Kynurenines in cognitive functions: their possible role in depression

Depression can originate from changes in tryptophan availability, caused by activation of the kynurenine pathway (KP) as a result of inflammation. Alterations in the KP and the changing levels of its metabolites have recently been considered to be factors contributing to the pathogenesis of depression. The key molecular mediator which induces the conversion of tryptophan into kynurenine is indoleamine-2,3-dioxygenase. Following its activation, both the production of neurotoxic compounds and the diminished peripheral accessibility of tryptophan are regarded as essential steps in the pathophysiological processes. The aim of this review is to survey the role of the KP in depression and its relationships with cognitive functions

Endogenous neuroprotection in chronic neurodegenerative disorders: with particular regard to the kynurenines

Parkinson’s disease (PD) and Huntington’s disease (HD) are progressive chronic neurodegenerative disorders that are accompanied by a considerable impairment of the motor functions. PD may develop for familial or sporadic reasons, whereas HD is based on a definite genetic mutation. Nevertheless, the pathological processes involve oxidative stress and glutamate excitotoxicity in both cases. A number of metabolic routes are affected in these disorders. The decrease in antioxidant capacity and alterations in the kynurenine pathway, the main pathway of the tryptophan metabolism, are features that deserve particular interest, because the changes in levels of neuroactive kynurenine pathway compounds appear to be strongly related to the oxidative stress and glutamate excitotoxicity involved in the disease pathogenesis. Increase of the antioxidant capacity and pharmacological manipulation of the kynurenine pathway are therefore promising therapeutic targets in these devastating disorders

Development of a small-animal focal brain irradiation model to study radiation injury and radiation-injury modifiers

Abstract Purpose: Our aim was to establish an effective small-animal focal brain radiation model for research on brain injuries. Material and methods: Groups of up to six rats were exposed to a range of doses from 120-40 Gy, at 10 intervals of a 6 MeV electron beam. Open-field motor functions and water maze learning-memory tests were performed after the irradiation at two-week intervals. Morphological changes were detected through repeated magnetic resonance imaging (MRI) monthly and were compared with the histopathological findings to determine if they predicted late microscopic changes. Results: The development of necrosis proved to be dose-dependent. 120 Gy resulted in serious deterioration within 4 weeks in all rats. Localized necrosis in one hemisphere was detected 2 months after the irradiation with >/= 70 Gy, and 3 months after 40-60 Gy consistent for all animals. The Morris water maze (MWM) tests proved to be the most sensitive tool for the early detection of a brain functional impairment. MRI screening provided useful information on the development of radiation necrosis, which defined the time point for histological examinations. Conclusions: The described method permits accurate dose delivery to a definite part in one hemisphere of the brain for six rats at a time. Following complex examinations, a dose of 40 Gy and a follow-up time of 4 months are proposed for investigations on neuroradiation modifiers