title: Alterations of gene expression of sodium channels in dorsal root ganglion neurons of estrogen receptor knockout (ERKO) mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
abstract: Estrogen receptors (ERα and ERβ) mediate the neuroprotection of estrogens against MPTP-induced striatal dopamine (DA) depletion. Pain is an important and distressing symptom in Parkinson's disease (PD). Voltage-gated sodium channels in sensory neurons are involved in the development of neuropathic pain. In this study, MPTP caused changes in nociception and alterations of gene expression of voltage-gated sodium channels in dorsal root ganglion (DRG) neurons in ER knockout (ERKO) mice were investigated. We found that administration of MPTP (11 mg/kg) to WT mice led to an extensive depletion of DA and its two metabolites, αERKO mice were observed to be more susceptible to MPTP toxicity than βERKO or WT mice. In addition, we found that the mRNA levels of TTX-S and TTX-R sodium channel subtypes were differentially affected in MPTP-treated WT animals. The MPTP-induced up-regulation of Nav1.1 and Nav1.9, down-regulation of Nav1.6 in DRG neurons may be through ERβ, up-regulation of Nav1.7 and down-regulation of Nav1.8 are dependent on both ERα and ERβ. Therefore, the MPTP-induced alterations of gene expression of sodium channels in DRG neurons could be an important mechanism to affect excitability and nociceptive thresholds, and the ERs appear to play a role in nociception in PD.
authors.affiliation: Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Ding
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Jingli
authors.initials: J
authors.lastname: Liu
authors.forename: Wenyi
authors.initials: W
authors.lastname: Qian
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Rong
authors.initials: R
authors.lastname: Gao
authors.forename: Hang
authors.initials: H
authors.lastname: Xiao
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D001679:Biogenic Amines / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010147:Pain Measurement; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D061566:Voltage-Gated Sodium Channels / Q000235:genetics* / Q000378:metabolism
chemical_list: D001679:Biogenic Amines; D015259:Dopamine Agents; D011960:Receptors, Estrogen; D061566:Voltage-Gated Sodium Channels; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine