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

2017 ◽  
Vol 29 (7) ◽  
pp. 1340 ◽  
Author(s):  
A. O. Joaquim ◽  
C. P. Coelho ◽  
P. Dias Motta ◽  
L. F. Felício ◽  
E. F. Bondan ◽  
...  

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.

Endocrinology ◽  
2002 ◽  
Vol 143 (2) ◽  
pp. 636-646 ◽  
Author(s):  
Irina Rozovsky ◽  
Min Wei ◽  
David J. Stone ◽  
Hadi Zanjani ◽  
Christopher P. Anderson ◽  
...  

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.


Author(s):  
V. Jagadha ◽  
W.C. Halliday ◽  
L.E. Becker

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.


2016 ◽  
Vol 35 (5) ◽  
pp. 543-557
Author(s):  
Vic Ciaravino ◽  
Dina Coronado ◽  
Cheryl Lanphear ◽  
Alan Hoberman ◽  
Sanjay Chanda

Tavaborole is a topical antifungal agent approved by the US Food and Drug Administration for the treatment of toenail onychomycosis. The effects of tavaborole on gestation, parturition (delivery, labor), offspring development, and survival during the perinatal and postnatal periods were assessed in mated female rats. Females (F0 generation) were administered single daily oral (gavage) doses of 15, 60, or 100 mg/kg/d from gestation day 6 through lactation day 20. The females were allowed to deliver naturally and rear their offspring until lactation day 21, at which time the F0 females were euthanized. One male and female from each litter were selected (F1 generation) and retained for assessments, including growth, neurobehavior, fertility, and their ability to produce an F2 generation. Reproductive and offspring parameters were determined for the F1 and F2 generations, as applicable. F1 females and F2 pups were euthanized on postnatal day 7. In the F0 females, decreased activity was observed in the 100 mg/kg/d dose group. Excess salivation was observed in the 60 and 100 mg/kg/d dose groups (slight to moderate), however, this finding was not considered adverse. There were no tavaborole-related effects on the growth, viability, development, neurobehavioral assessments, or reproductive performance of the F1 generation. Survivability and mean body weight of the F2 pups were unaffected. The no observed adverse effect level (NOAEL) for maternal toxicity (F0 generation) was 60 mg/kg/d, based on the decreased activity observed in the 100 mg/kg/d dose group. The NOAEL for the offspring effects was ≥100 mg/kg/d, based on the lack of test article-related changes.


2002 ◽  
Vol 58 (1) ◽  
pp. 67-75 ◽  
Author(s):  
Alberto A Rasia-Filho ◽  
Léder L Xavier ◽  
Paula dos Santos ◽  
Günther Gehlen ◽  
Matilde Achaval

1996 ◽  
Vol 133 (4) ◽  
pp. 853-863 ◽  
Author(s):  
M Galou ◽  
E Colucci-Guyon ◽  
D Ensergueix ◽  
J L Ridet ◽  
M Gimenez y Ribotta ◽  
...  

Glial fibrillary acidic protein (GFAP) is an intermediate filament protein expressed predominantly in astrocytes. The study of its expression in the astrocyte lineage during development and in reactive astrocytes has revealed an intricate relationship with the expression of vimentin, another intermediate filament protein widely expressed in embryonic development. these findings suggested that vimentin could be implicated in the organization of the GFAP network. To address this question, we have examined GFAP expression and network formation in the recently generated vimentin knockout (Vim-) mice. We show that the GFAP network is disrupted in astrocytes that normally coexpress vimentin and GFAP, e.g., those of the corpus callosum or the Bergmann glia of cerebellum. Furthermore, Western blot analysis of GFAP protein content in the cerebellum suggests that posttranslational mechanisms are implicated in the disturbance of GFAP network formation. The role of vimentin in this process was further suggested by transfection of Vim-cultured astrocytes with a vimentin cDNA, which resulted in the normal assembly of the GFAP network. Finally, we examined GFAP expression after stab wound-induced astrogliosis. We demonstrate that in Vim- mice, reactive astrocytes that normally express both GFAP and vimentin do not exhibit GFAP immunoreactivity, whereas those that normally express GFAP only retain GFAP immunoreactivity. Taken together, these results show that in astrocytes, where vimentin is normally expressed with GFAP fails to assemble into a filamentous network in the absence of vimentin. In these cells, therefore, vimentin appears necessary to stabilize GFAP filaments and consequently the network formation.


Author(s):  
O. Z. Yaremchuk ◽  
K. A. Posokhova ◽  
O. S. Tokarskyi

The study aims to investigate the infuence of L-arginine on the content of nitrite anions (NO2¯) and nitrate anions (NO3¯) and the content of glial fibrillary acidic protein (GFAP) in the cerebellum and cerebral hemispheres of BALB/c mice with antiphospholipid syndrome. The studies were performed on 30 female BALB/c mice. The experimental animals were divided into 3 groups: 1 – control (intact) animals; 2 – animals with experimental antiphospholipid syndrome (APS), 3 – animals with APS, which were injected with L-arginine at a dose of 25 mg/kg, intraperitoneally once a day, for 10 consecutive days after the development of APS. The increase in glial fibrillary acidic protein and stable metabolites of nitric oxide NO2¯ and NO3¯ in the cerebellum and cerebral hemispheres, relative to the control, was observed in APS-developed BALB/c mice. In case of injection of the precursor of NO synthesis, L-arginine, animals with APS were found to have a further significant increase in the content of NO2¯ and NO3¯ in the cerebellum and the cerebral hemispheres. The introduction of L-arginine did not cause significant changes in GFAP (total) in cerebral hemispheres. However, GFAP content (49-37 kDa) was decreasing. The cerebellum showed an increase in GFAP (total) and GFAP (49-37 kDa) content, compared to the performance of animals with APS. Therefore, the increase in the content of GFAP in the cerebellum and the cerebral hemispheres of BALB/c mice under APS indicates the development of reactive astrogliosis. The introduction of the precursor of NO synthesis, L-arginine, is accompanied by an increase in the content of stable metabolites of nitric oxide (NO2¯, NO3¯) and GFAP in the cerebellum of BALB/c mice, which can indirectly confirm the role of NO in regulating of GFAP expression in astrocytes under APS.


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