Neuroprotective and anti-inflammatory effects of a therapy combining agonists of nicotinic α7 and σ1 receptors in a rat model of Parkinson's disease
| Autor: | Sylvie Chalon, Jackie Vergote, Sylvain Routier, Frédéric Buron, Claire Tronel, Sophie Serrière, Steven Vetel, Sylvie Bodard, Laura Foucault-Fruchard |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Parkinson's disease Substantia nigra 6-hydroxydopamine Pharmacology lcsh:RC346-429 neuroinflammation 03 medical and health sciences 0302 clinical medicine Developmental Neuroscience medicine microglial activation lcsh:Neurology. Diseases of the nervous system Dopamine transporter Glial fibrillary acidic protein biology Tyrosine hydroxylase PHA 543613 business.industry Dopaminergic Neurodegeneration astrocytes neurodegeneration PRE-084 medicine.disease 030104 developmental biology Nicotinic agonist nicotinic a7 receptor parkinson's disease pha 543613 pre-084 sigma-1 receptor nervous system nicotinic α7 receptor biology.protein business 030217 neurology & neurosurgery Research Article |
| Zdroj: | Neural Regeneration Research Neural Regeneration Research, Vol 16, Iss 6, Pp 1099-1104 (2021) |
| ISSN: | 1673-5374 |
| Popis: | To date there is no treatment able to stop or slow down the loss of dopaminergic neurons that characterizes Parkinson's disease. It was recently observed in a rodent model of Alzheimer's disease that the interaction between the a7 subtype of nicotinic acetylcholine receptor (a7-nAChR) and sigma-1 receptor (s1-R) could exert neuroprotective effects through the modulation of neuroinflammation which is one of the key components of the pathophysiology of Parkinson's disease. In this context, the aim of the present study was to assess the effects of the concomitant administration of N-(3R)-1-azabicyclo[2.2.2]oct-3-yl-furo[2,3-c]pyridine-5-carboxamide (PHA) 543613 as an a7-nAChR agonist and 2-(4-morpholinethyl) 1-phenylcyclohexanecarboxylate (PRE)-084 as a s1-R agonist in a well-characterized 6-hydroxydopamine rat model of Parkinson's disease. The animals received either vehicle separately or the dual therapy PHA/PRE once a day until day 14 post-lesion. Although no effect was noticed in the amphetamine-induced rotation test, our data has shown that the PHA/PRE treatment induced partial protection of the dopaminergic neurons (15–20%), assessed by the dopamine transporter density in the striatum and immunoreactive tyrosine hydroxylase in the substantia nigra. Furthermore, this dual therapy reduced the degree of glial activation consecutive to the 6-hydroxydopamine lesion, i.e, the 18 kDa translocation protein density and glial fibrillary acidic protein staining in the striatum, and the CD11b and glial fibrillary acidic protein staining in the substantia nigra. Hence, this study reports for the first time that concomitant activation of a7-nAChR and s1-R can provide a partial recovery of the nigro-striatal dopaminergic neurons through the modulation of microglial activation. The study was approved by the Regional Ethics Committee (CEEA Val de Loire n°19) validated this protocol (Authorization N°00434.02) on May 15, 2014. |
| Databáze: | OpenAIRE |
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