Damage to nerve terminals, reactive
gliosis and somatic degeneration can result when pronounced
hyperthermia occurs during
amphetamine (AMPH) exposure. The effects of AMPH-
induced hyperthermia and damage on the relative
mRNA levels for several heat shock/stress
proteins (Hsp27, Hsp60, Hsp70 and Hsc70), as well as secretory vesicle associated cysteinestring
protein (Csp1) were determined in both the striatum and substantia nigra using
reverse transcriptase polymerase chain reaction (RT-PCR). These changes were compared to changes in Hsp
mRNA levels seen in primary rat cerebral astrocyte cultures after heat shock/stress. Striatal Hsp70
mRNA increased about 2-fold over control levels at 16 hr after AMPH-
induced hyperthermia, and was the only Hsp species to significantly increase in response to AMPH. Hsp70
mRNA levels returned to control within 14 days after AMPH. Two-fold increases in Hsp70
mRNA were also seen in primary cultures of rat cerebrum 24 hr after heat shock. In primary cultures and brain tissue, the increased Hsp70
mRNA levels were still more than 500-fold less than constitutive Hsc70
mRNA and 50-fold less than Hsp60 levels. Hsp27
mRNA was not present in the striatum, nigra and primary cell cultures. Thus, the expression of Hsp species
mRNA measured was very similar in brain tissue and primary cell cultures. Because only a modest induction of Hsp 70
mRNA occurred, the Hsp species evaluated may only play a minor role in AMPH neurotoxicity. However, further studies are necessary to determine whether large increases in Hsp70 are occurring in selected neurons or glia in the striatum. RT-PCR products for Csp1 were produced in total
RNA obtained from brain but not from cultured astrocytes, suggesting that the Csp1
mRNA measured by RT-PCR is of neuronal origin. Csp1
mRNA levels were acutely downregulated in neurons in the substantia nigra, possibly in response to damage, but not the striatum after AMPH exposure. A slight long-term upregulation at 4 months of Csp1
mRNA may occur in the striatum but not in nigra.