Two Distinct Hippocampal Astrocyte Morphotypes Reveal Subfield-Different Fate during Neurodegeneration Induced by Trimethyltin Intoxication

Abstract

Astrocytes comprise a heterogenic group of glial cells, which perform homeostatic functions in the central nervous system. These cells react to all kind of insults by changing the morphology and function that result in a transition from the quiescent to a reactive phenotype. Trimethyltin (TMT) intoxication, which reproduces pathological events in the hippocampus similar to those associated with seizures and cognitive decline, has been proven as a useful model for studying responses of the glial cells to neurodegeneration. In the present study, we have explored morphological varieties of astrocytes in the hippocampal subregions of ovariectomized female rats exposed to TMT. We have demonstrated an early loss of neurons in CA1 and DG subfields. Distinct morphotypes of protoplasmic astrocytes observed in CA1/CA3 and the hilus of control animals developed different responses to TMT intoxication, as assessed by GFAP-immunohistochemistry. In CA1 subregion, GFAP+ astrocytes preserved their domain organization and responded with typical hypertrophy, while the hilar GFAP+ astrocytes developed atrophy-like phenotype and increased expression of vimentin and nestin 7 days after the exposure. Both reactive and atrophied-like astrocytes expressed Kir4.1 in CA1/CA3 and the hilus of DG, respectively, indicating that these cells did not change their potential for normal activity at this time point of pathology. Together, the results demonstrate the persistence of two protoplasmic morphotypes of astrocytes, with distinct appearance, function, and fate after TMT-induced neurodegeneration, suggesting their pleiotropic roles in the hippocampal response to neurodegeneration. © 2019 IBRO