Differences between subacute and chronic MPTP mice models: investigation of dopaminergic neuronal degeneration and α‐synuclein inclusions

Abstract

Animal models are invaluable tools to study neurodegenerative disorders but a general consensus on the most accurate rodent model of Parkinson's disease has not been reached. Here, we examined how different methods of MPTP administration influence the degeneration of the dopaminergic (DA) system. Adult male C57BL/6 mice were treated with the same cumulative dose of MPTP following four distinct procedures: (i) subacute i.p. injections; (ii) 28-day chronic s.c. infusion; (iii) 28-day chronic i.p. infusion; and (iv) 14-day chronic i.p. infusion. Subacute MPTP treatment significantly affected all aspects of the DA system within the nigral and striatal territories. In contrast, the 28-day chronic s.c. infusion did not significantly alter any components of the DA system. The 28-and 14-day chronic i.p. infusions induced loss of tyrosine hydroxylase (TH)-positive cells correlated with a decrease in Nurr1 mRNA levels, but no significant decrease in the density of TH striatal fibers. Importantly, however, only the 14-day chronic MPTP i.p. infusion protocol promoted the formation of neuronal inclusions as noted by the expression of a-synuclein protein within the cytoplasm of TH nigral neurons. Overall, we found that the 14-day chronic MPTP i.p. infusion reproduces more accurately the pathological characteristics of early stage Parkinson's disease.

Transgenic conversion of omega-6 into omega-3 fatty acids in a mouse model of Parkinson's disease

“…The MPTP treatment was performed at 6 months of age and consisted of 7 ip injections of a MPTP•HCl solution (20 mg free base/kg) (Sigma, St. Louis, MO), freshly dissolved in 0.9% saline. MPTP was administered twice on the fi rst 2 days of the experimental protocol at 12 h intervals, and once a day on the 3 following days, as previously described ( 4,21 ). Remaining animals received 0.9% saline ip following the regime used for MPTP.…”

“…Remaining animals received 0.9% saline ip following the regime used for MPTP. This particular MPTP procedure was selected to produce a moderate DAergic denervation ( 4,21 ), and for the purpose of comparison with previous data collected with n -3 PUFA-enriched diets ( 4 ).…”

“…Levels of autoradiographic labeling for Nurr1 and DAT in the SNpc were quantifi ed by computerized densitometry, as previously shown ( 4,21 ). Optical densities of the autoradiograms were translated into Ci/g of tissue using 14 C radioactivity standards (ARC 146-14 C standards, American Radiolabeled Chemical Inc., St. Louis, MO).…”

Kinetics and Mechanism of Reaction of cis-[Cr(C2O4)2(H2O)2]– with L-Dopa in Aqueous Medium: A Comparative Antiparkinsonian Studies

“…Parkinson disease is considered as the second most common neurodegenerative disorder [1]. The role of dopamine and its analogs in brain is significant and unquestionable.…”

Research on experimental models of neurodegenerative disorders and radiation-induced brain injury

“…PD, the second most common progressive neurodegenerative disorder after AD (Tanner & Goldman 1996), affects approximately 1% of the population older than 65 years (Gibrat et al 2009). …”