Changes in Day/Night Activity in the 6-OHDA-Induced Experimental Model of Parkinson's Disease: Exploring Prodromal Biomarkers

• Published in: Frontiers in neuroscience Vol. 14; p. 590029
• Main Authors: Requejo, Catalina, López-de-Ipiña, Karmele, Ruiz-Ortega, José Ángel, Fernández, Elsa, Calvo, Pilar M, Morera-Herreras, Teresa, Miguelez, Cristina, Cardona-Grifoll, Laura, Cepeda, Hodei, Ugedo, Luisa, Lafuente, José Vicente
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 14.10.2020; Frontiers Media S.A
• Subjects: 6-Hydroxydopamine; Amphetamines; Apoptosis; behavior; Biomarkers; Circadian rhythm; Circadian rhythms; Degeneration; Dopamine; Enrichment; home-cage monitoring system; Hydroxylase; Hyperactivity; Immunohistochemistry; Laboratory animals; Mimicry; Movement disorders; Neostriatum; Neurodegenerative diseases; Neuroprotection; Neuroscience; Parkinson's disease; prodromal biomarkers; prodromal Parkinson’s disease symptoms; Rodents; Sleep; Tyrosine 3-monooxygenase; United Kingdom > UK; United States > US; Spain; home-cage monitoring system; 6-hydroxydopamine; rat; prodromal biomarkers; non-motor deficits; prodromal Parkinson’s disease symptoms; behavior; circadian rhythms
• ISSN: 1662-4548; 1662-453X; 1662-453X
• DOI: 10.3389/fnins.2020.590029

The search for experimental models mimicking an early stage of Parkinson's disease (PD) before motor manifestations is fundamental in order to explore early signs and get a better prognosis. Interestingly, our previous studies have indicated that 6-hydroxydopamine (6-OHDA) is a suitable model to induce an early degeneration of the nigrostriatal system without any gross motor impairment. Considering our previous findings, we aim to implement a novel system to monitor rats after intrastriatal injection of 6-OHDA to detect and analyze physiological changes underlying prodromal PD. Twenty male Sprague-Dawley rats were unilaterally injected with 6-OHDA ( = 10) or saline solution ( = 10) into the right striatum and placed in enriched environment cages where the activity was monitored. After 2 weeks, the amphetamine test was performed before the sacrifice. Immunohistochemistry was developed for the morphological evaluation and western blot analysis to assess molecular changes. Home-cage monitoring revealed behavioral changes in response to 6-OHDA administration including significant hyperactivity and hypoactivity during the light and dark phase, respectively, turning out in a change of the circadian timing. A preclinical stage of PD was functionally confirmed with the amphetamine test. Moreover, the loss of tyrosine hydroxylase expression was significantly correlated with the motor results, and 6-OHDA induced early proapoptotic events. Our findings provide evidence for a novel prodromal 6-OHDA model following a customized monitoring system that could give insights to detect non-motor deficits and molecular targets to test neuroprotective/neurorestorative agents.