title: Cholinergic and Dopaminergic Alterations in Nigrostriatal Neurons Are Involved in Environmental Enrichment Motor Protection in a Mouse Model of Parkinson's Disease.
abstract: Parkinson's disease (PD) is the second most common neurodegenerative disease in the world, being characterized by dopaminergic neurodegeneration of substantia nigra pars compacta. PD pharmacotherapy has been based on dopamine replacement in the striatum with the dopaminergic precursor 3,4-dihydroxyphenylalanine (L-DOPA) and/or with dopaminergic agonists, alongside anticholinergic drugs in order to mitigate the motor abnormalities. However, these practices neither prevent nor stop the progression of the disease. Environmental enrichment (EE) has effectively prevented several neurodegenerative processes, mainly in preclinical trials. Several studies have demonstrated that EE induces biological changes, bearing on cognitive enhancement, neuroprotection, and on the attenuation of the effects of stress, anxiety, and depression. Herein, we investigated whether EE could prevent the motor, biochemical, and molecular abnormalities in a murine model of PD induced by 1-methyl-4-phenyl-2,3-dihydropyridine (MPTP). Our results show that EE does not prevent the dopaminergic striatal depletion induced by MPTP, despite having averted the MPTP-induced hyperlocomotion. However, it was able to slow down and avoid, respectively, the 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) depletion. Analysis of dopaminergic mRNA alterations in the midbrain showed that D1R expression was increased by MPTP, while the normal expression level of this receptor was restored by EE. As for the cholinergic system, MPTP led to a decrease in the ChAT gene expression while increasing the expression of both AChE and M1R. EE attenuated and prevented-respectively-ChAT and M1R gene expression alterations triggered by MPTP in the midbrain. Overall, our data brings new evidence supporting the neuroprotective potential of EE in PD, focusing on the interaction between dopaminergic and cholinergic systems.
authors.affiliation: Department of Physiological Sciences, Health Sciences Center, Federal University of Espirito Santo, Vitoria, ES, 29043-910, Brazil.|Laboratory of Molecular and Behavioral Neurobiology, Health Sciences Center, Federal University of Espirito Santo, Vitoria, ES, 29.043-910, Brazil.
authors.forename: Willyan Franco
authors.initials: WF
authors.lastname: Hilario
authors.affiliation: Department of Physiological Sciences, Health Sciences Center, Federal University of Espirito Santo, Vitoria, ES, 29043-910, Brazil.|Laboratory of Molecular and Behavioral Neurobiology, Health Sciences Center, Federal University of Espirito Santo, Vitoria, ES, 29.043-910, Brazil.
authors.forename: Alice Laschuk
authors.initials: AL
authors.lastname: Herlinger
authors.affiliation: Department of Physiological Sciences, Health Sciences Center, Federal University of Espirito Santo, Vitoria, ES, 29043-910, Brazil.|Laboratory of Molecular and Behavioral Neurobiology, Health Sciences Center, Federal University of Espirito Santo, Vitoria, ES, 29.043-910, Brazil.|Graduate Program in Neuroscience, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, 31.270-901, Brazil.
authors.forename: Lorena Bianchine
authors.initials: LB
authors.lastname: Areal
authors.affiliation: Department of Physiological Sciences, Health Sciences Center, Federal University of Espirito Santo, Vitoria, ES, 29043-910, Brazil.|Laboratory of Molecular and Behavioral Neurobiology, Health Sciences Center, Federal University of Espirito Santo, Vitoria, ES, 29.043-910, Brazil.
authors.forename: Lívia Silveira
authors.initials: LS
authors.lastname: de Moraes
authors.affiliation: Department of Physiological Sciences, Health Sciences Center, Federal University of Espirito Santo, Vitoria, ES, 29043-910, Brazil.|Laboratory of Molecular and Behavioral Neurobiology, Health Sciences Center, Federal University of Espirito Santo, Vitoria, ES, 29.043-910, Brazil.
authors.forename: Tamara Andrea Alarcon
authors.initials: TA
authors.lastname: Ferreira
authors.affiliation: Department of Physiological Sciences, Health Sciences Center, Federal University of Espirito Santo, Vitoria, ES, 29043-910, Brazil.|Laboratory of Molecular and Behavioral Neurobiology, Health Sciences Center, Federal University of Espirito Santo, Vitoria, ES, 29.043-910, Brazil.
authors.forename: Tassiane Emanuelle Servane
authors.initials: TE
authors.lastname: Andrade
authors.affiliation: Department of Physiological Sciences, Health Sciences Center, Federal University of Espirito Santo, Vitoria, ES, 29043-910, Brazil.|Laboratory of Molecular and Behavioral Neurobiology, Health Sciences Center, Federal University of Espirito Santo, Vitoria, ES, 29.043-910, Brazil.
authors.forename: Cristina
authors.initials: C
authors.lastname: Martins-Silva
authors.affiliation: Department of Physiological Sciences, Health Sciences Center, Federal University of Espirito Santo, Vitoria, ES, 29043-910, Brazil. rita.pires@ufes.br.|Laboratory of Molecular and Behavioral Neurobiology, Health Sciences Center, Federal University of Espirito Santo, Vitoria, ES, 29.043-910, Brazil. rita.pires@ufes.br.|Graduate Program in Neuroscience, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, 31.270-901, Brazil. rita.pires@ufes.br.
authors.forename: Rita Gomes Wanderley
authors.initials: RG
authors.lastname: Pires
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D006719:Homovanillic Acid / Q000378:metabolism; D008124:Locomotion; D020267:MPTP Poisoning / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D011950:Receptors, Cholinergic / Q000235:genetics / Q000378:metabolism; D011954:Receptors, Dopamine / Q000235:genetics / Q000378:metabolism; D012919:Social Behavior; D013378:Substantia Nigra / Q000166:cytology / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D011950:Receptors, Cholinergic; D011954:Receptors, Dopamine; D015102:3,4-Dihydroxyphenylacetic Acid; D000109:Acetylcholine; D004298:Dopamine; D006719:Homovanillic Acid
keywords: Cholinergic system; Dopaminergic system; Enriched environment; MPTP; Neuroprotection; Parkinson’s disease