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MK‐801 and ketamine induce heat shock protein HSP72 in injured neurons in posterior cingulate and retrosplenial cortex
Author(s) -
Sharp Frank R.,
Jasper Pat,
Hall John,
Noble Linda,
Sagar Stephen M.
Publication year - 1991
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410300609
Subject(s) - retrosplenial cortex , neuroprotection , nmda receptor , ketamine , heat shock protein , neuroscience , glutamate receptor , posterior cingulate , immunocytochemistry , medicine , hippocampus , cortex (anatomy) , chemistry , pharmacology , anesthesia , biology , receptor , biochemistry , gene
MK‐801 and ketamine are noncompetitive N ‐methyl‐D‐aspartate (NMDA) receptor blockers that decrease brain injury in animal models of focal and global ischemia. Recent reports, however, suggested that MK‐801 itself can damage neurons. Here we show that MK‐801 (0.1 to 5.0 mg/kg) and ketamine (40 to 100 mg/kg) typically induce heat shock protein HSP72 mainly in layer 3 neurons of the posterior cingulate and retrosplenial cortex of the rat. These HSP72‐immunoreactive neurons contain abnormal cytoplasmic vacuoles visualized by electron microscopy. The HSP72 immunoreactivity is maximal at 24 hours with 1.0‐mg/kg doses of MK‐801 and disappears by 2 weeks. Based on these data, we propose: (1) MK‐801 and ketamine injure selected neurons, which express HSP72 in response to that injury. (2) Since HSP72 is induced for 1 to 2 weeks, the prolonged psychological side effects of MK‐801, ketamine, phencyclidine, and related drugs could be related to this injury. (3) The neuroprotective effect of MK‐801 is probably not related to HSP72 induction. (4) HSP72 immunocytochemistry is useful for studying nonlethal neuronal injury from a wide variety of brain insults.