Heat shock in cultured neurons and astrocytes: correlation of ultrastructure and heat shock protein synthesis

Abstract

Cultured cerebral cortical neurons and astrocytes were compared after a brief shock. Morphological findings were correlated with the synthesis of the 68 kD heat shock protein (HSP68). Heat shocked neurons demonstrated many severe morphological changes after exposure to temperatures of 43 degrees C for 15 min and 45 degrees C for 10 min. Nuclear membrane 'blebbing' with lysis of the membrane, chromatin clumping, and disappearance of the nucleolus were prominent after both conditions. Lysis of the cell membrane was noted in severely injured neurons; this was more prominent at the higher temperature. In addition, alterations to polyribosomes, Golgi apparatus, rough endoplasmic reticulum and mitochondria were noted in the cytoplasm of neurons after heat shock. In contrast, no significant changes were noted in either the nucleus or cytoplasm of heat shocked astrocytes. The severity of morphological changes in neurons directly correlated with the low level of induction of HSP68 in neurons. Neurons synthesized much less 68 kD heat shock protein than similarly heat shocked astrocytes. We conclude that cultured cerebral cortical neurons are more susceptible to injury after heat shock than heat resistant astrocytes and that one possible mechanism of injury is failure to synthesize adequate amounts of HSP68 after injury.

Small subclass of rat olfactory neurons with specific bulbar projections is reactive with monoclonal antibodies to the HSP70 heat shock protein

“…It may simply be more efficient to replace than to repair these neurons after injury. Lethally injured neurons fail to show stress protein responses in other systems as well (Vass et al, 1988;Gonzalez et al, 1989;Nishimura, 1991; also see Sharp et al, 1991). In this regard it is interesting that supporting cells, gliallike cells involved in odorant inactivation and detoxification (Dahl, 1988;Dahl and Hadley, 1991;Chen et al, 1992) and possibly regulation of mucus ionic composition (Getchell et al, 1988) and which have a very low proliferation rate (Graziadei and Monti Graziadei, 19781, show pronounced stress responses following ketamine administration while the ORNs do not (Carr and Farbman, 1993a).…”

Opposing Actions of Phosphatidylinositol 3‐Kinase and Glycogen Synthase Kinase‐3β in the Regulation of HSF‐1 Activity

“…In addition to elevated temperature, the heat shock response has been reported to be activated by such conditions as oxidative stress (Gomer et al, 1996;Jacquier-Sarlin and Polla, 1996) and osmotic stress (Caruccio et al, 1997), and by agents such as heavy metals (Sarge et al, 1993), alkylating agents (Liu et al, 1996), and protease (Rossi et al, 1998) and proteosome inhibitors (Bush et al, 1997;Kawazoe et al, 1998). As in many other cells, the heat shock response also is activated in cells of neuronal origin (Marini et al, 1990;Nishimura et al, 1991;Mathur et al, 1994;Marcuccilli et al, 1996;Brown and Rush, 1999), but little is known about the neuronal control of this signaling system. The heat shock response culminates in the production of heat shock proteins (HSPs), such as heat shock protein-70 (HSP-70), which chaperone misfolded or damaged proteins (for reviews, see Morimoto, 1998;Morano and Thiele, 1999).…”

JRK binds satellite III DNA and is necessary for the heat shock response

“…Moreover, the occurrence of seizures in the Jrk null mouse is consistent with the well‐established neuroprotective function of mouse Hsps. For example, neurones with reduced Hsp70 expression are sensitive to physiological stresses such as excitatory neurotransmitter toxicity and elevated temperatures caused by inflammation and fever (Nishimura et al, 1991). Hippocampal neurons are particularly sensitive to stress, which may be due to low Hsp70 expression (Abe et al, 1998; States et al, 1996).…”