-day stress exposure (day 16–18). Protocol 3: to observe serum corticosterone and mRNA levels of neurotrophic factors, blood and brain samples were collected at the end of the 15-day stress exposure from mice that had not undergone behavioral testing. Protocol 4: to study cell proliferation in the hippocampus, a single injection of 5-bromo-2-deoxyuridine (BrdU; 50 mg/kg, i.p.), was administered 3 times on day 15 of the 15-day stress exposure.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f8: Experimental timelines.Protocol 1: to observe spontaneous behavior and depression-related behavior, open field test (OF) and forced swim test (FST) performances were assessed on the day following the 15-day stress exposure (day 16). Protocol 2: to observe depression-related behavior, the sucrose preference test was assessed days 1–3 after the 15-day stress exposure (day 16–18). Protocol 3: to observe serum corticosterone and mRNA levels of neurotrophic factors, blood and brain samples were collected at the end of the 15-day stress exposure from mice that had not undergone behavioral testing. Protocol 4: to study cell proliferation in the hippocampus, a single injection of 5-bromo-2-deoxyuridine (BrdU; 50 mg/kg, i.p.), was administered 3 times on day 15 of the 15-day stress exposure.
Mentions: Animals (8 weeks old) in the stress groups were subjected to 3 h restraint for 15 days starting at 10:00 AM daily, using a protocol modified from a previously reported chronic stress model38. Each mouse was placed in a modified 50 mL polyethylene tube fitted with multiple air holes and immersed in a constant temperature water bath (28 °C) using a tube stand. In the morning and afternoon of day 16, after 15 days’ exposure to stress, we carried out open field and forced swim tests. The sucrose preference test was administered for 3 days following the 15-day stress exposure. To determine whether the 15-day stress exposure resulted in changes in serum corticosterone levels and the mRNA expression level of neurotrophic factors, blood and brain samples were collected in subjects that did not undergo behavioral testing. Furthermore, to evaluate hippocampal proliferation, brain samples were also collected from mice that did not undergo behavioral testing (Fig. 8).

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