GFAP mRNA increases with age in rat and human brain

Nichols, Nancy R.; Day, Jonathan; Laping, Nicholas J.; Johnson, Steven A.; Finch, Caleb E.

doi:10.1016/0197-4580(93)90100-p

Cited by 356 publications

(224 citation statements)

References 51 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 congruence with significantly higher amounts of GFAP in the prefrontal cortex in older people with depression, Davis et al (2002) reported an increase in areal fraction of GFAP immunoreactivity in cortical layer I of dlPFC in older depressed subjects and no changes in the remaining cortical layers as compared to older controls. It has also been demonstrated that the levels of mRNA for GFAP increase with age in the human brain (Nichols et al, 1993). 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.…”

Section: Discussionsupporting

confidence: 54%

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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“…A similar phenomenon is likely to occur in human subjects. Increasing age at death is associated with reductions in certain mRNAs (Nichols et al 1993;Harrison et al 1995;Castensson et al 2002;Table 3). No age-dependent differences in the yield of human polysomes have been found, however (Langstrom et al 1989).…”

Section: Issues In Case Matchingmentioning

confidence: 99%

Biochemical and molecular studies using human autopsy brain tissue

Hynd

Lewohl

Scott

et al. 2003

Journal of Neurochemistry

221

171

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The use of human brain tissue obtained at autopsy for neurochemical, pharmacological and physiological analyses is reviewed. RNA and protein samples have been found suitable for expression profiling by techniques that include RT-PCR, cDNA microarrays, western blotting, immunohistochemistry and proteomics. The rapid development of molecular biological techniques has increased the impetus for this work to be applied to studies of brain disease. It has been shown that most nucleic acids and proteins are reasonably stable postmortem. However, their abundance and integrity can exhibit marked intra-and intercase variability, making comparisons between case-groups difficult. Variability can reveal important functional and biochemical information. The correct interpretation of neurochemical data must take into account such factors as age, gender, ethnicity, medicative history, immediate ante-mortem status, agonal state and post-mortem and post-autopsy intervals. Here we consider issues associated with the sampling of DNA, RNA and proteins using human autopsy brain tissue in relation to various ante-and postmortem factors. We conclude that valid and practical measures of a variety of parameters may be made in human brain tissue, provided that specific factors are controlled.

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GFAP mRNA increases with age in rat and human brain

Cited by 356 publications

References 51 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

Biochemical and molecular studies using human autopsy brain tissue

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