Dataset Information

Microglial and Astrocytic Function in Physiological and Pathological Conditions: Estrogenic Modulation.

ABSTRACT: There are sexual differences in the onset, prevalence, and outcome of numerous neurological diseases. Thus, in Alzheimer's disease, multiple sclerosis, and major depression disorder, the incidence in women is higher than in men. In contrast, men are more likely to present other pathologies, such as amyotrophic lateral sclerosis, Parkinson's disease, and autism spectrum. Although the neurological contribution to these diseases has classically always been studied, the truth is that neurons are not the only cells to be affected, and there are other cells, such as glial cells, that are also involved and could be key to understanding the development of these pathologies. Sexual differences exist not only in pathology but also in physiological processes, which shows how cells are differentially regulated in males and females. One of the reasons these sexual differences may occur could be due to the different action of sex hormones. Many studies have shown an increase in aromatase levels in the brain, which could indicate the main role of estrogens in modulating proinflammatory processes. This review will highlight data about sex differences in glial physiology and how estrogenic compounds, such as estradiol and tibolone, could be used as treatment in neurological diseases due to their anti-inflammatory effects and the ability to modulate glial cell functions.

SUBMITTER: Crespo-Castrillo A

PROVIDER: S-EPMC7247358 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Microglial and Astrocytic Function in Physiological and Pathological Conditions: Estrogenic Modulation.

Crespo-Castrillo Andrea A Arevalo Maria-Angeles MA

International journal of molecular sciences 20200502 9

There are sexual differences in the onset, prevalence, and outcome of numerous neurological diseases. Thus, in Alzheimer's disease, multiple sclerosis, and major depression disorder, the incidence in women is higher than in men. In contrast, men are more likely to present other pathologies, such as amyotrophic lateral sclerosis, Parkinson's disease, and autism spectrum. Although the neurological contribution to these diseases has classically always been studied, the truth is that neurons are not ...[more]

PMID: 32370112

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Project description:BACKGROUND:Brain pericytes ensheathe the endothelium and contribute to formation and maintenance of the blood-brain-barrier. Additionally, pericytes are involved in several aspects of the CNS immune response including scarring, adhesion molecule expression, chemokine secretion, and phagocytosis. In vitro cultures are routinely used to investigate these functions of brain pericytes, however, these are highly plastic cells and can display differing phenotypes and functional responses depending on their culture conditions. Here we sought to investigate how two commonly used culture media, high serum containing DMEM/F12 and low serum containing Pericyte Medium (ScienCell), altered the phenotype of human brain pericytes and neuroinflammatory responses. METHODS:Pericytes were isolated from adult human brain biopsy tissue and cultured in DMEM/F12 (D-pericytes) or Pericyte Medium (P-pericytes). Immunocytochemistry, qRT-PCR, and EdU incorporation were used to determine how this altered their basal phenotype, including the expression of pericyte markers, proliferation, and cell morphology. To determine whether culture media altered the inflammatory response in human brain pericytes, immunocytochemistry, qRT-PCR, cytometric bead arrays, and flow cytometry were used to investigate transcription factor induction, chemokine secretion, adhesion molecule expression, migration, phagocytosis, and response to inflammatory-related growth factors. RESULTS:P-pericytes displayed elevated proliferation and a distinct bipolar morphology compared to D-pericytes. Additionally, P-pericytes displayed lower expression of pericyte-associated markers NG2, PDGFR?, and fibronectin, with notably lower ?SMA, CD146, P4H and desmin, and higher Col-IV expression. Nuclear NF-kB translocation in response to IL-1? stimulation was observed in both cultures, however, P-pericytes displayed elevated expression of the transcription factor C/EBP?, and lower expression of the adhesion molecule ICAM-1. P-pericytes displayed elevated phagocytic and migratory ability. Both cultures responded similarly to stimulation by the growth factors TGF?1 and PDGF-BB. CONCLUSIONS:Despite differences in their phenotype and magnitude of response, both P-pericytes and D-pericytes responded similarly to all examined functions, indicating that the neuroinflammatory phenotype of these cells is robust to culture conditions.

Dataset Information

Microglial and Astrocytic Function in Physiological and Pathological Conditions: Estrogenic Modulation.

Publications

Microglial and Astrocytic Function in Physiological and Pathological Conditions: Estrogenic Modulation.

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