Objective: To determine the age-related changes in neuronal morphology in the substantia nigra pars compacta (SNpc) and Ventral Tegmental Area (VTA) of C57BL/6J and CD-1 mice.

Background: Epidemiological studies suggest that non-whites are less susceptible to Parkinson’s disease (PD) than the Caucasians. Since human tissues were not easily available for direct comparisons between susceptible and resistant populations, we compared resistant (CD-1) and vulnerable (C57BL/6J) mice strains, to study the phenomenon of differential susceptibility. The young C57BL/6J had fewer dopaminergic (DA) neurons than CD-1 and lost 50-60% of neurons to MPTP. Here we examined the morphology of SNpc and VTA neurons, at middle and old age.

Method: Both the strains (n=4-5/strain/experimental condition; male) were studied at two age-periods i.e. 10-12m (middle-aged) and 18-20m (old). They received either normal saline or 04 i.p. injections of MPTP-hydrochloride (15mg/kg) at 2-h intervals. TH immunohistochemistry was performed on midbrains, 7 days post-MPTP. Morphometric analysis e.g. soma and nuclear size/ratio and TH expression was performed on high magnification images captured using a “Windows” based image analysis system.

Results: The SNpc neurons of control CD-1 were significantly large and had high TH compared to those of C57BL/6J (*p<0.05); at middle age but reduced at old age and in response to MPTP. The C57BL/6J showed better attributes at old age in both SNpc and VTA (C57BL/6J vs CD-1;**p<0.01). C57BL/6J also showed higher nucleus-cytoplasmic ratio at middle age, in both SNpc (C57BL/6 vs CD-1; ***p<0.001) and VTA (C57BL/6 vs CD-1;**p<0.01); which reduced with aging and upon-MPTP.

Conclusion: The increased TH in SNpc neurons from middle to old age in CD-1 vis-à-vis C57BL/6J suggests enhanced enzymatic substrate to support DA functions in the former, a resilient strain. Albeit, the loss upon MPTP suggests presence of degenerative signals at old age. Contrarily, the enhanced TH and larger neurons in C57BL/6J-VTA suggests a compensation, both sub-regions. As the latter strain is known for persistent susceptibility, it might be critical to evaluate the total cell loss. Such region specific differences in DA neuronal responses may likely contribute to differential susceptibility between different ethnicities.

« Back to 2023 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/dopaminergic-neuronal-attributes-in-aging-substantia-nigra-and-ventral-tegmental-area-of-mice-strains-distinctly-sensitive-to-mptp/