Abstract
Background: Parkinson’s disease (PD) is described as an age-related neurodegenerative disorder. However, the vast majority of research is carried out using experimental models of young animals lacking the implications of the decline processes associated with aging. It has been suggested that several molecular pathways are involved in the perpetuation of the degeneration and the neuroinflammation in PD. Among others, mitogen-activated protein kinases (MAPKs) have been highly implicated in the development of PD, and regulating components of their activity are indicated as promising therapeutic targets.Methods: To further define how MAPKs expression is related to the glial response and neuronal cell death, Parkinsonism was induced under an acute regimen in old mice. Moreover, the sacrifice was carried out at different time points (4, 8, 24, and 48 h) after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) injections to describe the early dynamic changes over time produced by the intoxication.Results: The results revealed that neuronal death increases as glial response increases in the nigrostriatal pathway. It was observed that both processes increase from 4 h in the ventral mesencephalon (VM), and neuronal death becomes significant at 48 h. In the striatum, they were significantly increased from 48 h after the MPTP administration compared with that in the control mice. Moreover, the p-ERK levels decrease, while phospho-p38 expression increases specifically in the striatum at 48 h after MPTP intoxication.Conclusions: The importance of these data lies in the possibility of elucidating the underlying mechanisms of neurodegenerative processes under aging conditions to provide knowledge for the search of solutions that slow down the progression of PD.
Highlights
Parkinson’s disease (PD) is the second most common neurodegenerative disorder in the world, affecting 100–200 per 100,000 people over 65 years old (Tysnes and Storstein, 2017)
Several studies suggest that the complex interactions between the deleterious mechanisms of aging involved levels of chronic mild inflammation in the substantia nigra pars compacta (SNpc), producing those dopaminergic neurons that become more vulnerable to degeneration (Calabrese et al, 2018)
Parkinsonism was induced by intraperitoneal injections of MPTP (Sigma–Aldrich; 30 mg/kg/dose, two doses, 2-h interval) dissolved in saline (Annese et al, 2015)
Summary
Parkinson’s disease (PD) is the second most common neurodegenerative disorder in the world, affecting 100–200 per 100,000 people over 65 years old (Tysnes and Storstein, 2017). Its main pathological feature is the chronic and progressive loss of dopaminergic neurons within the substantia nigra pars compacta (SNpc). This leads towards a decrease in dopamine levels in the nigrostriatal pathway (Kastner et al, 1994) and in addition, to proteinaceous inclusions known as Lewy bodies (Cuenca et al, 2019). Several studies suggest that the complex interactions between the deleterious mechanisms of aging involved levels of chronic mild inflammation in the SNpc, producing those dopaminergic neurons that become more vulnerable to degeneration (Calabrese et al, 2018). Parkinson’s disease (PD) is described as an age-related neurodegenerative disorder. Mitogen-activated protein kinases (MAPKs) have been highly implicated in the development of PD, and regulating components of their activity are indicated as promising therapeutic targets
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