Elsevier

Neuroscience

Volume 323, 26 May 2016, Pages 170-182
Neuroscience

Review
Astrocytes in physiological aging and Alzheimer’s disease

https://doi.org/10.1016/j.neuroscience.2015.01.007Get rights and content

Highlights

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    Astrocytes are fundamental for homoeostasis, defence and regeneration of the CNS.

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    In Alzheimer’s disease (AD) astrocytes undergo degeneration and atrophy.

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    Atrophy of astrocytes alters homeostatic reserve of the brain.

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    Astrocytes can be regulated through environmental stimulation and/or medication.

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    Astrocytes can be targeted for prevention and cure of neurodegenerative disorders.

Abstract

Astrocytes are fundamental for homoeostasis, defence and regeneration of the central nervous system. Loss of astroglial function and astroglial reactivity contributes to the aging of the brain and to neurodegenerative diseases. Changes in astroglia in aging and neurodegeneration are highly heterogeneous and region-specific. In animal models of Alzheimer’s disease (AD) astrocytes undergo degeneration and atrophy at the early stages of pathological progression, which possibly may alter the homeostatic reserve of the brain and contribute to early cognitive deficits. At later stages of AD reactive astrocytes are associated with neurite plaques, the feature commonly found in animal models and in human diseased tissue. In animal models of the AD reactive astrogliosis develops in some (e.g. in the hippocampus) but not in all regions of the brain. For instance, in entorhinal and prefrontal cortices astrocytes do not mount gliotic response to emerging β-amyloid deposits. These deficits in reactivity coincide with higher vulnerability of these regions to AD-type pathology. Astroglial morphology and function can be regulated through environmental stimulation and/or medication suggesting that astrocytes can be regarded as a target for therapies aimed at the prevention and cure of neurodegenerative disorders.

Section snippets

Physiological and pathological brain aging

“There is no reason to suppose that protoplasm, the living material of organisms, has a necessarily limited duration of life, provided that the conditions proper to it are maintained, and it has been argued that since every living organism comes into existence as a piece of the protoplasm of the pre-existing living organism, protoplasm is potentially immortal” (Encyclopedia Britannica, 1911, 11th edition, v. 16, p. 974). Notwithstanding this optimistic assertion, multicellular organisms are

Neuroglia: the housekeeper and the protector

The maintenance of homeostasis of the CNS as well as its defence are the fundamental functions of neuroglia (Reichenbach and Bringmann, 2010, Kettenmann and Ransom, 2013, Verkhratsky and Butt, 2013). The neuroglia is represented by highly heterogeneous cell types optimized for numerous homeostatic functions. The oligodendrocytes, for example, enwrap axons with the myelin sheath and provide them with a local metabolic, structural and homeostatic support (Walhovd et al., 2014), whereas the NG-2

Astrogliopathology: the general concept

Dysfunction of neuroglia ultimately results in the failure of CNS homeostasis and compromises defensive capabilities of neural tissue. Hence, the gliopathology is an essential component of the most, and probably all, neurological diseases. The resolution of neuropathology is similarly directly linked to the ability of glia to limit the lesion, remove the pathogens and post-lesion cellular debris and permit and facilitate regeneration.

The concept of astrogliopathology is still in the nascent

Astrocytes in physiological aging

A coherent concept of neuroglial aging has not yet emerged. Morphometric studies, however, have demonstrated that two types of glia, the oligodendrocytes and the microglia, are most affected by physiological aging. The white matter seems to be the most affected in aging with ∼11% reduction in the volume (compared with only 3% reduction in the cortical volume (Haug and Eggers, 1991)). Cell counts in the human brain showed a very significant (∼30% or even more) decline in the number of

Astrogliosis

The pathological potential of neuroglia in the context of AD has been realized already by Alois Alzheimer, who observed glial cells in close association with damaged neurones; he also found that glial cells where obligatory components of senile plaques (Alzheimer, 1910); similarly, reactive astrocytes are present in the brains of AD animal models. In the AD both reactivity and atrophic changes in astrocytes occur (Fig. 2), and, moreover, glial changes often precede formation of specific

Neuroglia as a potential therapeutic target

Pathological remodeling of astrocytes that affects their homeostatic and neuroprotective functions is an important component of pathogenesis of neurodegenerative diseases including AD. This pathological potential of astrocytes makes them legitimate and auspicious therapeutic targets. The development of glia-aiming drugs remains in a nascent state, and indeed identifying glia-specific and therapeutically relevant molecules representing the largest challenge. Nonetheless astrocytes can be

Acknowledgments

Authors research was supported by Alzheimer’s Research Trust (UK) Programme Grant (ART/PG2004A/1) to A.V. and J.J.R.; by National Institutes of Health (The Eunice Kennedy Shriver National Institute of Child Health and Human Development award HD078678) to V.P., by the grants P3 310, J3 4051, J3 3632, J3 6790 and J3 4146 from the Slovenian Research Agency (ARRS) and the EduGlia ITN EU grant to R.Z. and A.V., and by Plan Nacional de I+D+I 2008–2011 and ISCIII-Subdirección General de Evaluación y

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