RESUMEN
The COVID-19 pandemic imposed a series of behavioral changes that resulted in increased social isolation and a more sedentary life for many across all age groups, but, above all, for the elderly population who are the most vulnerable to infections and chronic neurodegenerative diseases. Systemic inflammatory responses are known to accelerate neurodegenerative disease progression, which leads to permanent damage, loss of brain function, and the loss of autonomy for many aged people. During the COVID-19 pandemic, a spectrum of inflammatory responses was generated in affected individuals, and it is expected that the elderly patients with chronic neurodegenerative diseases who survived SARSCoV-2 infection, it will be found, sooner or later, that there is a worsening of their neurodegenerative conditions. Using mouse prion disease as a model for chronic neurodegeneration, we review the effects of social isolation, sedentary living, and viral infection on the disease progression with a focus on sickness behavior and on the responses of microglia and astrocytes. Focusing on aging, we discuss the cellular and molecular mechanisms related to immunosenescence in chronic neurodegenerative diseases and how infections may accelerate their progression.
RESUMEN
We investigated long-term environmental influences on morphology of microglia from the outer and middle thirds of molecular layer of the dentate gyrus (MolDG), and on microglia from dorsal and ventral dentate gyrus molecular layer. We also estimated the total number of MolDG microglia using stereology. For this purpose, microglia of the molecular layer of the dentate gyrus of 20-month-old female Swiss albino mice, housed from 21st postnatal day onwards, in the impoverished environment of the standard laboratory cages (SEA), or in a cage with an enriched environment (EEA), were reconstructed microscopically in three dimensions and compared with each other and with microglia of 6-month-old female Swiss albino mice, also housed from weaning onwards in an enriched cage (EEY). All mice had their brains sectioned and processed for immunolabeling for IBA-1, a selective microglia marker. Random and systematic microglia samples were reconstructed in three dimensions and classified morphologically using hierarchical cluster analysis, followed by discriminant function analysis. SEA and EEY showed two morphological phenotypes of microglia in both the outer and middle thirds of MolDG. EEA mice showed such a reduction in the morphological diversity of microglia that essentially a single morphotype was found. EEA mouse microglia showed an intermediate morphological complexity between types I and II SE microglia. We suggest that type I and type II microglia in SE mice may have different physiological roles and that long-term EE may be associated with adaptive responses of microglial phenotypes to somatomotor and cognitive stimuli.
