Astrocytes in the aging brain

Cotrina, Maria Luisa; Nedergaard, Maiken

doi:10.1002/jnr.10121.abs

Cited by 44 publications

(58 citation statements)

References 19 publications

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“…In contrast to the pattern of widespread loss of glia and neurons in the myenteric plexus of the autonomic nervous system of healthy aged rats that we have observed, it is currently accepted that healthy aging of the CNS is not characterized by significant and widespread neuronal death (compare with Peters 2002) or dramatic changes in glial populations (Unger 1998, Cotrina andNedergaard 2002). Interestingly, the changes that we report for the ENS of ad-libitum-fed aged rats are similar to those seen in the CNS of Alzheimer's disease patients, and not healthy-aged individuals.…”

Section: Discussioncontrasting

confidence: 89%

Loss of glia and neurons in the myenteric plexus of the aged Fischer�344 rat

2004

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Over the normal lifespan, a subpopulation of myenteric neurons in the small and large intestines dies. This loss is one possible mechanism for the disruptions of gastrointestinal function seen in the elderly. Little, however, is known about how the glia constituting the supportive cells of the myenteric plexus may change with aging and the losses of the enteric neurons. The goal of the present study, therefore, was to determine what, if any, changes occur in the glia associated with myenteric neurons in the aged gut. Two experimental groups, consisting of adult (5-6 months of age, n = 8) or aged (26 months of age, n = 8) virgin male Fischer 344 rats, fed ad libitum, were examined. The duodenum, jejunum, ileum, colon, and rectum from each rat were prepared as whole mounts, and indirect immunofluorescence was used to visualize the myenteric glia and neurons (antibodies to S-100 and the HuC/D protein, respectively). Separate counts of glia and neurons from the same specimens were determined, and these counts were expressed both as per ganglionic area and as per ganglion to correct for "dilution" effects resulting from age-associated changes in tissue area. Significant reductions in both the numbers of glia as well as neurons occurred in every region of the small and large intestine sampled from aged rats, except for the rectum, where a nonsignificant decrease was observed. Glial loss was proportional to neuronal death, suggesting an interdependency between the two cell types. Thus, an understanding of the nature of the neuron-glia interaction in the enteric nervous system may provide insight into the deterioration of function seen in the aged gut.

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Section: Discussioncontrasting

confidence: 89%

Loss of glia and neurons in the myenteric plexus of the aged Fischer�344 rat

2004

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“…Typically, a reactive astrocyte is produced after challenging with different kinds of insults and is a characteristic of many neuropathologies, including Alzheimer's disease (Blasko et al 2004;Seth and Koul 2008). Reactive astrocytes are also a hallmark of aging (Cotrina and Nedergaard 2002;Hayakawa et al 2007), probably consequent to the inflammatory and oxidative state of the aging brain (Godbout and Johnson 2006;Yankner et al 2008). Besides supporting the validity of our experimental model for the study of brain aging, the presence of reactive astrocytes may be responsible for the increased expression of IGF1-R by neurons.…”

Section: Discussionsupporting

confidence: 63%

Astrocytes Regulate the Expression of Insulin-Like Growth Factor 1 Receptor (IGF1-R) in Primary Cortical Neurons During In Vitro Senescence

et al. 2009

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The role of insulin-like growth factor 1 (IGF1) pathway as regulator of aging and age-related diseases is increasingly recognized. Recent evidence has been provided that neuronal IGF1-R increases during aging leading to activation of a signaling pathway that causes an increased production of amyloid beta-peptide, the principal event in the pathogenesis of Alzheimer's disease. Here, by using long-term neuronal cultures as a model of aging, we show that astroglial cells are required to upregulate the expression of IGF1-R in neurons during in vitro senescence. Moreover, evidence is provided that the cross-talk between astrocytes and neurons is independent of cell-to-cell contact, and it is mediated by low molecular weight soluble factor(s) released by astrocytes in culture medium. These results suggest that astrocytes could play an important role in aging and age-related pathological processes.

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“…Parenthetically, recent evidence has suggested that overexpression of either or both of S100B and GFAP in reactive astrocytes may have pathogenic roles in chronic brain pathologies, such as post-stroke dementia, aging, and neurodegenerative diseases [30, 231,232]. Overexpression of S100B has been shown to alter synaptic plasticity and impair spatial learning in transgenic mice, effects attributable to decreased long-term potentiation [233,234].…”

Section: Discussionmentioning

confidence: 99%

Arundic Acid (ONO-2506) Ameliorates Delayed Ischemic Brain Damage by Preventing Astrocytic Overproduction of S100B

et al. 2005

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After focal cerebral ischemia, the infarct volume increases rapidly within acute infarct expansion (initial 12 to 24 h) and continues slowly during delayed infarct expansion (25 to 168 h). While acute infarct expansion represents progressive necrosis within the ischemic core, delayed infarct expansion starts as disseminated apoptotic cell death in a narrow rim surrounding the infarct border, which gradually coalesces to form a larger infarct. Discovery of a distinct correlation between reactive astrogliosis along the infarct border and delayed infarct expansion in the rodent ischemia model led us to investigate the possible causal relationship between the two events. Specifically, the calcium binding protein S100B exerts detrimental effects on cell survival through activation of various intracellular signaling pathways, resulting in altered protein expression. Arundic acid [(R)-(-)-2-propyloctanoic acid, ONO-2506] is a novel agent that inhibits S100B synthesis in cultured astrocytes. In the rodent ischemia model, this agent was shown to inhibit both the astrocytic overexpression of S100B and the subsequent activation of signaling pathways in the peri-infarct area. Concurrently, delayed infarct expansion was prevented, and neurologic deficits were promptly ameliorated. The results of subsequent studies suggest that the efficacy of arundic acid is mediated by restoring the activity of astroglial glutamate transporters via enhanced genetic expression.

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Astrocytes in the aging brain

Cited by 44 publications

References 19 publications

Loss of glia and neurons in the myenteric plexus of the aged Fischer�344 rat

Loss of glia and neurons in the myenteric plexus of the aged Fischer�344 rat

Astrocytes Regulate the Expression of Insulin-Like Growth Factor 1 Receptor (IGF1-R) in Primary Cortical Neurons During In Vitro Senescence

Arundic Acid (ONO-2506) Ameliorates Delayed Ischemic Brain Damage by Preventing Astrocytic Overproduction of S100B

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