Enlarged ventricles, astrogliosis and neurodegeneration in heat shock factor 1 null mouse brain.

Heat shock transcription factors mediate the regulation of the organism physiological maintenance and adaptation. We investigated the morphology and cellular expression of selected genes in brains of transgenic mice lacking the heat shock transcription factor 1, HSF1, the main transactivator under stress conditions. All HSF1 null mice displayed major brain morphological alterations: the lateral ventricles were markedly enlarged and the white matter reduced, as in ventriculomegaly. Heterozygous mice for the HSF1 gene also had these abnormalities albeit to a lower extent in comparison to the wild type, indicating a gene dosage effect. Cell loss, vacuolisation, amorphous eosinophilic cytoplasm and pyknotic nucleus were evident in the white matter, especially in periventricular regions. These areas also exhibited astrogliosis and neurodegeneration. The expression of heat shock protein hsp 27 was up-regulated whereas alpha B-crystallin was down-regulated in different areas of HSF1 null mouse brain in comparison to control mice. These data implicate HSF1 in maintaining the postnatal mammalian brain under non-stress conditions.