Systemic injection of kainic acid: Gliosis in olfactory and limbic brain regions quantified with ( sup 3 H)PK 11195 binding autoradiography

Journal Article · Sat Sep 01 04:00:00 EDT 1990 · Experimental Neurology; (USA)

DOI:https://doi.org/10.1016/S0014-4886(05)80024-X· OSTI ID:6217546

Altar, C A; Baudry, M ^[1]

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1. Genentech, Inc., South San Francisco, CA (USA)

Neurodegenerative diseases may result from excessive stimulation of excitatory amino acid receptors by endogenous ligands. Because neuronal degeneration is associated with glial proliferation and hypertrophy, the degenerative changes throughout rat brain following the systemic administration of kainic acid (12 mg/kg) were mapped with quantitative autoradiography of (3H)PK 11195. This radioligand binds to a mitochondrial benzodiazepine binding site (MBBS) on microglia and astrocytes. Analysis of eight horizontal and four coronal brain levels revealed up to 16-fold increases in (3H)PK 11195 binding from 1 to 5 weeks but not 1 day after kainate injection. Increases in (3H)PK 11195 binding were predominantly in ventral limbic brain regions and olfactory projections to neocortical areas, with the olfactory cortex greater than subiculum/CA1 greater than anterior olfactory nucleus, medial thalamic nucleus, and piriform cortex greater than cingulate cortex and rostral hippocampus greater than dentate gyrus, septum, and amygdala greater than entorhinal cortex and temporal cortex. Little or no enhancement of (3H)PK 11195 binding was observed in numerous regions including the caudate-putamen, substantia nigra, nucleus accumbens, olfactory tubercle, cerebellum, thalamic nuclei, choroid plexus, medulla, parietal or occipital cortex, or pons. A 2-fold greater extent of neurodegeneration was obtained in ventral portions of the olfactory bulb, entorhinal cortex, temporal cortex, and dentate gyrus compared with the dorsal portions of these structures. The pattern of increase in (3H)PK 11195 binding closely matched the patterns of neuronal degeneration reported following parenteral kainate injection. These findings strengthen the notion that quantitative autoradiography of (3H)PK 11195 is a valuable tool to quantify the extent of neuronal degeneration.

• OSTI ID: 6217546
• Journal Information: Experimental Neurology; (USA), Journal Name: Experimental Neurology; (USA) Vol. 109:3; ISSN EXNEA; ISSN 0014-4886
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
AMINES
AUTORADIOGRAPHY
AZOLES
BIOCHEMICAL REACTION KINETICS
BODY
BRAIN
CELL PROLIFERATION
CENTRAL NERVOUS SYSTEM
DISEASES
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
INJECTION
INTAKE
INTRAPERITONEAL INJECTION
KINETICS
LIGANDS
NERVOUS SYSTEM
NERVOUS SYSTEM DISEASES
OLFACTORY BULBS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PATHOGENESIS
PYRROLES
PYRROLIDINES
REACTION KINETICS
TRITIUM COMPOUNDS