April 27, 2006

Halina Baran and Berthold Kepplinger

Halina Baran, Ph.D.

Biochemical and pharmacological insight into epilepsy research: Neurodegeneration and Neuroprotection

Institute of Physiology, Department of Natural Sciences, Veterinary Medical University Vienna & Neurochemical Laboratory, Karl Landsteiner Institute for Pain Treatment and Neurorehabilitation, LKM Amstetten-Mauer, Austria

Kainic acid, a rigid analogue of glutamic acid isolated from the Japanese sea weed Digenea simplex, is a cytotoxic agent causing strong excitation of neurons of the mammalian central nervous systems. The behavioural alterations in the rats and the neurochemical, and histopathological changes in their brains after systemic kainic acid application show similarities to the behavioural, neurochemical and histopathological alterations observed in human temporal lobe epilepsy. Using neurochemical and pharmacological approaches the involvement of excitatory and inhibitory neurotransmitters in the epileptic brains of kainic acid-treated rats will be discussed.

Kynurenine metabolism and neurodegeneration

Kynurenine serves as a major intermediate in the oxidative metabolism of tryptophan leading to niacin formation. Because of significant neurotoxic or neuroprotective effect of kynurenine metabolites’ i.e. 3-hydroxykynurenine, quinolinic acid or kynurenic acid, in animals studies, alterations of their synthesis may contribute to the pathogenesis of neurodegenerative disorders of humans and animals. Kynurenic acid alterations under different pathological conditions will be presented and effects of kynurenic acid will be discussed.

Berthold Kepplinger, M.D.

Kynurenine metabolism – clinical significance in aging and neurodegenerative disorders

Department of Neurology, Neuropsychiatric Hospital LKM Amstetten-Mauer
Department of Neurology, General Hospital Amstetten, Amstetten
Karl Landsteiner Institute for Pain Treatment and Neurorehabilitation, LKM Amstetten-Mauer, Austria

Kynurenic acid (KYNA) is an endogenous metabolite in the kynurenine pathway of tryptophan degradation and is an antagonist at the glycine site of the N-methyl-D-aspartate as well as at the alpha-7 nicotinic cholinergic receptors. The assumption that an increase of KYNA levels in the central nervous system in elder human subjects may be involved in the memory and/or cognitive decline is supported by the increased KYNA metabolism in Alzheimer’s patients, in patients with subcortical sclerotic encephalopathy, and in patients infected with HIV-1 virus. Improvement of memory by drugs affecting/influencing KYNA formation will be discussed.