Abstract
Old age is a risk factor for Alzheimer’s disease (AD), which is characterized by hippocampal impairment together with substantial changes in glial cell functions. Are these alterations due to the disease progression or are they a consequence of aging? To start addressing this issue, we studied the expression of specific astrocytic and microglial structural and functional proteins in a validated transgenic model of AD (3×Tg-AD). These mice develop both amyloid plaques and neurofibrillary tangles, and initial signs of the AD-like pathology have been documented as early as three months of age. We compared male 3×Tg-AD mice at 6 and 12 months of age with their wild-type age-matched counterparts. We also investigated neurons by examining the expression of both the microtubule-associated protein 2 (MAP2), a neuronal structural protein, and the brain-derived neurotrophic factor (BDNF). The latter is indeed a crucial indicator for synaptic plasticity and neurogenesis/neurodegeneration. Our results show that astrocytes are more susceptible to aging than microglia, regardless of mouse genotype. Moreover, we discovered significant age-dependent alterations in the expression of proteins responsible for astrocyte–astrocyte and astrocyte–neuron communication, as well as a significant age-dependent decline in BDNF expression. Our data promote further research on the unexplored role of astroglia in both physiological and pathological aging.
Highlights
Alzheimer’s disease (AD) is currently considered a multifactorial disorder, aging still remains its greatest risk factor (van der Flier and Scheltens, 2005; Hodson, 2018)
We explored the hippocampal expression of glial fibrillary acidic protein (GFAP) and S100B for astrocytes, and the ionized calcium binding adaptor molecule-1 (Iba1) and the cluster of differentiation 11b/c (CD11b/c) for microglia
We observed a significant reduction of the cytoskeletal protein GFAP and the neurotrophin S100B in 12-month-old mice compared with 6-month-old mice, irrespective of genotype (Figure 1A, B, C)
Summary
Alzheimer’s disease (AD) is currently considered a multifactorial disorder, aging still remains its greatest risk factor (van der Flier and Scheltens, 2005; Hodson, 2018). Glia represents one of them because of its contribution in the regulation of several highly specialized brain functions including glutamate, ions and water homeostasis, excitability and metabolic support of neurons, synaptic plasticity, brain blood flow, and neurotrophic support (Acosta et al, 2017; Bronzuoli et al, 2017). These functions are well integrated since astrocytes tightly communicate one to each other through gap junctions, comprised mainly of connexin-43 (CX43), that provide the structural basis for astrocyte networks (Bruzzone et al, 1996; Theis et al, 2005). When such a clearance is dysfunctional, Aβ deposition occurs facilitating neurodegeneration (Iliff et al, 2012)
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