Serotonin-1A receptor activation in the median raphe nucleus improves response learning-based strategy in 192IgG saporin-induced cognitive impairments.

Deficits in the translation between egocentric-allocentric strategies may become another diagnostic mark for neurodegenerative disorders, especially Alzheimer's disease. Regarding the specific regional distribution of serotonin-1A receptor in brain areas mediating allocentric (externally-centered) spatial navigation to the escape location, here we studied the effects of median raphe nucleus serotonin-1A autoreceptors stimulation, [8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT); 4 µg/0.5 µl saline], of a selective cholinergic denervation by intracerebroventricular administration of the 192IgG saporin (1µl/each ventricle), on male Wistar rats search strategies in a Morris maze during acquisition, and before probe sessions. Despite some evidence of spatial hippocampal dependent knowledge to those PBS/Saline animals, their performance dropped to chance levels on probe trial. Therefore, we considered two probabilities and first analyzed the ability of the rats to make better use of one or more strategies. We showed statistically significant increases in the distances associated with egocentric (body-centered) non-spatial strategies, random searching in particular, in 192IgG/8OH rats, which led to their improved performance. Second, considering to what extent a shift in search strategy use improves performance indicated that 8-OH-DPAT alone did not affect learning since it appeared the related performance was impaired over days. However, the strategy choices made by 192IgG/8OH rats increased performance by more than 12% compared to 192IgG/Saline rats, an effect reversed with pre-treatment by serotonin-1A receptor antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexane-carboxamide (WAY 100635). The results strongly suggest the potential role of serotonergic system, via the serotonin-1A receptors, in spatial navigation. We argue that the receptors are of interest as therapeutic targets that can be used against age-related cognitive decline.

Myristica Fragrans Houtt Extract Attenuates Neuronal Loss and Glial Activation in Pentylenetetrazol-Induced Kindling Model.

Inflammatory reactions are closely associated with the development and progression of epilepsy. It has been shown that inhibition of pro-inflammatory cytokines, which are released from activated astrocytes and microglia, are considered to be an effective therapeutic approach for the treatment of epileptic disorders. Regarding the anti-inflammatory effects of nutmeg (Myristica fragrans Houtt), the present study was designed to investigate whether the nutmeg ethanolic extract could exert anticonvulsant and inhibitory effects on glial activation in pentylenetetrazol (PTZ)-induced mice model of kindling. Ethanolic extract of nutmeg was administrated intraperitoneally (i.p.) 1 hour before PTZ injection or one week before PTZ as a separate group, to become fully-kindled. The chemical components of nutmeg extract were analyzed by gas chromatography mass spectrometry (GC-MS). Immunostaining against neuronal and glial markers was performed on hippocampus sections. GC-MS data indicated that the main components of nutmeg extract are myristic acid (39.93%), elemicin (22.16%) and myristicin (11.17%). Behavioral studies showed that pre-treatment of nutmeg extract effectively reduced seizures behavior, decreased cell death, and ameliorated glial activation that is followed by PTZ administration. In conclusion, nutmeg extract might be regarded as a useful supplementary agent in epilepsy treatment through its attenuation of neuronal loss and glial activation.

Protective effect of raisin (currant) against spatial memory impairment and oxidative stress in Alzheimer disease model.

Objectives: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive pathological changes of the brain. A number of studies demonstrated compelling evidence of the importance of oxidative processes in AD pathogenesis. Raisin contains polyphenol, phenolic acid, and tannin compounds, which have antioxidant and anti-inflammatory properties. The present study was aimed to evaluate the protective effect of raisin on neurobehavioral and histological changes in rats with Alzheimer. Methods: Animal model of AD was induced by intraperitoneal injection of aluminium chloride for 60 days (100 mg/kg body weight). During these 60 days both Alzheimer's and control rats were given 6 g of raisin per rat. At the end of the treatment, blood was collected for biochemical assessment. We used a Morris water task and passive avoidance test to assess spatial memory. Results: Our results showed that aluminium exposure significantly decreased the memory in the MWT and passive avoidance test, but in the raisin + AlCl3 group, it significantly increased spatial memory in both tests. Also, Aluminium exposure significantly increased malondialdehyde (MDA) and decreased ferric reducing ability of plasma (ferric reducing/antioxidant power (FRAP)), while treatment with raisin significantly decreased MDA and increased FRAP in plasma of blood. Discussion: Our findings showed that raisin has a neuroprotective effect and improves the spatial memory in AD animal models.

