Estrogen receptors modulate striatal metabotropic receptor type 5 in intact and MPTP male mice model of Parkinson's disease.
Identifieur interne : 000361 ( Main/Exploration ); précédent : 000360; suivant : 000362Estrogen receptors modulate striatal metabotropic receptor type 5 in intact and MPTP male mice model of Parkinson's disease.
Auteurs : S. Al-Sweidi [Canada] ; M. Morissette [Canada] ; T. Di Paolo [Canada]Source :
- The Journal of steroid biochemistry and molecular biology [ 1879-1220 ] ; 2016.
Abstract
Glutamate is the most important brain excitatory neurotransmitter and glutamate overactivity is well documented in Parkinson's disease (PD). Metabotropic glutamate (mGlu) receptors are reported to interact with membrane estrogen receptors (ERs) and more specifically the mGlu5 receptor subtype. 17β-estradiol and mGlu5 antagonists have neuroprotective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. We previously reported that ERα and ERβ are involved in neuroprotection following MPTP toxicity. The present study investigated the implication of ERs on the mGlu5 receptor adaptive response to MPTP toxicity in the brain of wild type (WT), ER knockout (ERKO)α and ERKOβ male mice. Autoradiography of [(3)H]ABP688 specific binding to striatal mGlu5 receptors showed a dorsal/ventral gradient similar for WT, ERKOα and ERKOβ mice with higher values ventrally. The lateral septum had highest [(3)H]ABP688 specific binding that remained unchanged in all experimental groups. ERKOα and ERKOβ mice had similarly lower striatal [(3)H]ABP688 specific binding than WT mice as measured also by Western blots. MPTP dose-dependently decreased striatal [(3)H]ABP688 specific binding in WT but not in ERKOα and ERKOβ mice; this correlated positively with striatal dopamine concentrations. A 17β-estradiol treatment for 10 days left unchanged striatal [(3)H]ABP688 specific binding of unlesioned mice of the three genotypes. 17β-estradiol treatment for 5 days before MPTP and for 5 days after partially prevented the mGlu5 receptor decrease only in WT MPTP mice and this was associated with higher BDNF striatal contents. These results thus show that in male mice ERs affect striatal mGlu5 receptor levels and their response to MPTP.
DOI: 10.1016/j.jsbmb.2016.02.004
PubMed: 26873133
Affiliations:
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Morissette</name><affiliation wicri:level="1"><nlm:affiliation>Neuroscience Research Unit, Centre Hospitalier Universitaire de Québec, CHUL, Quebec City, Quebec G1V 4G2, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Neuroscience Research Unit, Centre Hospitalier Universitaire de Québec, CHUL, Quebec City, Quebec G1V 4G2</wicri:regionArea><wicri:noRegion>Quebec G1V 4G2</wicri:noRegion></affiliation></author><author><name sortKey="Di Paolo, T" sort="Di Paolo, T" uniqKey="Di Paolo T" first="T" last="Di Paolo">T. Di Paolo</name><affiliation wicri:level="1"><nlm:affiliation>Neuroscience Research Unit, Centre Hospitalier Universitaire de Québec, CHUL, Quebec City, Quebec G1V 4G2, Canada; Faculty of Pharmacy, Laval University, Quebec City, Quebec G1K 7P4, Canada. Electronic address: therese.dipaolo@crchul.ulaval.ca.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Neuroscience Research Unit, Centre Hospitalier Universitaire de Québec, CHUL, Quebec City, Quebec G1V 4G2, Canada; Faculty of Pharmacy, Laval University, Quebec City, Quebec G1K 7P4</wicri:regionArea><wicri:noRegion>Quebec G1K 7P4</wicri:noRegion></affiliation></author></analytic><series><title level="j">The Journal of steroid biochemistry and molecular biology</title><idno type="eISSN">1879-1220</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Glutamate is the most important brain excitatory neurotransmitter and glutamate overactivity is well documented in Parkinson's disease (PD). Metabotropic glutamate (mGlu) receptors are reported to interact with membrane estrogen receptors (ERs) and more specifically the mGlu5 receptor subtype. 17β-estradiol and mGlu5 antagonists have neuroprotective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. We previously reported that ERα and ERβ are involved in neuroprotection following MPTP toxicity. The present study investigated the implication of ERs on the mGlu5 receptor adaptive response to MPTP toxicity in the brain of wild type (WT), ER knockout (ERKO)α and ERKOβ male mice. Autoradiography of [(3)H]ABP688 specific binding to striatal mGlu5 receptors showed a dorsal/ventral gradient similar for WT, ERKOα and ERKOβ mice with higher values ventrally. The lateral septum had highest [(3)H]ABP688 specific binding that remained unchanged in all experimental groups. ERKOα and ERKOβ mice had similarly lower striatal [(3)H]ABP688 specific binding than WT mice as measured also by Western blots. MPTP dose-dependently decreased striatal [(3)H]ABP688 specific binding in WT but not in ERKOα and ERKOβ mice; this correlated positively with striatal dopamine concentrations. A 17β-estradiol treatment for 10 days left unchanged striatal [(3)H]ABP688 specific binding of unlesioned mice of the three genotypes. 17β-estradiol treatment for 5 days before MPTP and for 5 days after partially prevented the mGlu5 receptor decrease only in WT MPTP mice and this was associated with higher BDNF striatal contents. These results thus show that in male mice ERs affect striatal mGlu5 receptor levels and their response to MPTP.</div></front></TEI><affiliations><list><country><li>Canada</li></country></list><tree><country name="Canada"><noRegion><name sortKey="Al Sweidi, S" sort="Al Sweidi, S" uniqKey="Al Sweidi S" first="S" last="Al-Sweidi">S. Al-Sweidi</name></noRegion><name sortKey="Di Paolo, T" sort="Di Paolo, T" uniqKey="Di Paolo T" first="T" last="Di Paolo">T. 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