Astrocyte changes in aging cerebral cortex and hippocampus: A quantitative immunohistochemical study (original) (raw)
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Complex and region-specific changes in astroglial markers in the aging brain
Neurobiology of aging, 2014
Morphological aging of astrocytes was investigated in entorhinal cortex (EC), dentate gyrus (DG), and cornu ammonis 1 (CA1) regions of hippocampus of male SV129/C57BL6 mice of different age groups (3, 9, 18, and 24 months). Astroglial profiles were visualized by immunohistochemistry by using glial fibrillary acidic protein (GFAP), glutamine synthetase (GS), and s100b staining; these profiles were imaged using confocal or light microscopy for subsequent morphometric analysis. GFAP-positive profiles in the DG and the CA1 of the hippocampus showed progressive age-dependent hypertrophy, as indicated by an increase in surface, volume, and somata volume at 24 months of age compared with 3-month-old mice. In contrast with the hippocampal regions, aging induced a decrease in GFAP-positive astroglial profiles in the EC: the surface, volume, and cell body volume of astroglial cells at 24 months of age were decreased significantly compared with the 3-month group. The GS-positive astrocytes displayed smaller cellular surface areas at 24 months compared with 3-month-old animals in both areas of hippocampus, whereas GS-positive profiles remained unchanged in the EC of old mice. The morphometry of s100b-immunoreactive profiles revealed substantial increase in the EC, more moderate increase in the DG, and no changes in the CA1 area. Based on the morphological analysis of 3 astroglial markers, we conclude that astrocytes undergo a complex age-dependent remodeling in a brain regionespecific manner.
Aging impairs astrocytes in the human cerebral cortex
How aging affects cellular components of the human brain active milieu remains largely unknown. We analyzed astrocytes and neurons in the neocortical access tissue of younger (22 - 50 years) and older (51 - 72 years) adult patients who underwent glioma resection. Aging decreased the amount of reduced mitochondrial cytochromes in astrocytes but not neurons. The total amount of protein was decreased in astrocytes and increased in neurons. Aged astrocytes showed morphological dystrophy quantified by the decreased length of branches, decreased volume fraction of leaflets, and shrinkage of the anatomical domain. Dystrophy correlated with the loss of gap junction coupling between astrocytes and increased input resistance. Aging was accompanied by the upregulation of glial fibrillary acidic protein (GFAP) and downregulation of membrane-cytoskeleton linker Ezrin associated with leaflets. No significant changes in neuronal excitability or spontaneous inhibitory postsynaptic signaling were ob...
Mechanisms of Ageing and Development, 1999
Age-related changes of glial fibrillary acidic protein (GFAP) immunoreactivity were investigated in the cerebellar cortex of young (3 months), adult (12 months) and old (24 months) rats using immunohistochemical techniques associated with image analysis. In young rats, cell bodies of GFAP-immunoreactive astrocytes were found in the white matter and in the granular layer of cerebellar cortex. Radially-oriented branches of astrocytes which are sited in the granular layer were also observed in the molecular layer. The number of GFAP-immunoreactivity astrocytes of white matter was decreased in adult and old rats in comparison with young cohorts, whereas their size increased progressively from 3 to 24 months old. The number and the size of GFAP-immunoreactive astrocytes of the granular layer was similar in young and adult rats. An increased number and size of GFAP-immunoreactive astrocytes was noticeable in old rats in comparison with younger cohorts. The number of radially oriented branches of the molecular layer was the same in the three age groups investigated. The above results indicate that GFAP-immunoreactive astrocytes of rat : S 0 0 4 7 -6 3 7 4 ( 9 9 ) 0 0 0 0 8 -1 M. Sabbatini et al. / Mechanisms of Ageing and De6elopment 108 (1999) 165-172 166 cerebellar cortex undergo age-related changes. The not homogeneous sensitivity to aging of cerebellar astrocytes suggests that evaluation of changes of different cell populations of cerebellar cortex should represent an important step of research on aging cerebellum.
2016
Ageing is accompanied by a decline in cognitive functions; along with a variety of neurobiological changes. The association between inflammation and ageing is based on complex molecular and cellular changes that we are only just beginning to understand. The hippocampus is one of the structures more closely related to electrophysiological, structural and morphological changes during ageing. In the present study we examined the effect of normal ageing and LPS-induced inflammation on astroglia-neuron interaction in the rat hippocampus of adult, normal aged and LPS-treated adult rats. Astrocytes were smaller, with thicker and shorter branches and less numerous in CA1 Str. radiatum of aged rats in comparison to adult and LPS-treated rats. Astrocyte branches infiltrated apoptotic neurons of aged and LPS-treated rats. Cellular debris, which were more numerous in CA1 of aged and LPS-treated rats, could be found apposed to astrocytes processes and were phagocytated by reactive microglia. Rea...
Neuroglia in ageing and disease
Cell and Tissue Research, 2014
The proper operation of the mammalian brain requires dynamic interactions between neurones and glial cells. Various types of glial cells are susceptible to morphofunctional changes in a variety of brain pathological states, including toxicity, neurodevelopmental, neurodegenerative and psychiatric disorders. Morphological modifications include a change in the glial cell size and shape; the latter is evident by changes of the appearance and number of peripheral processes. The most blatant morphological change is associated with the alteration of the sheer number of neuroglia cells in the brain. Functionally, glial cells can undergo various metabolic and biochemical changes, the majority of which reflect upon homeostasis of neurotransmitters, in particular that of glutamate, as well as on defence mechanisms provided by neuroglia. Not only glial cells exhibit changes associated with the pathology of the brain but they also change with brain aging.
