Abstract
Little is known about age‐dependent changes in structure and function of astrocytes and of the impact of these on the cognitive decline in the senescent brain. The prevalent view on the age‐dependent increase in reactive astrogliosis and astrocytic hypertrophy requires scrutiny and detailed analysis. Using two‐photon microscopy in conjunction with 3D reconstruction, Sholl and volume fraction analysis, we demonstrate a significant reduction in the number and the length of astrocytic processes, in astrocytic territorial domains and in astrocyte‐to‐astrocyte coupling in the aged brain. Probing physiology of astrocytes with patch clamp, and Ca2+ imaging revealed deficits in K+ and glutamate clearance and spatiotemporal reorganisation of Ca2+ events in old astrocytes. These changes paralleled impaired synaptic long‐term potentiation (LTP) in hippocampal CA1 in old mice. Our findings may explain the astroglial mechanisms of age‐dependent decline in learning and memory.
Highlights
The ageing of the brain represents the lifelong adaptation of this exceptionally complex organ to the “exposome” interacting with the genetic background
Astrocytic ageing remains rather poorly characterised; neither structure nor function of old astrocytes have been analysed in depth
Investigations frequently described an increase in central nervous system (CNS) expression of glial fibrillary acidic protein (GFAP) in rodents (Goss et al, 1991; Kohama et al, 1995; Nichols et al, 1993) and humans (David et al, 1997)
Summary
The ageing of the brain represents the lifelong adaptation of this exceptionally complex organ to the “exposome” (cumulative exposure of an individual to environmental factors during the lifetime) interacting with the genetic background. Astrocytic ageing remains rather poorly characterised; neither structure nor function of old astrocytes have been analysed in depth It is generally agreed, based on stereological and immunohistochemical studies, that the total number of astrocytes in the central nervous system (CNS) of rodents, primates and humans do not significantly change with age (Fabricius et al, 2013; Olabarria et al, 2010; Pelvig et al, 2008; Robillard et al, 2016). Our results demonstrate a decrease in astrocytic domain size, volume fraction of perisynaptic processes and astrocyte coupling through gap junctions in the ageing; this, in turn, affects K+ buffering and glutamate clearance by astrocytes, and astrocytic Ca2+ signalling, which all impact on synaptic plasticity and affect long-term potentiation in hippocampal synapses
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