Heat shock protein expression in vulnerable cells of the rat hippocampus as an indicator of excitation-induced neuronal stress

Abstract

The inducible 72 kDa heat shock protein (HSP72) has been shown to be protective in non-neuronal cells and neurons in culture, but its function and the control of its expression in the CNS are poorly understood. Although HSP72 is induced in neurons in vivo by neurotoxic compounds that produce seizures and neuronal damage, it is unknown if its expression is a specific response to excitation per se or to "stressful" or potentially injurious excitation, or if it is a marker or mediator of irreversible injury. We have attempted to identify the nature of the stimulus for HSP72 expression by utilizing focal electrical stimulation that can either excite or destroy postsynaptic cells, depending on the duration of afferent stimulation. Previous studies have demonstrated that intermittent stimulation of the main hippocampal afferent pathway for 24 hr evokes synchronous discharges in dentate granule cells but does not injure them. However, the same stimulation irreversibly destroys three of the four cell populations innervated by the granule cells. The three vulnerable populations are the dentate hilar mossy cells, the somatostatin/neuropeptide Y (NPY)-immunoreactive hilar neurons, and the CA3c pyramidal cells. The fourth and relatively resistant population is the GABA-immunoreactive dentate basket cells. In this study, we have localized HSP72 expression immunocytochemically in the hippocampal dentate gyrus in response to nontoxic durations of potentially neurotoxic afferent stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Alterations in τ Immunostaining in the Rat Hippocampus following Transient Cerebral Ischemia

“…Induction of a 72-kD heat shock protein (HSP72) is a sensitive marker of a variety of cellular stresses including ischemia, heat shock, hypoglycemia, and seizures (Brown, 1990) but is not necessarily pre dictive of neuronal death (Sloviter and Lowenstein, 1992). The distribution of HSP72 immunostained neurons at 24-72 h postischemia is similar to those that displayed altered T immunostaining within the first 2 h. It is of interest that in rats, heat shock results in increased somal T immunostaining similar to that observed following ischemia, except that phosphorylation of T is increased post-heat shock (Papasozomenos and Su, 1991).…”

Dentate Granule Cell Neurogenesis Is Increased by Seizures and Contributes to Aberrant Network Reorganization in the Adult Rat Hippocampus

“…numerous effects of pilocarpine as potential stimuli for SGZ mitotic activity, we used perforant path stimulation to elicit focal hippocampal seizures in adult rats. With this method, the degree of cell injury can be controlled by altering the duration of stimulation (Sloviter, 1983;Sloviter and Lowenstein, 1992;Sloviter et al, 1996). Animals underwent 6 hr of continuous perforant path stimulation, a duration that results in little or no hilar or pyramidal neuron injury (Fig.…”

Methods to identify and characterize developmental neurotoxicity for human health risk assessment. III: pharmacokinetic and pharmacodynamic considerations.

“…Examination of biomarkers of effect following exposure of a laboratory animal to a neurotoxicant can be used to identify the lowest dose capable of eliciting the potential adverse effect and provide information on the mechanism of action of the toxicant. A number of biomarkers have been used to identify insult in the adult nervous system, including astrocyte expression of glial fibrillary acidic protein (GFAP), induction of stress proteins, increased density of apoptotic cells, increased neuronal degeneration, and alterations in receptor density or function throughout the brain (113,114) [for review, see Costa (115)]. The applicability of studies characterizing biomarkers of effect in the developing nervous system depends on a clear understanding of the differences between juvenile and adult brains and adequate documentation and validation studies.…”