The role of neuroinflammation, serotonin deficiency and gene expression in the pathology of L-dopa-induced dyskinesia with prolonged Levodopa treatment in a Parkinsonian rat model.
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Date
2023
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Abstract
Parkinson’s disease (PD) is a neurodegenerative disorder, which globally affects 2% of the population
above 65 years old. It is characterized by motor symptoms (bradykinesia, tremor, and rigidity) and nonmotor
symptoms (cognitive deficit, sleeping, and mood disorders). There is no cure for PD, however,
levodopa (L-dopa) therapy is a gold-standard pharmacotherapy for managing motor symptoms. Despite
its effective results, its long-term consumption causes L-dopa-induced dyskinesias (LID). The
pathology of LID is not clear, however growing evidence has indicated that neuroinflammation and
cognitive decline may be significant factors. This study aimed to investigate the role of dysregulated
Nptx2, TH, and FosB genes in the L-dopa-induced cognitive impairment and to assess the role of
serotonin deficiency and neuroinflammation in LID pathology in a Parkinsonian rat model. 72 Male
Sprague-Dawley rats were divided into two equal phases (n=36 per phase), each phase had 3 groups
with n=12 per group. Phase 1 had 3 groups of rats that were injected with L-dopa for 14 days (pre-LID
phase) while phase 2 had rats that were injected with L-dopa for 28 days (LID phase). Animals went
through behavioral assessments and were sacrificed by decapitation to obtain the hippocampus,
prefrontal cortex, and striatum for neurochemical analysis (ELISA and PCR). Overall, results from this
study showed that the continuation of L-dopa triggers a neuroinflammatory response, hence highly
expressing proinflammatory cytokine TNF-α. We found that Nptx2, TH, and FosB genes are
downregulated in the PFC with continued L-dopa therapy. This downregulation was correlated with
LID-induced cognitive decline. Findings from this study suggest that expression of TNF-α and
deficiency of serotonin may play a significant role in the pathology of LID and downregulation of
Nptx2, FosB, and TH genes contribute to LID-induced cognitive decline.
Description
Masters Degree. University of KwaZulu-Natal, Durban.