Spatial Memory and Antioxidant Protective Effects of Raisin (Currant) in Aged Rats.

Diets rich in fruits and vegetables can prevent age-related diseases. This research was conducted to evaluate the effects of raisin consumption on the spatial memory and morphometric parameters of brain tissue in aging rats. Old rats (20 months of age) were divided into 2 groups: control and raisin, with 6 rats in each group. The raisin group received 6 g of raisins daily in addition to their food and water for 90 days. After treatments, all animals were evaluated by behavioral tests to assess spatial memory and learning alongside other tests including the ferric reducing antioxidant power (FRAP), malondialdehyde, and histological examinations. The results showed that there are significant differences in the Morris water task and passive avoidance learning of behavioral tests and biochemical tests (FRAP and thiobarbituric acid reactive substances) between the two groups. The histological study indicated that the cell count of the hippocampus, the diameter of the lateral ventricle, and area of the corpus callosum in the raisin group changed in comparison with the control group but they were not significant. The results demonstrated that raisins significantly raise antioxidant levels in blood and promotes cognitive and motor performance in aging rats.

Pregabalin enhances myelin repair and attenuates glial activation in lysolecithin-induced demyelination model of rat optic chiasm.

Multiple sclerosis (MS) is an autoimmune disease in which more than 70% of patients experience visual disturbance as the earliest symptoms. Lysolecithin (LPC)-induced focal demyelination model has been developed to evaluate the effects of different therapies on myelin repair improvement. In this study, the effects of pregabalin administration on myelin repair and glial activation were investigated. Local demyelination was induced by administration of LPC (1%, 2µL) into the rat optic chiasm. Rats underwent daily injection of pregabalin (30mg/kg, i.p) or vehicle. Visual-evoked potentials (VEPs) recordings were performed for evaluating the function of optic pathway on days 3, 7, 14 and 28 post lesions. Myelin specific staining and immunostaining against GFAP and Iba1 were also carried out for assessment of myelination and glial activation respectively. Electrophysiological data indicated that pregabalin administration could significantly reduce the P1-N1 latency and increase the amplitude of VEPs waves compared to saline group. Luxol fast blue staining and immunostaining against PLP, as mature myelin marker, showed that myelin repair was improved in animals received pregabalin treatment. In addition, pregabalin effectively reduced the expression of GFAP and Iba1 as activated glial markers in optic chiasm. The present study indicates that pregabalin administration enhances myelin repair and ameliorates glial activation of optic chiasm following local injection of LPC.

Fingolimod enhances myelin repair of hippocampus in pentylenetetrazol-induced kindling model.

Recent evidence indicates that demyelination occurs in epilepsy patients and kindling animal models. Regarding the well-known literature on anti-inflammatory and myelin protective effects of fingolimod (FTY720) in multiple sclerosis patients and animal models, we hypostatized whether FTY720 administration could exert myelin protective effects in pentylenetetrazol (PTZ)-induced kindling model. To end this, animals received 0.3 or 1mg/kg dosage of FTY720, 1h before PTZ injections. In another approach, after achieving fully kindling stage, FTY720 was administrated i.p. once daily for 7 consecutive days. Treatment with FTY720 (especially lower dose) reduced the frequency of seizures and epileptiform discharges in both approaches. We found that FTY720 administration decreases cell death and glial activation in CA1 and CA3 regions of hippocampus. Myelin protection effect was shown by increasing myelin levels. Furthermore, post-treatment of FTY720 enhanced endogenous remyelination and the number of oligodendrocyte precursor cells in fully kindled animals. Together, these results demonstrate that FTY720 behind the anti-inflammatory and neuroprotection effects has beneficial role in myelin protection and remyelination enhancement in PTZ kindling model of seizure and it may be provide a new therapeutic option for demyelination associated with epilepsy.