Glial reaction in the hippocampal formation is highly correlated with aging in human brain

David, Jean‐Philippe; Ghozali, Farida; Fallet-Bianco, Catherine; Wattez, A.; Delaine, Stephanie Clisant; Boniface, B.; Menza, C. Di; Delacourte, André

doi:10.1016/s0304-3940(97)00708-8

Cited by 125 publications

(91 citation statements)

References 15 publications

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“…Our results indicate astrocyte hypertrophy in both cerebellum and frontal lobe of aged compared to young monkeys, as shown by GFAP immunostaining. These results are in agreement with previous reports showing increased GFAP in the human entorhinal cortex and in the hippocampus with aging [21] and in the hippocampus and striatum of aged rats [37]. cPLA 2 and COX-2 enzymes have been shown to be localized at post-synaptic sites in neurons [12,28,39] where they are involved in the stimulatory activity of excitatory neurons.…”

Section: Discussionsupporting

confidence: 93%

Regional protein levels of cytosolic phospholipase A2 and cyclooxygenase-2 in Rhesus monkey brain as a function of age

Weerasinghe

Coon

Bhattacharjee

et al. 2006

Brain Research Bulletin

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Limited evidence suggests that brain cytosolic phospholipase A 2 (cPLA 2 ), which selectively releases arachidonic acid (AA) from membrane phospholipids, and cyclooxygenase-2 (COX-2), the ratelimiting enzyme for AA metabolism to prostanoids, change as a function of normal aging. In this study, we examined the protein levels of cPLA 2 and COX-2 enzymes in hippocampus, frontal pole and cerebellum from young (2-5 year-old), middle-aged (8-11 year-old) and old (23 year-old) male and female Rhesus monkeys. In the cerebellum, cPLA 2 protein level was higher in the young brain as compared to levels seen at both middle-aged and old. Similarly, in the frontal pole, the young brain showed a higher level of COX-2 protein as compared to the levels seen at both older ages. For both, once an animal reached 8-11 years of age the levels appeared to remain relatively constant over the next decade. Immunohistochemistry of COX-2 protein within the brain demonstrated no significant change in the localization to neurons within the frontal pole. In the young brain, the distribution of a low level of COX-2 protein within numerous neurons was different than the decreased number of neurons stained at a greater intensity in the adult brain. Based on the previous reports of localization of cPLA 2 and COX-2 at post-synaptic sites in neurons results from the current study suggest that the elevated protein levels of the two enzymes seen in the younger brain is related to the greater potential for synaptic plasticity across multiple neurons as a function of age and that cPLA 2 and COX-2 may be considered as post-synaptic markers.

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Section: Discussionsupporting

confidence: 93%

Regional protein levels of cytosolic phospholipase A2 and cyclooxygenase-2 in Rhesus monkey brain as a function of age

Weerasinghe

Coon

Bhattacharjee

et al. 2006

Brain Research Bulletin

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“…In this study, significant increases in the levels of mRNA for GFAP were found in the hippocampus, frontal (Brodmann's areas 9 and 10) and temporal cortex (areas 21, 22, and 38) in older (60-79 years) subjects as compared to younger (25-59 years) subjects. The protein levels of GFAP were also significantly correlated with age in frontal cortex (areas 9 and 44) and hippocampus in another cohort of human subjects (David et al, 1997). However, in another study a similar correlation was not found in non-neuropsychiatric control subjects in several brain regions including entorhinal cortex, midfrontal cortex, and orbital frontal cortex (Arnold et al, 1996).…”

Section: Discussionmentioning

confidence: 83%

Age-Dependent Reductions in the Level of Glial Fibrillary Acidic Protein in the Prefrontal Cortex in Major Depression

Miguel-Hidalgo

O'Dwyer

et al. 2004

Neuropsychopharmacol

233

125

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The density of glial cells is reduced in certain layers of the dorsolateral prefrontal cortex in major depressive disorder (MDD). Moreover, there are reductions in the packing density of glial fibrillary acidic protein (GFAP) immunoreactive astrocytes in the same cortical layers in younger subjects with MDD. The objective of the present study was to test if the level of GFAP is preferentially decreased in younger subjects with MDD, and whether GFAP levels are correlated with the age of onset of depression. Post-mortem brain tissue punches from dorsolateral prefrontal cortex were collected from 15 subjects with MDD and 15 age-matched psychiatrically normal control subjects. Western blots were performed on gels containing duplicated samples from both subjects of each matched pair, and on gels containing samples at different ages from either the MDD or the control group. The GFAP level was calculated as the ratio of the optical density of GFAP bands to actin bands in subjects with MDD and nonpsychiatric controls. Levels of GFAP were significantly lower in subjects with MDD as compared to controls and this decrease was most prominent in subjects less than 60 years old at the time of death. In the MDD group, GFAP levels were positively correlated with age at the time of death and show a trend toward correlation with the age of onset of depression. These findings indicate that a decrease in levels of GFAP may contribute to the pathophysiology of MDD, particularly in subjects of relatively young age.

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“…Indices of inflammation are known to be chronically elevated in the aged brain (David et al, 1997;Streit et al, 1999). In several age-related neurological diseases such as Alzheimer's disease, such inflammation is further increased (Mrak et al, 1995;Styren et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Inhaled ultrafine particulate matter affects CNS inflammatory processes and may act via MAP kinase signaling pathways

et al. 2008

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In addition to evidence that inhalation of ambient particulate matter (PM) can increase cardiopulmonary morbidity and mortality, the brain may also constitute a site adversely effected by the environmental presence of airborne particulate matter. We have examined the association between exposure to PM and adverse CNS effects in apolipoprotein E knockout (ApoE-/-) mice exposed to two levels of concentrated ultrafine particulate matter in central Los Angeles. Mice were killed 24 hr after the last exposure and brain, liver, heart, lung and spleen tissues were collected and frozen for subsequent bioassays. There was clear evidence of aberrant immune activation in the brains of exposed animals as judged by a dose-related increase in nuclear translocation of two key transcription factors, NF-kB and AP-1. These factors, are involved in the promotion of inflammation. Increased levels of glial fibrillary acidic protein (GFAP) were also found consequent to particulate inhalation suggesting that glial activation was taking place. In order to determine the mechanism by which these events occurred, levels of several MAP kinases involved in activation of these transcription factors were assayed by Western blotting. There were no significant changes in the proportion of active (phosphorylated) forms of ERK-1, IkB and p38. However the fraction of JNK in the active form was significantly increased in animals receiving the lower concentration of concentrated ambient particle (CAPs). This suggests that the signaling pathway by which these transcription factors are activated involves the activation of JNK.

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Glial reaction in the hippocampal formation is highly correlated with aging in human brain

Cited by 125 publications

References 15 publications

Regional protein levels of cytosolic phospholipase A2 and cyclooxygenase-2 in Rhesus monkey brain as a function of age

Regional protein levels of cytosolic phospholipase A2 and cyclooxygenase-2 in Rhesus monkey brain as a function of age

Age-Dependent Reductions in the Level of Glial Fibrillary Acidic Protein in the Prefrontal Cortex in Major Depression

Inhaled ultrafine particulate matter affects CNS inflammatory processes and may act via MAP kinase signaling pathways

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