Expression of heat shock transcription factor 1 and its downstream target protein T-cell death associated gene 51 in the spinal cord of a mouse model of amyotrophic lateral sclerosis

Abstract

Heat shock transcription factor 1 (HSF1) modulates the expression of the cell survival heat shock protein 70 (HSP70) and the cell death T-cell death associated gene 51 (TDAG51) in response to heat shock and various other cell stressors. We previously reported an increase in HSP70 in glial cells of the spinal anterior horn. Here we examined the temporal and spatial changes of HSF1 and TDAG51 expression over the course of motor neuron degeneration in the spinal cord of a mouse model of ALS (G93A-SOD1 Tg mice). The number of glial-like cells expressing HSF1 increased in G93A-SOD1 Tg mice at both early symptomatic (14 weeks) and end stages of disease (18 weeks), while the number of spinal neurons expressing HSF1 decreased. The total level of HSF1 in the anterior lumbar spinal cord was significantly decreased in G93A-SOD1 Tg mice at the end stage of disease. In contrast to HSF1, the level of TDAG51 in the anterior lumbar spinal cord was significantly increased in G93A-SOD1 Tg mice at the end stage of disease. Moreover, TDAG51 progressively increased in glial-like cells in the anterior lumbar spinal cord of G93A-SOD1 Tg mice from the early symptomatic stage, while decreasing in spinal neurons. Taken together, our results suggest that the balance between the cell survival and death signals mediated by HSP70 and TDAG51, respectively, may be disturbed by the altered expression of HSF1 during the progression of disease in this ALS model.