Objective: The main aim of the present study was to investigate whether behavioral and biochemical differences may occur between male and female old (12-month-old) transgenic A53T+/- and wild-type mice.

Background: Pathological hallmarks of Parkinson’s disease (PD) are loss of dopamine (DA) neurons with neuroinflammatory processes in the pars compacta of the substantia nigra (SNc) and in caudate-putamen (CPu), and missense mutations (e.g. A53T) in the α-synuclein gene. DA neuron degeneration leads to motor impairment, however PD also features a wide spectrum of autonomic manifestations including constipation, and displays a gender specificity since male are more affected than female.

Methods: Motor performance and coordination were evaluated by means of beam walking test. Time to traverse the beam, number of steps and errors per steps were recorded for each mouse. Stool frequency was evaluated by means of the one hours stool collection test, where dry weight and water content were determined from fecal pellets obtained during a 1 hour collection period. Immunohistochemical analysis of tyrosine hydroxylase (TH), as marker of DA neuron degeneration, glial fibrillary acidic protein (GFAP), as a marker of astroglia, and ionized calcium binding adaptor molecule-1 (Iba-1), as a marker of microglia, were evaluated in the SNc and CPu. Behavioral and biochemical experiments were carried out in both A53T+/- and wild-type male and female mice.

Results: A53T+/- male mice spent a significant longer time to traverse the beam, as compared with wild-type male and A53T+/- female mice. Moreover, the weight of the dry stool of A53T+/- male mice and the water content was lower, as compared with wild-type male mice and A53T+/- female mice. A significant increase of both GFAP- and Iba-1-positive cells was observed in the SNc and CPu of A53T+/- male mice, as compared with wild-type male and A53T+/- female mice. Moreover, A53T+/- male mice exhibited a significant loss of TH-positive neurons in the SNc, as compared with wild-type male and A53T+/- female mice.

Conclusions: Results showed that A53T+/- male mice may be more susceptible than female to the motor, autonomic and biochemical deficits that characterize PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/gender-dependent-behavioral-and-biochemical-differences-in-the-a53t-genetic-mouse-model-of-parkinsons-disease/