BRAIN NEUROTOXICITY OF PENITREM-A - ELECTROPHYSIOLOGICAL, BEHAVIORAL AND HISTOPATHOLOGICAL STUDY

The neurotoxicity of Penitrem A (PA) in rats was assessed against neur ophysiological, behavioral and histopathological parameters. Animals w ere acutely given intracerebroventricular (22-45 mg) or intraperitonea l injections (0.5-1.5 mg/kg) of PA. A typical trembling syndrome assoc iated with PA was always noted. Depending on the dose administered, an imals may convulse and eventually die (1-1.5mg/kg). PA-induced transie nt alterations of the EEG involving an increase in the frequency and v oltage of electrical activity recorded from the cerebral cortex. Hippo campal activity was not modified and some pathologic activities may be recorded at the thalamus. Generally these EEG alterations disappeared at d3 after the injection and the animals progressively recovered. Ho wever in the Inost severe cases, neuromotor disturbances were maintain ed at d7 (rotarod test). Coronal sections of the brain at the striatal , thalamic, hippocampal and pens levels mainly revealed that PA was ab le to induce dose related injuries in the cerebellum with massive dege neration of Purkinje cells and a significant vacuolization within the molecular layer. The neurotoxic mechanism remains unclear. Action of t he mycotoxin on the cerebello-thalamo-cortical tract is discussed. (C) 1998 Elsevier Science Ltd. All rights reserved.