MK-801 and ketamine induce heat shock protein HSP72 in injured neurons in posterior cingulate and retrosplenial cortex. 1991

F R Sharp, and P Jasper, and J Hall, and L Noble, and S M Sagar
Department of Neurology, University of California, San Francisco.

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.

UI MeSH Term Description Entries
D007649 Ketamine A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE) and may interact with sigma receptors. 2-(2-Chlorophenyl)-2-(methylamino)cyclohexanone,CI-581,Calipsol,Calypsol,Kalipsol,Ketalar,Ketamine Hydrochloride,Ketanest,Ketaset,CI 581,CI581
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D005260 Female Females
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006179 Gyrus Cinguli One of the convolutions on the medial surface of the CEREBRAL HEMISPHERES. It surrounds the rostral part of the brain and CORPUS CALLOSUM and forms part of the LIMBIC SYSTEM. Anterior Cingulate Gyrus,Brodmann Area 23,Brodmann Area 24,Brodmann Area 26,Brodmann Area 29,Brodmann Area 30,Brodmann Area 31,Brodmann Area 32,Brodmann Area 33,Brodmann's Area 23,Brodmann's Area 24,Brodmann's Area 26,Brodmann's Area 29,Brodmann's Area 30,Brodmann's Area 31,Brodmann's Area 32,Brodmann's Area 33,Cingulate Gyrus,Gyrus Cinguli Anterior,Retrosplenial Complex,Retrosplenial Cortex,Anterior Cingulate,Anterior Cingulate Cortex,Cingular Gyrus,Cingulate Area,Cingulate Body,Cingulate Cortex,Cingulate Region,Gyrus, Cingulate,Posterior Cingulate,Posterior Cingulate Cortex,Posterior Cingulate Gyri,Posterior Cingulate Gyrus,Posterior Cingulate Region,Superior Mesial Regions,24, Brodmann Area,Anterior Cingulate Cortices,Anterior Cingulates,Anterior, Gyrus Cinguli,Anteriors, Gyrus Cinguli,Area 23, Brodmann,Area 23, Brodmann's,Area 24, Brodmann,Area 24, Brodmann's,Area 26, Brodmann,Area 26, Brodmann's,Area 29, Brodmann,Area 29, Brodmann's,Area 30, Brodmann,Area 30, Brodmann's,Area 31, Brodmann,Area 31, Brodmann's,Area 32, Brodmann,Area 32, Brodmann's,Area 33, Brodmann,Area 33, Brodmann's,Area, Cingulate,Body, Cingulate,Brodmanns Area 23,Brodmanns Area 24,Brodmanns Area 26,Brodmanns Area 29,Brodmanns Area 30,Brodmanns Area 31,Brodmanns Area 32,Brodmanns Area 33,Cingulate Areas,Cingulate Bodies,Cingulate Cortex, Anterior,Cingulate Cortex, Posterior,Cingulate Gyrus, Anterior,Cingulate Gyrus, Posterior,Cingulate Region, Posterior,Cingulate Regions,Cingulate, Anterior,Cingulate, Posterior,Cinguli Anterior, Gyrus,Cinguli Anteriors, Gyrus,Complex, Retrosplenial,Cortex, Anterior Cingulate,Cortex, Cingulate,Cortex, Posterior Cingulate,Cortex, Retrosplenial,Gyrus Cinguli Anteriors,Gyrus, Anterior Cingulate,Gyrus, Cingular,Gyrus, Posterior Cingulate,Posterior Cingulate Cortices,Posterior Cingulate Regions,Posterior Cingulates,Region, Cingulate,Region, Posterior Cingulate,Retrosplenial Complices,Retrosplenial Cortices,Superior Mesial Region
D006360 Heat-Shock Proteins Proteins which are synthesized in eukaryotic organisms and bacteria in response to hyperthermia and other environmental stresses. They increase thermal tolerance and perform functions essential to cell survival under these conditions. Stress Protein,Stress Proteins,Heat-Shock Protein,Heat Shock Protein,Heat Shock Proteins,Protein, Stress
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015415 Biomarkers Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, ENVIRONMENTAL EXPOSURE and its effects, disease diagnosis; METABOLIC PROCESSES; SUBSTANCE ABUSE; PREGNANCY; cell line development; EPIDEMIOLOGIC STUDIES; etc. Biochemical Markers,Biological Markers,Biomarker,Clinical Markers,Immunologic Markers,Laboratory Markers,Markers, Biochemical,Markers, Biological,Markers, Clinical,Markers, Immunologic,Markers, Laboratory,Markers, Serum,Markers, Surrogate,Markers, Viral,Serum Markers,Surrogate Markers,Viral Markers,Biochemical Marker,Biologic Marker,Biologic Markers,Clinical Marker,Immune Marker,Immune Markers,Immunologic Marker,Laboratory Marker,Marker, Biochemical,Marker, Biological,Marker, Clinical,Marker, Immunologic,Marker, Laboratory,Marker, Serum,Marker, Surrogate,Serum Marker,Surrogate End Point,Surrogate End Points,Surrogate Endpoint,Surrogate Endpoints,Surrogate Marker,Viral Marker,Biological Marker,End Point, Surrogate,End Points, Surrogate,Endpoint, Surrogate,Endpoints, Surrogate,Marker, Biologic,Marker, Immune,Marker, Viral,Markers, Biologic,Markers, Immune

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