Number Of GFAP-immunoreactive Astrocytes Research Articles

Treatment of male rats with finasteride, an inhibitor of 5alpha-reductase enzyme, induces long-lasting effects on depressive-like behavior, hippocampal neurogenesis, neuroinflammation and gut microbiota composition

Persistent alteration of plasma neuroactive steroid levels associated with major depression has been recently reported in men after the suspension of the treatment for androgenetic alopecia with finasteride, an inhibitor of the enzyme 5alpha-reductase. Observations in male rats confirmed persistent alterations in neuroactive steroid levels also in the brain. In the present study, we have ascertained possible effects on depressive-like behavior, neurogenesis, gliosis, neuroinflammation and gut microbiota in male rats after subchronic treatment for 20 days with finasteride and after one month of its withdrawal. At the end of treatment there was an increase in the number of pH3 immunoreactive cells in the subgranular zone of the dentate gyrus together with an increase in the mRNA levels of TNF-α in the hippocampus. By one month after the end of finasteride treatment, rats showed depressive-like behavior coupled with a decrease in the number of pH3 immunoreactive cells in the subgranular zone of the dentate gyrus, a decrease in granule cell density in the granule cell layer and an increase in the number of GFAP immunoreactive astrocytes in the dentate gyrus. Finally, alteration of gut microbiota (i.e., an increase in Bacteroidetes phylum and in Prevotellaceae family at the end of the treatment and a decrease in Ruminococcaceae family, Oscillospira and Lachnospira genus at the end of the withdrawal period) was detected.In conclusion, finasteride treatment in male rats has long term effects on depressive-like behavior, hippocampal neurogenesis and neuroinflammation and gut microbiota composition.

Alteration of Glial Fibrillary Acidic Proteins Immunoreactivity in Astrocytes of the Spinal Cord Diabetic Rats

Diabetes affects retinal and nervous glial cells, especially the astrocytes. A key indicator of this response is the alteration in the level of intermediate filament glial fibrillary acidic protein (GFAP) and number of GFAP-immunoreactive astrocytes. To date, no study has investigated the effect of diabetes on the distribution of GFAP-immunoreactive astrocytes in the spinal cord. Therefore, the present study investigated the effect of diabetes on the number of GFAP-immunoreactive astrocytes in the gray matter of the spinal cord of streptozotocin-induced diabetic Wistar rats. Animals were divided into six groups (n = 7); 6 weeks and 12 weeks diabetic duration groups and their respective age-matched normal control and sham control groups. Our results demonstrated a significant (P < 0.001) decrease in the number of GFAP-immunoreactive astrocytes in different areas of the spinal cord sections of the 6 weeks and 12 weeks long diabetic rats when compared with the spinal cord of normal and sham control groups of comparable age. The mean percentage in total number of GFAP-immunoreactive astrocytes in the whole gray matter areas of the spinal cord of the 6 and 12 weeks diabetic groups were approximately 28% and 41% less than control groups. Furthermore, the 12 weeks diabetic group showed a significant (P < 0.001) reduction in the number of GFAP-immunoreactive astrocytes when compared with the 6 weeks diabetic animals. These results suggest that the induction of diabetes is associated with a reduction in GFAP-positive astrocytes in the spinal cord, which may affect the functional support and role of astrocytic cells in the nervous tissue. This in turn may contribute to the pathological changes associated with diabetic state in the central nervous system.

GFAP Expression in Astrocytes of Suprachiasmatic Nucleus and Medial Preoptic Area are Differentially Affected by Malnutrition during Rat Brain Development

The aim of the present study was investigate, in young rats, the effects of malnutrition on astrocyte distribution of two hypothalamic regions, the circadian pacemaker suprachiasmatic nucleus (SCN) and the medial preoptic area (MPA). Control rats were born from mothers fed on commercial diet since gestation and malnourished rats from mothers fed on multideficient diet, from the beginning of gestation (GLA group) or from the onset of lactation (LA group). After weaning, pups received ad libitum the same diet as their mothers, and were maintained under a 12/12 h light/dark cycle. The animals were analyzed either at 30-33, or 60-63 days of life. Brain coronal sections (50 μm) were processed to visualize glial fibrillary acidic protein (GFAP) immunoreactivity. Compared to control rats, both malnourished groups of 30 and 60 days exhibited a reduced number of GFAP-immunoreactive astrocytes in the SCN. The total GFAP-immunoreactive area in the SCN of the GLA group differed from the control group at both age ranges analyzed. The GFAP expression as measured by the relative optical density (ROD) exhibited a 50-60% reduction in the MPA in both malnourished groups, compared to controls. The results suggest that malnutrition early in life leads to alterations in gliogenesis or glial cell proliferation in both nuclei, being these alterations greater in the MPA. Compensatory plasticity mechanisms in the GFAP-expression seem to be developed in the astrocyte differentiation process in the SCN, especially when the malnutrition is installed from the lactation.