Brain Research, 2000
Reactive astrocytosis is a well known phenomenon that occurs in the normal aging process of the brain. While many studies indicate astrocytic hypertrophy and glial fibrillary acidic protein (GFAP) content increase with age in the hippocampal formation of certain animal models, it is unclear whether these findings are generalizable to the primate and to other areas of the brain. In this study, we quantitatively assessed age-related changes in astrocytic cell size and density in a rhesus monkey model of normal aging. By GFAP immuno-1 histochemistry, we observed an increase in GFAP cell size but not density in all subcortical white matter areas of the frontal, temporal, and parietal cortices. No significant increases in astrocyte hypertrophy were observed in any gray matter area examined. In addition, Western blotting experiments showed increases in total and degraded GFAP content with age, suggesting altered degradation and possibly production of GFAP occur with age.
Plos One, 2012
Ageing is accompanied by a decline in cognitive functions; along with a variety of neurobiological changes. The association between inflammation and ageing is based on complex molecular and cellular changes that we are only just beginning to understand. The hippocampus is one of the structures more closely related to electrophysiological, structural and morphological changes during ageing. In the present study we examined the effect of normal ageing and LPS-induced inflammation on astroglia-neuron interaction in the rat hippocampus of adult, normal aged and LPS-treated adult rats. Astrocytes were smaller, with thicker and shorter branches and less numerous in CA1 Str. radiatum of aged rats in comparison to adult and LPS-treated rats. Astrocyte branches infiltrated apoptotic neurons of aged and LPS-treated rats. Cellular debris, which were more numerous in CA1 of aged and LPS-treated rats, could be found apposed to astrocytes processes and were phagocytated by reactive microglia. Reactive microglia were present in the CA1 Str. Radiatum, often in association with apoptotic cells. Significant differences were found in the fraction of reactive microglia which was 40% of total in adult, 33% in aged and 50% in LPS-treated rats. Fractalkine (CX3CL1) increased significantly in hippocampus homogenates of aged and LPS-treated rats. The number of CA1 neurons decreased in aged rats. In the hippocampus of aged and LPS-treated rats astrocytes and microglia may help clearing apoptotic cellular debris possibly through CX3CL1 signalling. Our results indicate that astrocytes and microglia in the hippocampus of aged and LPS-infused rats possibly participate in the clearance of cellular debris associated with programmed cell death. The actions of astrocytes may represent either protective mechanisms to control inflammatory processes and the spread of further cellular damage to neighboring tissue, or they may contribute to neuronal damage in pathological conditions.
Cellular Composition in the Aging Cerebral Cortex of Humans
Neurophysiology, 2019
The numbers/densities of neurons and gliocytes and the neuron-to-glia ratios were calculated in different layers of the cerebral cortex of three subjects in a post mortem study. The subjects were 60 to 70 years old (which was qualified as a relatively early period of aging) and had no history of neurodegeneration diseases. The brains embalmed in 10% formalin-fixative solution were processed, and coronal 4-µmthick slices of tissues of the frontal, parietal, temporal, and occipital lobes were prepared and stained with hematoxylin-eosin. Clear cortical lamination was observed in all lobes. In the frontal lobe, the mean neuron density (number of neurons within visual fields at a 400× magnification) was significantly higher, while that of gliocytes was significantly lower compared to the respective values in other lobes (P < 0.05). A significant association between the number of neurons and glia was found in the frontal lobe (r 2 = 0.40, P = 0.0029) and in all superficial cortical layers (r 2 = 0.72, P = 0.0025), but not in the deeper layers (r 2 = 0.18, P = 0.14). The mean neuron-to-glia ratio in different lobes and layers varied from 1.0 : 0.81 to 1.0 : 3.54. It is concluded that, in early-aging subjects with no cerebral pathology, the quantitative characteristics of cortical neurons and glial cells do not differ significantly from those in the brains of younger adult healthy subjects.
Frontiers in Pharmacology, 2019
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.
Glial fibrillary acidic protein immunoreactive astrocytes in developing rat hippocampus
Mechanisms of ageing and development, 2002
The developmental pattern of glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes was investigated in the hippocampus (subfields CA1, CA3 and CA4) and in the dentate gyrus of male and female rats aged 11, 16, 30, 90 and 150 days by immunohistochemistry associated with image analysis. Analysis was centred on stratum radiatum, a hippocampal area rich in GFAP-immunoreactive astrocytes. The volume of different portions of hippocampus, the number and the size of astrocytes, the intensity of cell body GFAP immunostaining as well as the extension of astrocyte were assessed. A maturation pattern consisting in higher cellular expression of GFAP, an increase in overall cell size and expanding arborisation from the 11th to the 30th postnatal day, followed by stabilisation of these parameters until the 90th day of life, and a subsequent decrease in the oldest age group studied was found. A sex-related different temporal pattern of astrocytes maturation in size and GFAP content was o...