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Neuroprotective and anti-inflammatory effects of a therapy combining agonists of nicotinic α7 and σ1 receptors in a rat model of Parkinson's disease
- Source :
- Neural Regeneration Research, Neural Regeneration Research, Vol 16, Iss 6, Pp 1099-1104 (2021)
- Publication Year :
- 2020
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 16735374
- Volume :
- 16
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Neural regeneration research
- Accession number :
- edsair.doi.dedup.....134484deee9e764e5e615f9c11d06c37