Estrogen receptor α-immunoreactive astrocytes are increased in the hippocampus in Alzheimer’s disease

Postmenopausal estrogen use may decrease the risk, and delay the onset and progression, of Alzheimer’s disease (AD). By means of fluorescence immunocytochemistry, the present study investigated the distribution of estrogen receptor α (ERα) in the human hippocampus in controls and in AD cases. ERα immunoreactivity was observed in neurons and glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes in the hippocampus both in controls and AD cases. The number and density of GFAP- and ERα-positive astrocytes was increased in AD. The number of GFAP-immunoreactive astrocytes, the number of nuclear ERα-staining astrocytes, and cytoplasmic ERα-staining astrocytes per unit area (1 mm 2) significantly increased ( P < 0.001, P < 0.05, P < 0.05, respectively) in CA1 in AD patients, while the percentage of ERα-immunoreactive astrocytes of the two groups did not differ ( P > 0.05). These data suggest an important role for ERα-mediated effects of estrogens on neurons and astrocytes in the hippocampus of human and AD patients.

Neurovirulent simian immunodeficiency virus induces calbindin-D-28K in astrocytes.

Astrocyte activation has been postulated to be a major contributor to functional changes in the brain of AIDS patients. We assessed astrocyte activation in the simian immunodeficiency virus (SIV) model. Four groups of macaque brains were examined: uninoculated controls, animals inoculated with virus that did not cause disease, animals inoculated with virus that caused AIDS but did not cause encephalitis, and animals with SIV encephalitis. We examined expression of calbindin-D-28K, a calcium binding protein that is upregulated in astrocytes during excitotoxic events, as well as glial fibrillary acidic protein (GFAP). The presence of calbindin in astrocytes was confirmed by double-labeling using confocal microscopy. Increases in calbindin staining were most apparent in the white matter, but increases in GFAP staining were most apparent in middle layers of the cerebral cortex. Six of the seven animals with SIV encephalitis had calbindin immunoreactive astrocytes in the subcortical white matter, corpus callosum, internal capsule, cerebral peduncle, pontine white matter, and cerebellar white matter. Very rarely, a few, very lightly calbindin-immunoreactive astrocytes were present in the uninoculated control brains. The increase in calbindin expression by astrocytes in SIV encephalitis suggests that these cells are subject to calcium toxicity. In uninoculated control macaques, and in macaques inoculated with virus that did not cause disease, GFAP-immunoreactive astrocytes were present throughout the subcortical white matter and in layer I, but very few were found in layers III-V of the cerebral cortex. Two animals that died of AIDS without encephalitis had somewhat higher numbers of GFAP immunoreactive astrocytes in middle cortical layers. In seven animals that received passaged neurovirulent virus and developed both AIDS and encephalitis, the number of GFAP-immunoreactive astrocytes in middle cortical layers was high, indicating widespread astrocyte activation.

Beta amyloid is neurotoxic in hippocampal slice cultures

We examined the neurotoxicity of the 40 amino acid fragment of beta amyloid peptide (Aβ1–40) in cultured hippocampal slices. When injected into area CA3, Aβ1–40 produced widespread neuronal damage. Injection of the reverse sequence peptide, Aβ40-1, or vehicle alone produced little damage. The distribution Aβ1–40 was highly correlated with the area of neuronal damage. Thioflavine S and electron microscopic analysis confirmed that injected Aβ1–40 formed 7–9 nm AD type amyloid fibrils in the cultures. Aβ1–40 also altered the number of GFAP immunoreactive astrocytes and ED-1 immunoreactive microglia/macrophages within and around the Aβ1–40 deposit. The observed neurotoxicity of Aβ1–40 in hippocampal slice cultures provides evidence that this peptide may be responsible for the neurodegeneration observed in AD.

Gonadal hormones down-regulate reactive gliosis and astrocyte proliferation after a penetrating brain injury

Astrocytes are a target for gonadal steroids in the normal brain. The putative modulation by gonadal hormones of the astrocytic reaction to brain injury was assessed in this study. Male and female adult Wistar albino rats were gonadectomized and, one month later, their brains were lesioned by a longitudinal incision crossing the parietal cerebral cortex, the CA1 field of the dorsal hippocampus and the dentate gyrus. Males were injected either with testosterone (20 μg/rat) or vehicle immediately after surgery. Females were injected either with 17β estradiol (250 μg/rat), progesterone (500 μg/rat) or vehicle. Hormonal injections were repeated 24 and 48 h after brain injury. All animals received injections of 5′-bromodeoxyuridine (BrdU) to label proliferating cells. Histological sections from the brain of animals killed 72 h after surgery were used for the double immunohistochemical localization of BrdU and glial fibrillary acidic protein (GFAP). The number of GFAP-immunoreactive astrocytes and the number of double labelled astrocytes (GFAP+BrdU) were recorded as a function of the distance to the lesion site in the parietal cerebral cortex, the CA1 field of the hippocampus and the dentate gyrus. Testosterone, estradiol and progesterone treatments resulted in a significant decrease in the number of GFAP-immunolabelled reactive astrocytes in the vicinity of the wound. The number of double labelled cells and the labelling index (proportion of GFAP-immunoreactive astrocytes labelled with BrdU) varied according to the cerebral area, the distance to the wound and the sex of the animals, and were significantly decreased by gonadal steroids in all the areas examined. These results ndicate that gonadal hormones may decrease gliosis and astrocyte proliferation after a penetrating brain injury.