Gender Differences in Neurodegeneration, Neuroinflammation and Na+-Ca2+ Exchangers in the Female A53T Transgenic Mouse Model of Parkinson’s Disease

Frontiers in Aging Neuroscience

Marcello Serra¹  Giulia Costa¹  Antonio Feliciello²  Maria Jose Sisalli³  Salvatore Della Notte³  Antonella Scorziello³  Nicola Simola⁴  Maria Antonietta Casu⁵  Micaela Morelli⁶  Annalisa Pinna⁶  Lucio Annunziato⁷ 

[1] Department of Biomedical Sciences, Section of Neuroscience, University of Cagliari, Cagliari, Italy;Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Naples, Italy;Department of Neuroscience, Reproductive and Odontostomatological Sciences, University of Naples Federico II, Naples, Italy;National Institute of Neuroscience (INN), University of Cagliari, Cagliari, Italy;National Research Council of Italy, Institute of Translational Pharmacology, UOS of Cagliari, Scientific and Technological Park of Sardinia POLARIS, Pula, Italy;National Research Council of Italy, Neuroscience Institute, Cagliari, Italy;SDN Research Institute Diagnostics and Nuclear (IRCCS SDN), Naples, Italy;

关键词: constipation;    dopamine;    GFAP;    IBA-1;    memory;    midbrain;   

DOI  :  10.3389/fnagi.2020.00118

来源: DOAJ

【 摘 要 】

Twelve-month-old male mice expressing the human A53T variant of α-synuclein (A53T) develop dopamine neuron degeneration, neuroinflammation, and motor deficits, along with dysfunctions of the mitochondrial Na+-Ca2+ exchanger (NCX) isoforms 1 (NCX1) and 3 (NCX3) in the nigrostriatal system. Since gender is thought to play a role in the etiology of Parkinson’s disease (PD), we characterized neurochemical and behavioral alterations in 12-month-old female A53T transgenic mice. We investigated the presence of dopaminergic degeneration, astrogliosis and microgliosis using immunohistochemistry for tyrosine hydroxylase (TH), glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule-1 (IBA-1) in both the substantia nigra pars compacta (SNc) and striatum. In the same regions, we also evaluated the co-localization of NCX1 in cells positive for IBA-1 and the co-localization of NCX3 in TH-positive neurons and fibers. Furthermore, in both male and female mice, we performed motor (beam walking and pole tests) and memory [novel object recognition (NOR) and spontaneous alternation] tasks, together with tests to evaluate peripheral deficits (olfactory and stool collection tests). Female A53T transgenic mice displayed degeneration of nigral dopaminergic neurons, but neither microgliosis nor astrogliosis in the SNc and striatum. Moreover, female A53T transgenic mice displayed co-localization between NCX1 and IBA-1 positive cells in the striatum but not SNc, whereas NCX3 did not co-localize with either TH-positive terminals or neuronal bodies in the nigrostriatal system. Furthermore, female A53T transgenic mice showed increased crossing time in the beam walking test, but no impairments in the pole or memory tests, and in tests that evaluated peripheral deficits, whereas male A53T transgenic mice displayed motor, memory and peripheral deficits. Immunohistochemical and behavioral results obtained here in the female mice differ from those previously observed in males, and suggest a dissimilar influence of NCX1 and NCX3 on dopaminergic function in female and male A53T transgenic mice, strengthening the validity of these mice as a model for studying the etiological factors of PD.

【 授权许可】

Unknown