title: Selective A2Areceptors blockade reduces degeneration of substantia nigra dopamine neurons in a rotenone-induced rat model of Parkinson's disease: A histological study.
abstract: Parkinson's disease (PD) is characterized by a loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Adenosine is a neuromodulator that inhibit the release of dopamine via a disinhibitory mechanism. In this study, we investigated the neuroprotective effect of 8-cyclopentyl-1,3-dipropylxanthine and ZM241385 (respectively, A1and A2Areceptors antagonists), on nigrostriatal dopamine neurons degradation reduction in a rotenone-induced PD model using histopathological and immunohistochemical methods. 32 male rats were randomly divided into 4 groups, 8 in each one: vehicle control (1ml/kg/48h), rotenone (1.5mg/kg/48h,s.c.), ZM241385 (3.3mg/kg/day, i.p) and 8-cyclopentyl-1,3-dipropylxanthine (5mg/kg/day, i.p). 24h after the last rotenone injection, animals were sacrificed and their brains were sectioned and prepared for histopathological staining with hematoxylin and eosin, cresyl violet for Nissl-staining, Mallory's phosphotungestic acid haematoxylin staining as well as for immunohistochemical staining for tyrosine hydroxylase. Our study showed that A2A-receptor blockade by ZM241385, but not A1receptor blocking by 8-cyclopentyl-1,3-dipropylxanthine, decreased histopathological degeneration in SNpc neurons and hindered the reduction in dopamine levels caused by rotenone application. These results indicate that the selective A2A, but not A1 receptor blocking, has a neuroprotective effect, and may provide a more selective pharmacological strategy for the treatment of PD symptoms.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt. Electronic address: afathalla_pgs@med.suez.edu.eg.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Fathalla
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
authors.forename: Amira M
authors.initials: AM
authors.lastname: Soliman
authors.affiliation: Department of Veterans Affairs, New Jersey Health Care System, East Orange, NJ, USA; School of Social Sciences and Psychology and Marcs Institute for Brain and Behaviour, Western Sydney University, Sydney, New South Wales, Australia. Electronic address: a.moustafa@westernsydney.edu.au.
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Moustafa
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000378:metabolism; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D010300:Parkinson Disease / Q000378:metabolism*; D051381:Rats; D043705:Receptor, Adenosine A2A / Q000187:drug effects* / Q000378:metabolism; D012402:Rotenone / Q000494:pharmacology; D013378:Substantia Nigra / Q000187:drug effects* / Q000473:pathology*
chemical_list: D018696:Neuroprotective Agents; D043705:Receptor, Adenosine A2A; D012402:Rotenone; D004298:Dopamine
keywords: Adenosine; Dopamine; Histological stain; Immunohistochemical stain; Parkinson’s disease; Rotenone