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Transforming growth factor β1 differently modulates wild‐type and TgF344‐AD astrocyte cultures' function
Author(s) -
de Souza Débora Guerini,
da Rocha Andreia Silva,
Salles Giovanna Bortoluzzi,
Oliveira Ana Cristina Laydner Joly,
Limberger Christian,
Bellaver Bruna,
Ferreira Pamela C.L.,
Povala Guilherme,
Zimmer Eduardo R.,
Souza Diogo O.
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.044253
Subject(s) - astrocyte , paracrine signalling , autocrine signalling , glial fibrillary acidic protein , fetal bovine serum , transforming growth factor , glutamate receptor , growth factor , medicine , biology , endocrinology , chemistry , microbiology and biotechnology , biochemistry , cell , immunology , receptor , immunohistochemistry , central nervous system
Abstract Background Astrocytes are key players involved in several functional aspects of the brain. They manage extracellular neurotransmitters and ions, regulate blood flow and energy substrates. Additionally, they produce and release growth factors, with autocrine and paracrine reach. Recently, the beneficial effects of Transforming Growth Factor β1 (TGF‐β1) have been shown in some experimental models of neurodegenerative diseases. However, the effects of TGF‐β1 in experimental models of Alzheimer’s Disease (AD) are still a matter of debate and further mechanistic investigation is needed. Here, we used adult astrocyte cultures prepared for the first time from Fischer TgF344‐AD (TG) rats to verify whether exogenous TGF‐β1 would affect astrocyte function. Method Cortices of adult (4‐month‐old) Fischer wild‐type (WT) and TG rats were aseptically dissected and digested with trypsin and papain. Cells suspensions were plated in 24‐well plates and cultivated for 3 weeks in DMEM/F12 supplemented with 10‐20% fetal bovine serum (FBS). At confluence, cells were treated with TGF‐β1 10 ng/mL for 1, 4 or 24h in DMEM/F12 1% FBS. Glutamate uptake was measured by radioactive assay and cellular morphology was evaluated with glial fibrillary acidic protein (GFAP) antibody and with rhodamine‐phalloidin for actin staining. Result Astrocytes from WT and TG rats take up the same amount of glutamate in basal conditions. WT astrocytes, however, respond to TGF‐β1 treatment increasing the levels of glutamate uptake nearly two‐fold after been treated for 4 or 24h (p<0.05), while TG astrocytes are not affected. GFAP and actin staining of the astrocytes shows extensive expression of the glial marker in the cytoskeleton and typical morphology (Figure 1 ‐ representative of TG astrocytes). Conclusion TGF‐β1 enhanced glutamate uptake in WT but not in TG astrocytes. This may be related to an intrinsic lesser ability to fulfill neuroprotective roles and decreased plasticity presented by TG astrocytes. Impaired astrocyte function is thought to be a decisive component of AD and here we show preliminary data that suggests decreased capacity of TG astrocytes to respond to neuroprotective compounds such as TGF‐β1. Whether the decreased response to TGF‐β1 is contributing to neurodegeneration or it is a consequence of neurotoxic stimulus in TG cells remains to be determined.