These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: The 1993 Upjohn Award Lecture. Quinolinic acid induced brain neurotransmitter deficits: modulation by endogenous excitotoxin antagonists.
    Author: Jhamandas KH, Boegman RJ, Beninger RJ.
    Journal: Can J Physiol Pharmacol; 1994 Dec; 72(12):1473-82. PubMed ID: 7736338.
    Abstract:
    Excitotoxins constitute a group of agents that are capable of activating excitatory amino acid receptors and producing axonsparing neuronal lesions. Focal injections of the exogenous excitotoxins kainic acid and ibotenic acid result in depletion of neurotransmitter markers in neuronal cell bodies located in areas of injection or in terminal zones of their projections. The discovery of endogenous agents that behave as excitotoxins has generated interest in the idea that excitotoxicity may contribute to the neuronal degeneration associated with a number of neurological diseases (Alzheimer's disease, Huntington's disease, Parkinson's disease) which involve selective neurotransmitter deficits. Quinolinic acid (QUIN), a pyridine dicarboxylic acid and metabolite of tryptophan, which has been detected in the central nervous system (CNS), behaves as an excitotoxin. In the mammalian brain QUIN has been localized to glial and immune cells, and its content increases with age. The neuro-excitatory and neurotoxic actions of QUIN are mediated via the Mg(2+)-sensitive N-methyl-D-aspartate (NMDA) receptor. The toxicity of QUIN, like that of kainate, but not ibotenate, is dependent on the presence of an intact glutamate-aspartate afferent input to the target area. Focal injections of QUIN into the nucleus basalis magnocellularis (nbM), a major source of cholinergic innervation to diencephalic areas, produce sustained loss of cholinergic neuron markers in the neocortex and amygdala. The neurotoxic action of QUIN on nbM results in an impairment of performance on memory-related tasks. Cortical and amygdaloid projecting cholinergic neurons show differential sensitivity to QUIN and other excitotoxic agents. This factor may partly explain the reported discrepancy between mnemonic deficits and the loss of cholinergic markers in the cerebral cortex induced by intra-nbM injections of certain excitotoxins. Cortical muscarinic receptor function is not significantly influenced by QUIN injections into the nbM producing loss of cortical cholinergic neurons. In the striatum, focal QUIN injections have been found to largely replicate the neurotransmitter deficits prevailing in Huntington's disease, an inherited movement disorder. Intrastriatal QUIN produces a profound loss of the NADPH diaphorase staining neurons in the area of injection but relatively spares these in the adjacent transition zone. QUIN is also highly damaging to the striatopallidal enkephalinergic neurons. However, at doses that are neurotoxic to striatal neurons, QUIN and several other excitotoxins produce significant elevations in enkephalin levels both in the striatum and globus pallidus. This elevation reflects the presence of a plasticity in the striatal enkephalinergic neuron population. The metabolic pathway yielding QUIN produces a number of intermediates that act as excitotoxin antagonists.(ABSTRACT TRUNCATED AT 400 WORDS)
    [Abstract] [Full Text] [Related] [New Search]