Estradiol (E2) Enhances Neurite Outgrowth by Repressing Glial Fibrillary Acidic Protein Expression and Reorganizing Laminin

Abstract Neuronal remodeling in response to deafferenting lesions in the brain can be enhanced by estradiol (E2). Astrocytes are among the targets of E2 in complex interactions with neurons and may support or inhibit neuronal remodeling. In ovariectomized female rats given entorhinal cortex lesions, E2 replacement inhibited the increase of glial fibrillary acidic protein (GFAP) protein. To model the role of E2 in these complex processes, we used the “wounding-in-a-dish” of astrocyte-neuron cocultures. Low physiological E2 (1 pm) blocks the wound-induced increase of GFAP expression (transcription and protein) and enhances neurite outgrowth. The transcriptional responses to E2 during wounding are mediated by sequences in the 5′-upstream region of the rat GFAP promoter. Concurrently, E2 reorganized astrocytic laminin into extracellular fibrillar arrays, which others have shown support neurite outgrowth. The inhibition of GFAP expression by E2 in this model is consistent with in vivo findings that E2 enhanced recovery from deafferenting cortical lesions by increased neurite outgrowth in association with decreased GFAP expression. More generally, we hypothesize that physiological variations in E2 levels modulate neuronal plasticity through direct effects on GFAP transcription that, in turn, modify GFAP-containing intermediate filaments and reorganize astrocytic laminin.

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Maternal food restriction in rats of the F0 generation increases retroperitoneal fat, the number and size of adipocytes and induces periventricular astrogliosis in female F1 and male F2 generations

Reproduction Fertility and Development ◽

10.1071/rd15309 ◽

2017 ◽

Vol 29 (7) ◽

pp. 1340 ◽

Cited By ~ 2

Author(s):

A. O. Joaquim ◽

C. P. Coelho ◽

P. Dias Motta ◽

L. F. Felício ◽

E. F. Bondan ◽

...

Keyword(s):

Glial Fibrillary Acidic Protein ◽

Food Restriction ◽

Bodyweight Gain ◽

Male Offspring ◽

Acidic Protein ◽

Female Rats ◽

Juvenile Period ◽

Gfap Expression ◽

F2 Generation ◽

F1 Generation

The present study investigated whether male offspring (F2 generation) from female rats (F1 generation) whose mothers (F0 generation) were food restricted during gestation inherit a phenotypic transgenerational tendency towards being overweight and obese in the juvenile period, in the absence of food restriction in the F1/F2 generations. Dams of the F0 generation were 40% food restricted during pregnancy. Bodyweight, the number and size of larger and small hypodermal adipocytes (HAs), total retroperitoneal fat (RPF) weight and the expression of glial fibrillary acidic protein (GFAP) in periventricular hypothalamic astrocytes (PHAs), as determined by immunohistochemistry, were evaluated in both generations. In the female F1 generation, there was low bodyweight gain only during the juvenile period (30–65 days of age), a decrease in the size of small adipocytes, an increase in the number of small adipocytes, an increase in RPF weight and an increase in GFAP expression in PHAs at 90–95 days of age. In males of the F2 generation at 50 days of age, there was increased bodyweight and RPF weight, and a small number of adipocytes and GFAP expression in PHAs. These data indicate that the phenotypic transgenerational tendency towards being overweight and obese was observed in females (F1) from mothers (F0) that were prenatally food restricted was transmitted to their male offspring.

