Altered MT1 and MT2 melatonin receptors expression in the hippocampus of pilocarpine-induced epileptic rats.

Clinical and experimental findings show that melatonin may be used as an adjuvant to the treatment of epilepsy-related complications by alleviates sleep disturbances, circadian alterations and attenuates seizures alone or in combination with AEDs. In addition, it has been observed that there is a circadian component on seizures, which cause changes in circadian system and in melatonin production. Nevertheless, the dynamic changes of the melatoninergic system, especially with regard to its membrane receptors (MT1 and MT2) in the natural course of TLE remain largely unknown. The aim of this study was to evaluate the 24-hour profile of MT1 and MT2 mRNA and protein expression in the hippocampus of rats submitted to the pilocarpine-induced epilepsy model analyzing the influence of the circadian rhythm in the expression pattern during the acute, silent, and chronic phases. Melatonin receptor MT1 and MT2 mRNA expression levels were increased in the hippocampus of rats few hours after SE, with MT1 returning to normal levels and MT2 reducing during the silent phase. During the chronic phase, mRNA expression levels of both receptors return to levels close to control, however, presenting a different daily profile, showing that there is a circadian change during the chronic phase. Also, during the acute and silent phase it was possible to verify MT1 label only in CA2 hippocampal region with an increased expression only in the dark period of the acute phase. The MT2 receptor was present in all hippocampal regions, however, it was reduced in the acute phase and it was found in astrocytes. In chronic animals, there is a reduction in the presence of both receptors especially in regions where there is a typical damage derived from epilepsy. Therefore, we conclude that SE induced by pilocarpine is able to change melatonin receptor MT1 and MT2 protein and mRNA expression levels in the hippocampus of rats few hours after SE as well as in silent and chronic phases.

Epilepsy and exercise: An experimental study in female rats.

OBJECTIVE: Epilepsy is the most common neurological chronic condition worldwide, affecting about 2% of world population. Temporal lobe epilepsy (TLE) reaches 40% of all cases of this condition, and it is highly refractory to pharmacological treatment. Physical activity has been suggested as complementary therapy for epilepsy. However, there is no consistent information whether all these effects are plenty applicable to females, since clinical and experimental studies concerning physical exercise and epilepsy are largely performed in males. Females are worthy of special attention due to gender specific particularities such as hormonal cyclical rhythm and possible pregnancy. Therefore, this study aimed to investigate the impact of two types of exercise programs (Forced and Voluntary) in female Wistar rats submitted to temporal lobe epilepsy induced by pilocarpine. METHODS: Animals were divided into four groups: Control (healthy), Epilepsy, Epilepsy/Forced (exercise in a treadmill) and Epilepsy/Voluntary (free access to wheel). Behavioral and histological analyses were evaluated among groups. RESULTS: Voluntary exercise was able to reduce seizure frequency and anovulatory estrous cycle occurrence. Yet, both types of exercise attenuated the mossy fiber sprouting in dentate gyrus. CONCLUSION: Our results indicate that voluntary exercise exerts a positive effect on epilepsy in female gender. Further investigations are necessary to better elucidate mechanisms involved in these responses, since these effects do not act in the same manner in male and female rats.

Effects of different physical exercise programs on susceptibility to pilocarpine-induced seizures in female rats.

In epilepsy, the most common serious neurological disorder worldwide, several investigations in both humans and animals have shown the effectiveness of physical exercise programs as a complementary therapy. Among the benefits demonstrated, regular exercise can decrease the number of seizures as well as improve cardiovascular and psychological health in people with epilepsy. While many studies in animals have been performed to show the beneficial effects of exercise, they exclusively used male animals. However, females are also worthy of investigation because of their cyclical hormonal fluctuations and possible pregnancy. Considering the few animal studies concerning seizure susceptibility and exercise programs in females, this study aimed to verify whether exercise programs can interfere with seizure susceptibility induced by pilocarpine in adult female Wistar rats. Animals were randomly divided into three groups: control, forced, and voluntary (animals kept in a cage with a wheel). After the final exercise session, animals received a pilocarpine hydrochloride (350 mg/kg i.p.; Sigma) injection to induce seizures. To measure the intensity of pilocarpine-induced motor signs, we used a scale similar to that developed by Racine (1972) in the kindling model. During a 4-h period of observation, we recorded latency for first motor signs, latency for reaching SE, number of animals that developed SE, and intensity of pilocarpine-induced motor signs. No difference was observed among groups in latency for first motor signs and in the number of animals that developed SE. Although the voluntary group presented more intense motor signs, an increased latency for developing SE was observed compared with that in forced and control groups. Our behavioral results are not enough to explain physiological and molecular pathways, but there are mechanisms described in literature which may allow us to propose possible explanations. Voluntary exercise increased latency to SE development. Further investigation is necessary to elucidate the pathways involved in these results, while more studies should be performed regarding gender specific differences.

Melatonin treatment decreases c-fos expression in a headache model induced by capsaicin.

The aim of the present work was to analyze c-fos response within the trigeminal nucleus caudalis (TNC) of pinealectomized rats and animals that received intraperitoneal melatonin, after intracisternal infusion of capsaicin, used to induce intracranial trigeminovascular stimulation. Experimental groups consisted of animals that received vehicle solution (saline-ethanol-Tween 80, 8:1:1, diluted 1:50) only (VEI, n=5); animals that received capsaicin solution (200 nM) only (CAP, n=6); animals submitted to pinealectomy (PX, n=5); sham-operated animals (SH, n=5); animals submitted to pinealectomy followed by capsaicin stimulation (200 nM) after 15 days (PX + CAP, n=7); and animals that received capsaicin solution (200 nM) and intraperitoneal melatonin (10 mg/kg) (CAP + MEL, n=5). Control rats, receiving vehicle in the cisterna magna, showed a small number of c-fos-positive cells in the TNC (layer I/II) as well as the sham-operated and pinealectomized rats, when compared to animals stimulated by capsaicin. On the other hand, pinealectomized rats, which received capsaicin, presented the highest number of c-fos-positive cells. Animals receiving capsaicin and melatonin treatment had similar expression of the vehicle group. Our data provide experimental evidence to support the role of melatonin and pineal gland in the pathophysiology of neurovascular headaches.