Heat shock genes, including members of the heat shock 70 gene family, are highly conserved and some members are induced in response to environmental or physiological stress. In the heat shock 70 family, the heat shock cognate (hsc70) gene is expressed at high constitutive levels in non-stressed brain and at higher levels in stressed brain in all species examined so far. Inducible members of the family (hsp70) are expressed at very low levels in non-stressed rodent brain, and transiently expressed at high levels following stress. In contrast, hsp70 is expressed at much higher levels in all human brains assayed, even in persons who died suddenly and unexpectedly, with no documented agonal stress. High levels of expression of hsp70 could be a characteristic of human brain. Alternatively, post mortem interval (PMI), and/or premortem stressors could each be affecting the expression of the hsp70 gene family in human brain. In PMI studies, hsc70 and hsp70 protein was found to be stable for at least 27 hours in human brain. Even when premortem stress was eliminated (fever, hypoxia, coma etc. found in medical records) the constitutive levels of hsp70 protein were still several fold higher in sudden death human brain than that seen in stressed rodent. These results strongly suggest that constitutive expression of hsp70 is indeed many fold higher in human than in rodent brain. The non-human primate brain has been well characterized and its growth and development parallels that seen in human brain. The use of the monkey model would eliminate the inherent problems of working with human tissue, post mortem interval (PMI) as well as premortem stresses. In non-human primate brain, hsc70 and hsp70 mRNA levels were similar to those in humans. As in humans, hsp70 protein was constitutively expressed at high levels, only several fold less than the levels of hsc70 protein. The high hsp70 expression could be primate specific or it could be related to life span.
