Nitric Oxide Linked to mGluR5 Upregulates BDNF Synthesis by Activating MMP2 in the Caudate and Putamen after Challenge Exposure to Nicotine in Rats

Nitric oxide (NO) linked to glutamate receptors in the caudate and putamen (CPu) regulates neuroadaptation after drug exposure. Matrix-metalloproteinase (MMP), a Ca2+-dependent zinc-containing endopeptidase, increases mature brain-derived neurotrophic factor (BDNF) synthesis after drug exposure in t...

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Published in:International journal of molecular sciences 2022-09, Vol.23 (18), p.10950
Main Authors: Kim, Jieun, Sohn, Sumin, Kim, Sunghyun, Choe, Eun Sang
Format: Article
Language:English
Subjects:
Brain-derived neurotrophic factor
Calcium
Calcium ions
endopeptidase
Endopeptidases
Exposure
Gelatinase A
glutamate receptor
Glutamic acid receptors (metabotropic)
Inhibitors
Kinases
Matrix metalloproteinase
Matrix metalloproteinases
Metalloproteinase
neurotropic factor
Nicotine
Nitric oxide
Nitric-oxide synthase
Peptides
Putamen
striatum
Xestospongin C
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Summary:Nitric oxide (NO) linked to glutamate receptors in the caudate and putamen (CPu) regulates neuroadaptation after drug exposure. Matrix-metalloproteinase (MMP), a Ca2+-dependent zinc-containing endopeptidase, increases mature brain-derived neurotrophic factor (BDNF) synthesis after drug exposure in the brain. The present study determined that NO synthesis linked to metabotropic glutamate receptor subtype 5 (mGluR5) stimulation after challenge exposure to nicotine activates MMP, which upregulates BDNF synthesis in the CPu. Subcutaneous injection of challenge nicotine (1.0 mg/kg) after repeated injections of nicotine (1.0 mg/kg/day) for 14 days and 7 days of nicotine withdrawal increased MMP2 activity and BDNF expression in the CPu of rats. These increases were prevented by the bilateral intra-CPu infusion of the mGluR5 antagonist, MPEP (0.1 nmol/side), the IP3 receptor antagonist, xestospongin C (0.004 nmol/side) or the neuronal nitric oxide synthase (nNOS) and NO inhibitor, Nω-propyl (0.1 nmol/side) prior to the challenge nicotine. Furthermore, bilateral intra-CPu infusion of the MMP2 inhibitor, OA-Hy (1 nmol/side) prevented the challenge nicotine-induced increase in the expression of BDNF. These findings suggest that elevation of NO synthesis linked to mGluR5 potentiates BDNF synthesis via activation of MMP2 after challenge exposure to nicotine in the CPu of rats.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms231810950