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Immunoreactivity for glial fibrillary acidic protein and P2 receptor expression on astrocytes in vivo

Drug Development Research ◽

10.1002/ddr.10216 ◽

2003 ◽

Vol 59 (1) ◽

pp. 175-189 ◽

Cited By ~ 8

Author(s):

Heike Franke ◽

Ute Krügel ◽

Jens Grosche ◽

Peter Illes

Keyword(s):

Glial Fibrillary Acidic Protein ◽

Receptor Expression ◽

Acidic Protein ◽

P2 Receptor

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Glial Fibrillary Acidic Protein (GFAP) in Oligodendrogliomas: A Reflection of Transient GFAP Expression by Immature Oligodendroglia

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100036623 ◽

1986 ◽

Vol 13 (4) ◽

pp. 307-311 ◽

Cited By ~ 20

Author(s):

V. Jagadha ◽

W.C. Halliday ◽

L.E. Becker

Keyword(s):

White Matter ◽

Glial Fibrillary Acidic Protein ◽

Tumor Cells ◽

Intermediate Filaments ◽

Intermediate Filament ◽

Immunohistochemical Staining ◽

Neuron Specific Enolase ◽

Acidic Protein ◽

Gfap Expression ◽

S 100

ABSTRACT:Fourteen pure oligodendrogliomas were studied by light- and electronmicroscopy and immunohistochemistry to examine glial fibrillary acidic protein (GFAP) positivity in the tumors. To compare the immunohistochemical staining patterns of neoplastic oligodendroglia and immature oligodendroglia, myelination glia in the white matter of eight normal brains from children under 6 months of age were studied. The tumors possessed light microscopic and ultrastructural features characteristic of oligodendrogliomas. Microtubules were found in the cytoplasm of nine tumors on electronmicroscopy. In one, intermediate filaments and microtubules were observed in occasional tumor cells with polygonal crystalline structures in the cytoplasm. Using the peroxidase-antiperoxidase technique, all specimens were stained for GFAP, vimentin, S-100 and neuron-specific enolase (NSE). In nine tumors, variable numbers of cells with an oligodendroglial morphology reacted positively for GFAP. All tumors were positive for S-100 and negative for vimentin and NSE. The myelination glia in the eight normal brains stained positively for GFAP but not for vimentin. Vimentin is expressed by developing, reactive and neoplastic astrocytes. Thus, GFAP positivity combined with vimentin negativity in both neoplastic and immature oligodendroglia suggests that GFAP positivity in oligodendrogliomas may reflect the transient expression of this intermediate filament by immature oligodendroglia.

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A distal region, hypersensitive to DNase I, plays a key role in regulating rabbit whey acidic protein gene expression

Biochemical Journal ◽

10.1042/bj3590557 ◽

2001 ◽

Vol 359 (3) ◽

pp. 557-565 ◽

Cited By ~ 5

Author(s):

Benjamin MILLOT ◽

Marie-Louise FONTAINE ◽

Dominique THEPOT ◽

Eve DEVINOY

Keyword(s):

Mammary Gland ◽

Sequence Similarity ◽

Distal Region ◽

Dnase I ◽

Whey Acidic Protein ◽

Acidic Protein ◽

Upstream Region ◽

Lactating Mammary Gland

The aim of the present study was to identify the functional domains of the upstream region of the rabbit whey acidic protein (WAP) gene, which has been used with considerable efficacy to target the expression of several foreign genes to the mammary gland. We have shown that this region exhibits three sites hypersensitive to DNase I digestion in the lactating mammary gland, and that all three sites harbour elements which can bind to Stat5 in vitro in bandshift assays. However, not all hypersensitive regions are detected at all stages from pregnancy to weaning, and the level of activated Stat5 detected in the rabbit mammary gland is low except during lactation. We have studied the role of the distal site, which is only detected during lactation, in further detail. It is located within a 849bp region that is required to induce a strong expression of the chloramphenicol acetyltransferase reporter gene in transfected mammary cells. Taken together, these results suggest that this region, centred around a Stat5-binding site and surrounded by a variable chromatin structure during the pregnancy–lactation cycle, may play a key role in regulating the expression of this gene in vivo. Furthermore, this distal region exhibits sequence similarity with a region located around 3kb upstream of the mouse WAP gene. The existence of such a distal region in the mouse WAP gene may explain the differences in expression between 4.1 and 2.1kb mouse WAP constructs.

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