The effects of physical exercise on nonmotor symptoms and on neuroimmune RAGE network in experimental parkinsonism

• Type: Article in International Scientific Journal
• Date: 2017

Authors

Viana, SD (Author) Other; Pita, IR (Author) Other; Lemos, C (Author) Other; Rial, D (Author) Other; Couceiro, P (Author) Other; Rodrigues Santos, P (Author) Other; Caramelo, F (Author) Other; Felix Carvalho (Author) FFUP; Ali, SF (Author) Other; Prediger, RD (Author) Other; Fontes Ribeiro, CAF (Author) Other; Pereira, FC (Author) Other

Journal

Title: Journal of Applied Physiology

Vol. 123

Pages: 161-171

ISSN: 8750-7587

Publisher: American Physiological Society

Indexing

ISI Web of Knowledge - 1 Citation

Scopus - 5 Citations

Other information

Authenticus ID: P-00N-0GP

DOI: 10.1152/japplphysiol.01120.2016

Abstract (EN): Parkinson's disease (PD) prodromal stages comprise neuropsychiatric perturbations that critically compromise a patient's quality of life. These nonmotor symptoms (NMS) are associated with exacerbated innate immunity, a hallmark of overt PD. Physical exercise (PE) has the potential to improve neuropsychiatric deficits and to modulate immune network including receptor for advanced glycation end products (RAGE) and Toll-like receptors (TLRs) in distinct pathological settings. Accordingly, the present study aimed to test the hypothesis that PE 1) alleviates PD NMS and 2) modulates neuroimmune RAGE network in experimental PD. Adult Wistar rats subjected to long-term mild treadmill were administered intranasally with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and probed for PD NMS before the onset of motor abnormalities. Twelve days after MPTP, neuroimmune RAGE network transcriptomics (real-time quantitative PCR) was analyzed in frontal cortex, hippocampus, and striatum. Untrained MPTP animals displayed habit-learning and motivational deficits without gross motor impairments (cued version of watermaze, splash, and open-field tests, respectively). A suppression of RAGE and neuroimmune-related genes was observed in frontal cortex on chemical and physical stressors (untrained MPTP: RAGE, TLR5 and -7, and p22 NADPH oxidase; saline-trained animals: RAGE, TLR1 and -5 to -11, TNF-alpha, IL-1 beta, and p22 NADPH oxidase), suggesting the recruitment of compensatory mechanisms to restrain innate inflammation. Notably, trained MPTP animals displayed nor-mal cognitive/motivational performances. Additionally, these animals showed normal RAGE expression and neuroprotective PD-related DJ-1 gene upregulation in frontal cortex when compared with untrained MPTP animals. These findings corroborate PE efficacy in improving PD NMS and newly identify RAGE network as a neural substrate for exercise intervention. Additional research is warranted to unveil functional consequences of PE-induced modulation of RAGE/DJ-1 transcriptomics in PD premotor stages.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11