Acute Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or Paraquat on Core Temperature in C57BL/6J Mice

Abstract

Background: MPTP and paraquat are two compounds that have been used to model Parkinson’s disease in mice. Previous studies in two non-traditional strains of mice have shown that a single dose of MPTP can induce changes in body temperature, while the effects of paraquat have not been examined. Examination of body temperature is important since small fluctuations in an animal’s core temperature can significantly affect drug metabolism, and if significant enough can even culminate in an animal’s death.Objective: To determine how external heating can alter the survival of C57BL/6J mice following MPTP administration.Methods: In this study, we examine the effects of MPTP (4×20 mg/kg, 2 hours apart) and paraquat (2×10 mg/kg/week for 3 weeks) on core temperature of C57BL/6J mice. Correlations of purine and catecholamine levels were also done in mice treated with MPTP.Results: We find that MPTP induces a significant hypothermia in C57BL/6J mice that reduces their core temperature below the limit of fatal hypothermia. Unlike MPTP, paraquat did not induce a significant hypothermia. Placement of animals on heating pads significantly abrogates the loss of core temperature. In both heated and non-heated conditions, mice treated with MPTP showed a significant depletion of ATP within 2 hours of administration in both striatum and SN that started to recover 2 hours after MPTP administration was complete. Striatal DA and DOPAC are significantly reduced starting 4–6 hours after MPTP.Conclusions: The fatal hypothermic effects of MPTP can be abrogated through use of external heating.

Comparative analysis of dose-dependent neurotoxic response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in C57BL/6 N mice derived from three different sources

“…Administering acute MPTP regimens suitable for inducing stable and reproducible lesions of parkinsonism or parkinsonian syndrome showed that MPTP caused a rapid reduction in BW and a hypothermic effect in a dose-dependent manner, and unexpectedly high mortality rates in mice (at MPTP 20 mg/kg or higher) due to profound hypothermia in the absence of external heat support in a preliminary study (data not shown). These results are consistent with previous studies that reported hypothermic responses and sensitivity induced by unknown malfunctional cellular mechanisms, suggesting the need for external heat support in MPTP-induced PD mouse modeling [6].…”

“…To this end, rodent models for PD, particularly C57BL/6 mice, have been widely used to unravel various pathological events and explore therapeutic mechanisms, although humans and primates are the gold standard of PD research [3,4]. Over the years, with numerous efforts to develop a PD model in mice, the exogenous administration of a variety of neurotoxic materials such as 6-hydroxydopamine, paraquat, rotenone, and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) have been used to induce DA loss to replicate PD symptoms, collectively called parkinsonism and/or parkinsonian syndrome [5][6][7]. Among the various pharmacological PD models, the MPTP-induced PD model has been most commonly used for several reasons: similar clinical symptoms to those in patients with PD, no requirements for experimental technology, and reliable and reproducible lesions in the nigrostriatal dopaminergic pathway [3,8].…”

Assessment of the Effects of MPTP and Paraquat on Dopaminergic Neurons and Microglia in the Substantia Nigra Pars Compacta of C57BL/6 Mice

“…MPTP dose volumes were 2.5 mL/kg/dose at WIL and 4 mL/kg/dose at SJCRH. Shoebox bin cages housing MPTP-treated animals housed at both SJCRH and WIL were placed on heating pads for 24 hours after dosing in order to maintain animal viability [25]. …”

In vitro modeling of the neurovascular unit: advances in the field

“…High cell viability was found to be maintained up to 21 days in the spheroid model containing six cell types, which is useful in evaluating long term effects of drug toxicity [104]. Expression of P-gp and GLUT-1 proteins were also identified as these proteins have a pivotal role in expelling unwanted chemical from the brain tissue and transport glucose into the brain tissue respectively and abnormalities in these proteins lead to different diseases [104][105][106][107]. Expression of tight junctions, adherens junctions, and proteins associated with adherens junction was also identified to avert the free paracellular diffusion of substances into the brain parenchyma.…”