Differential Expression of Hippocampal Genes under Heat Stress

Exertional heat injury represents a major risk for people working or exercising in hot environments. Currently, no pharmacological therapies are available and little is known about the molecular response to heat stress in the brain. This study examined changes in gene expression associated with hyperthermia in the hippocampus of pigs. Twelve pigs were kept at either 70 degrees F (control) or 90 degrees F (heat stressed) for 4, 8, 12 and 24 h. The heart rate, respiratory rate and body temperature of the pigs were monitored hourly. At 4, 8, 12 and 24 h, the hippocampus was excised from three pigs in each group and total RNA was obtained for use in differential display PCR. A total of 31 differentially expressed cDNAs were isolated. Differential expressions of eight genes were further confirmed by real-time PCR analysis. Only slight increases in the expression HSP70, HSP90 and HSP27 genes were reported after heat stress at all time points. After 12 h of heat stress, DNA polymerase e p12 gene expression was stimulated to 2.55-fold of control level while it was down-regulated after both 4 and 8 h of heat stress exposure. Two genes encoding proteasome 26S subunits, PSMD10 and PSMB9, were also induced after exposure to heat stress for 4, 8 and 12 h to 2-fold or more of control levels. After 24 h, only PSMD10 was still elevated significantly. The superoxid dismutase-1 gene was significantly inhibited after both 8 and 12 h of heat stress, 0.39 and 0.45 fold of control levels respectively. The sodium-channel voltage gated beta 1 subunit gene was inhibited after heat stress. This inhibition was only significant after 24 h. In conclusion, most of the hippocampal genes of which the expression is altered by heat stress are play a role in cellular protection versus hyperthermic insult and some of the altered genes may play a role in heat-related brain pathogenesis. A greater understanding of heat-induced molecular changes in the brain could facilitate development of effective therapeutical strategies for treatment of heat-related illness.