Occurrence of neuronal inclusions combined with increased nigral expression of α-synuclein within dopaminergic neurons following treatment with amphetamine derivatives in mice

Revisiting oxidative stress and mitochondrial dysfunction in the pathogenesis of Parkinson disease—resemblance to the effect of amphetamine drugs of abuse

“…In particular, amphetamines were previously described to induce neuronal inclusions and affect proteins belonging to the UPS, in the central nervous system [298]; moreover,ultrastructural and molecular changes were similar to those occurring in PD [299]. AmphetamineͲinduced neuronal inclusions present many features similar to those observed in PD, and the maturation of these inclusions can be reproduced by continuous exposure to parkinsonian neurotoxins such as rotenone [84,300]or MPTP [301].In mice, occurrence of neuronal inclusions combined with increased nigral expression of alphaͲsyn within dopaminergic neurons were found upon treatment with amphetamine derivatives [302], similarly to what occurs following administration of the parkinsonian toxin MPTP [303]. Furthermore, treatment of mice with methamphetamine increased markers of oxidative stress in the striatum and increased the levels of oligomeric alphaͲsyn in the SN [304].…”

Epigenetic upregulation of alpha-synuclein in the rats exposed to methamphetamine

“…A number of evidences demonstrated that aggregation of exogenous α-synuclein exhibited potent neurotoxicity to induce remarkable neuroinflammation and the neuronal apoptotic cell death in the brain (Luk et al, 2012). Previous studies reported that multiple injections with METH significantly increased the expression of α-synuclein in the substantial nigra, which was primarily located in the dopaminergic (tyrosine hydroxylase -immunopositive) neurons in the rodents (Fornai et al, 2005;Jung et al, 2010). Knockdown the expression of α-synuclein substantially recovered the cell viability and reduced the production of reactive oxygen species in the cultured dopaminergic-like neuroblastoma SH-SY5Y cells treated with METH .…”

“…Meanwhile, increase of α-synuclein is substantially associated with the central neuroinflammation and neurodegeneration in the substantia nigra in the rodent model of PD (Lee et al, 2014). It was previously reported that repeated exposure to METH increased the expression of α-synuclein in the dopaminergic neurons in the substantia nigra in the rodent (Fornai et al, 2005;Mauceli et al, 2006), while the mechanism remained unclear. Currently, emerging evidences implied critical involvement of epigenetic modification of the expression of specific genes, including Snca, in the pathogenesis and development of several neurodegenerative diseases (Desplats et al, 2011;Tan et al, 2014).…”

Reprint of: Revisiting oxidative stress and mitochondrial dysfunction in the pathogenesis of Parkinson disease—resemblance to the effect of amphetamine drugs of abuse

“…Amphetamine-induced neuronal inclusions present many features similar to those observed in PD, and the maturation of these inclusions can be reproduced by continuous exposure to parkinsonian neurotoxins such as rotenone [84,301] or MPTP [302]. In mice, the occurrence of neuronal inclusions combined with increased nigral expression of a-syn within dopaminergic neurons was found upon treatment with amphetamine derivatives [303], similar to what occurs after administration of the parkinsonian toxin MPTP [304]. Furthermore, treatment of mice with methamphetamine increased markers of oxidative stress in the striatum and increased the levels of oligomeric a-syn in the SN [305].…”