Journal
NEUROCHEMISTRY INTERNATIONAL
Volume 126, Issue -, Pages 218-228Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuint.2019.03.020
Keywords
mGlus receptor; Aging; Neuroinflammation; Neurodegeneration; Huntington's disease
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Funding
- CNPq [429049/2018-8]
- FAPEMIG [PPM -00212-18]
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The growing elderly population world widely prompts the need for studies regarding aged brain and its susceptibility to neurodegenerative diseases. It has been shown that aged brain exhibits several alterations, including neuroinflammation, which prone this organ to neurodegenerative processes. Metabotropic glutamate receptor 5 (mGlu(5) receptor) has a role in neuronal cell loss and inflammation. Although the relevance of mGlu(5) receptor in different diseases has been investigated, its involvement in normal brain aging remains unclear. In the present study, we used the mGlu(5) receptor knockout (mGluR5(-/-)) mice, a model of Huntington's Disease (BACHD), and the double mutant mice (mGluR5(-/-)/BACHD), at the ages of 2, 6 and 12 months, to investigate whether mGlu(5) receptor has a role in brain aging. We demonstrated that mGluR5(-/-) mice exhibit diminished number of neurons at 12 months of age in the cortex and striatum, similarly to what was observed in the case of BACHD and mGluR5(-/-)/BACHD mice. In addition, ablation of mGlu(5) receptor increased the number of astrocytes and microglia in BACHD and wild type (WT) mice in an age-dependent manner in the cortical region, but not in the striatum. Interestingly, 12-month-old mGluR5(-/-) mice induced microglia activation, evidenced by increased CD68 expression and diminished number of microglia ramifications in skeleton analyses. Importantly, the presence of mutant huntingtin and the absence of mGlu(5) receptor promoted decreased levels of fractalkine expression in aged mice, which could account for the decreased levels of microglia activation in these mice. Together, our data provide evidence that mGlu(5) receptor plays a role in brain aging by modulating different cell types in the central nervous system (CNS).
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