ACTA ENDOCRINOLOGICA (BUC)

Background. Recent studies suggested that MPTP could cause gastrointestinal motility deficits additionally to its nonconclusive and controverted effects on the CNS (behavior and brain oxidative stress) in rats. A possible interaction between MPTP typical impairments and magnesium modulatory potential was previously suggested, as magnesium role was described in neuroprotection, gastrointestinal function, and oxidative stress. Aim. To investigate the possible modulatory effect of several magnesium intake formulations (via drinking water) in MPTP neurotoxicity and functional gastrointestinal impairment induction. Materials and Methods. Adult male Wistar rats were subjected to 3-week magnesium intake-controlled diets (magnesium depleted food and magnesium enriched drinking water) previously to acute subcutaneous MPTP treatment (30 mg/ kg body weight). Gastrointestinal motility (one hour stool collection test), and behavioral patterns (Y maze task, elevated plus maze test, open field test, forced swim test) were evaluated. Followingly, brain and bowel samples were collected, and oxidative stress was evaluated (glutathione peroxidase activity, malondial-dehyde concentrations). Results. MPTP could lead to magnesium intakedependent constipation-like gastrointestinal motility impairments, anxiety- and depressive-like affective behavior changes, and mild pain tolerance defects. Also, we found similar brain and intestinal patterns in magnesium-dependent oxidative stress. Conclusion. While the MPTP effects in normal magnesium intake could be regarded as not fully relevant in rat models and limited to the current experimental conditions, the abnormalities observed in the affective behavior, gastrointestinal status, pain tolerance, peripheric and central oxidative status could be indicative of the extent of the systemic effects of MPTP that are not restricted to the CNS level, but also to gastro-intestinal system.

The stress response is mediated by the hypothalamo-pituitary-adrenal (HPA) system.\r\nActivity of the hypothalamic paraventricular nucleus (PVN) forms the basis of the HPAaxis.\r\nBehavioral and endocrine responsivity to threat and their ontogenetic changes may be\r\nmediated by PVN.\r\nMethods. 6-hydroxydopamine (6-OHDA) remains the most widely used substance in\r\nanimal models for inducing highly reproducible brain lesions. In our study, parvocellular neurons\r\nfrom the PVN of male Wistar rats were chemical lesioned by right-unilateral stereotaxic injection\r\nof two different doses of 6-OHDA (8μg/3μl and 16μg/3μl) and were subjected to a battery of\r\nbehavioral tests designed to assess spatial memory formation (radial arm-maze task) and anxiety\r\n(elevated plus maze). Further, we were interested in knowing whether a 6-OHDA lesion of the\r\nPVN would result in an imbalance in neuronal oxidative stress levels.\r\nResults. 6-OHDA-induced PVN lesions significantly increased the number of\r\nworking memory errors, suggesting effects on short-term memory, without affecting longterm\r\nmemory, explored by number of reference memory errors in radial arm-maze task. In\r\nelevated plus maze measuring anxiety, 6-OHDA significantly diminished anxiety-like\r\nbehavior in a dose-dependent manner. In addition, the neurotoxin induced a reduction in\r\nsuperoxide dismutase (SOD) and glutathione peroxidase (GPX) specific activities, while\r\nmalondialdehyde (MDA) level was found increased in the temporal lobe of rat brain, the\r\nmost vulnerable cortical area to oxidative stress effects.\r\nConclusion. Results suggest that 6-OHDA lesion of the PVN affects behavioral\r\nperformance via interactions with systems governing arousal level and possibly by\r\nincreasing neuronal oxidative stress.