Neurodegeneration, Neuroprotection, and Disease-Oriented NeuroscienceResearch PaperTime-course of nigrostriatal neurodegeneration and neuroinflammation in the 6-hydroxydopamine-induced axonal and terminal lesion models of Parkinson's disease in the rat
Research Highlights
▶Spatiotemporal pattern of neuroinflammation differs in the 6-hydroxydopamine-induced axonal and terminal lesion models of Parkinson's disease. ▶The terminal lesion is associated with rapid striatal microglial activation and dopaminergic deafferentation. ▶In both lesion models, activation of glial cells precedes or coincides with 6-hydroxydopamine-induced nigrostriatal degeneration.
Section snippets
Animals
Male Sprague–Dawley rats (Charles River, UK) were used in this study (n=82), weighing 225–250 g at the start of the experiment. They were housed under a 12 h light:dark cycle in a room maintained at 21±2 °C and had access to food and water ad libitum. All procedures were carried out under licence from the Irish Department of Health and Children, were approved by the Animal Care and Research Ethics Committee of the National University of Ireland, Galway and were in compliance with the European
Time-course of neurodegeneration following terminal and axonal lesion
Quantitative TH immunostaining was used to determine the time-course of nigrostriatal neurodegeneration induced by injection of 6-hydroxydopamine or vehicle into the nigrostriatal terminals or axons.
Discussion
This study sought to establish the temporal relationship between nigrostriatal neurodegeneration and neuroinflammation in the two most commonly used rat models of Parkinson's disease—those induced by terminal or axonal administration of the catecholaminergic neurotoxin 6-hydroxydopamine. Although a number of other studies have investigated the neuroinflammatory response in terminal and axonal 6-hydroxydopamine lesion models, to our knowledge, none have directly compared the time-course of
Acknowledgments
S. Walsh is a recipient of an EMBARK PhD studentship from the Irish Research Council for Science, Engineering and Technology.
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2021, Brain ResearchCitation Excerpt :The decreases in SN TH and in striatal dopamine take place with minor changes in the body weight or in gross motor behavior of OXY-SAP-treated rats compared to BLANK-SAP-or PBS-treated rats. This is in line with studies showing that a 50–60 % reduction of striatal dopamine rarely induces dramatic changes in body weight or gross behavior of rodents (see Bharatiya et al., 2020; Ungerstedt et al., 1974; Lee et al., 1996; Deumens et al., 2002; Ferro et al., 2005; Walsh et al., 2011; Su et al., 2018). However, such reduction causes differences in locomotor activity in the open field or motor coordination in the rotarod test in rats, or in turning behavior induced by dopaminergic drugs in rats with unilateral nigrostriatal lesions (Bharatiya et al., 2020; Fornaguera et al., 1993; Ungerstedt, 1971; Sindhu et al., 2006).