IMMEDIATE-EARLY GENE-EXPRESSION IN THE BRAIN OF THE THIAMINE-DEFICIENT RAT

Pyrithiamine-induced thiamine deficiency (PTD) in the rat is associate d with neuronal loss in the thalamus and inferior colliculus. Recently , we were able to demonstrate the occurrence of apoptosis in the thala mus of these animals. Given that immediate-early genes (IEGs) particip ate in signal transduction pathways that mediate programmed cell death , the present study utilized in situ hybridization and immunohistochem istry to examine the expression of four IEGs (c-fos, c-jun, fos-B, and NGFI-A) during the progression of PTD. Elevated c-fos mRNA levels wer e initially observed in the posterior medial thalamus on d 12 of the d eficiency. At the acute symptomatic stage (characterized by a loss of righting reflex on d 16-17), the posterior-medial thalamus exhibited i ncreased mRNA for all genes examined, whereas the inferior colliculus demonstrated mRNA induction for c-fos, c-jun, and NGFI-A. Immunohistoc hemical analysis revealed that elevations of IEG mRNA associated with the acute symptomatic stage were consistently translated into protein in the thalamus. In contrast, whereas elevated Fos-and Jun-like immuno reactivity were detected in the inferior colliculus at this stage, NGF I-A-like immunoreactivity declined significantly below basal levels, s uggesting a translational block. These results are consistent with our recent findings of apoptotic cell death, and indicate that differenti al patterns of IEG expression occur in the thalamus and inferior colli culus during PTD, which may contribute to the pathogenesis of this dis order.