CENTRAL AND PERIPHERAL EFFECT OF MPTP VIA DOSE-DEPENDENT MAGNESIUM MODULATION.

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 intake-dependent 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.

EXPERIMENTAL INDUCTION OF TYPE 2 DIABETES MELLITUS AND THE EFFICIENCY OF BARIATRIC SURGERY IN ITS REVERSAL IN RATS.

BACKGROUND: Following recent years, there is an increased body of literature on the connections that might exist between type 2 diabetes mellitus and the efficiency of bariatric surgery in its reversal compared to other medical approaches such as dieting. AIM: To induce experimentally type 2 diabetes mellitus in rats in order to observe the effects of bariatric surgery in the recovery as well as the reestablishment of normal insulin levels in order to extend the findings in house animals. MATERIALS AND METHODS: This study was conducted in three stages: the first consisted in inducing type 2 diabetes mellitus (T2DM) in 40 young Wistar male rats, by initially feeding them human food high in vegetal fats, oleaginous seeds, simple and complex carbohydrates, sugars, lipids, fats, proteins and fructose for a period of 8 weeks followed by a single low dose of streptozotocin (STZ), administered through intraperitoneal injection. The second stage of the study started when the rats became obese and therefore qualified for the bariatric procedure and the third stage consisted of post-operation supervision and care. The surgical procedure, performed on 10 obese rats, consisted in reducing the size of the stomach by partial gastrectomy of a 1.5 - 2.0 cm wide and 6.5 - 7.5 cm long area on the large curvature. RESULTS: Showed rapid improvements in body weight and blood sugar control after 9 days. CONCLUSION: After putting the rats on a diet high in carbohydrates, sugars, lipids and fats and administering them STZ, the induction of type 2 diabetes was successful and the partial gastrectomy led to a better blood sugar control. The bariatric procedure provides a faster therapeutic response than conventional diets.

Effects of serotonin depletion on behavior and neuronal oxidative stress status in rat: relevance for anxiety and affective disorders.

PURPOSE: We lesioned the hypothalamic paraventricular nucleus (PVN) of male Wistar rats using two different doses (8µg/3µl and 16µg/3µl) of 5,7-dihydroxytryptamine (5,7-DHT) and then animals were subjected to a battery of behavioral tests designed to assess anxiety and memory formation. Further, we were interested to know whether this lesion would result in neuronal oxidative stress and also if there is a correlation between the behavioral response to this lesion and brain oxidative stress. MATERIAL/METHODS: Behavioral tests included elevated plus maze, used to assess exploration/anxiety status and radial armmaze, used for determining spatial short-term and reference memory errors. Regarding the oxidative stress, we measured the extent of some lipid peroxidation products like malondialdehyde and defense enzymes such as superoxide dismutase and glutathione peroxidase. RESULTS: 5,7-DHT lesioned rats spent more time in the open arms of the elevated maze compared to sham-operated rats, suggesting that the lesion significantly diminished anxiety-like behavior. Also, short-term memory was significantly impaired, as shown by the working memory errors in radial arm-maze task. Further analyses revealed that the 5,7-DHT lesion did not result in a significant change of reference memory errors. Regarding the oxidative stress, no significant modification of both superoxide dismutase and glutathione peroxidase specific activities from the temporal lobe were observed. However, the malondiadehyde level was significantly increased, suggesting pro-oxidant effects. Also, the linear regression between the working memory errors vs. malondiadehyde resulted in significant correlations. CONCLUSION: 5,7 DHT lesion of the PVN affects behavioral performance via interactions with systems governing novel and/or fear-evoking situations and also by increasing neuronal oxidative stress.

[The effects of some cholinergic drugs on cognitive processes and oxidative stress in rat]. / Efectele unor diversi agenti colinergici asupra proceselor cognitive si stresului oxidativ la sobolan.

Reactive oxygen species (ROS) are produced within the body during oxygen metabolism and living organisms have developed several defense mechanisms to protect themselves from oxidative stress. Under normal conditions, ROS and antioxidant systems are in balance. Oxidative stress is caused by the imbalance between production of pro-oxidants and the antioxidant defenses. The defense mechanisms include antioxidant enzymes like superoxide dismutase (SOD) or glutathione peroxidase (GPX) and several no enzymatic free radical scavengers. It has been proposed that the progressive increase in ROS and consequent oxidative damage play the major role in neurodegenerative disorders. Learning and memory show an age-related decline and this age-associated impairment extends to spatial memory tasks. Furthermore, the neural circuits between the prefrontal cortex and striatum are also involved in spatial memory. In our previous studies, we have shown the facilitatory role of nicotine and cholinergic system in learning and memory processes. In the present study, we examined whether oxidative stress contributes to the memory deficits induced by muscarinic acetylcholine receptors (mAchRS) blocked by scopolamine. We also examined the effect of nicotine on oxidative stress, and also if nicotine could attenuated the learning and memory deficits induced by blocked of mAchRS. We observed that the levels of SOD and GPX decrease in rats mAchRS blockade by scopolamine (0.75 mg/kg body weight i.p.), and the level of malondialdehyde (MDA) increase in same rats, compared with saline-treated rats. Therefore, our results suggest that the oxidative stress contributes to the learning and memory deficits in rats.

The interaction between the cholinergic and dopaminergic system in learning and memory process in rats.

In normal rats, muscarinic acetylcholine receptors (mAChRs) have a facilitating role on both short-term and long-term memory tested by Y-maze task and multi-trial passive avoidance test, respectively, since scopolamine, a specific mAChRs antagonist, impairs both types of memory. A low dose of nicotine (0.3 mg/kg b.w., i.p.), a specific nicotinic acetylcholine receptors (nAChRs) agonist, administered once caused a significant facilitating effect on short-term memory. A higher dose of nicotine (3 mg/kg b.w., i.p.) administered 5 consecutively days had about the same facilitating effect on short- and long-term memory without affecting information acquisition. In rats, having mAChRs and nAChRs blocked by means of scopolamine and chlorisondamine respectively, a low dose of nicotine administered once caused a significant improvement of long-term memory deficits without affecting significantly short-term memory. A higher dose of nicotine administered 5 consecutive days in rats with a double blockade of cholinergic receptors had the same ameliorating effect on long-term memory deficits as low dose. Our data suggest that the antiamnesic effect of nicotine can result from an action at nicotinic receptors subtypes not blocked by chlorisondamine or at nonnicotinic receptors.