Apelin-13 protects against memory impairment and neuronal loss, Induced by Scopolamine in male rats.

The present study aimed to evaluate the effects of Apelin-13 on scopolamine-induced memory impairment in rats. Forty male rats were divided into five groups of eight. The control group received no intervention; the scopolamine group underwent stereotaxic surgery and received 3 mg/kg intraperitoneal scopolamine. The treatment groups additionally received 1.25, 2.5 and 5 µg apelin-13 in right lateral ventricles for 7 days. All rats (except the control group) were tested for the passive avoidance reaction, 24 h after the last drug injection. For histological analysis, hippocampal sections were stained with cresyl violet; synaptogenesis biochemical markers were determined by immunoblotting. Apelin-13 alleviated scopolamine-induced passive avoidance memory impairment and neuronal loss in the rats' hippocampus (P<0.001). The reduction observed in mean concentrations of hippocampal synaptic proteins (including neurexin1, neuroligin, and postsynaptic density protein 95) in scopolamine-treated animals was attenuated by apelin-13 treatment. The results demonstrated that apelin-13 can protect against passive avoidance memory deficiency, and neuronal loss, induced by scopolamine in male rats. Further experimental and clinical studies are required to confirm its therapeutic potential in neurodegenerative diseases.

6-OHDA mediated neurotoxicity in SH-SY5Y cellular model of Parkinson disease suppressed by pretreatment with hesperidin through activating L-type calcium channels.

OBJECTIVES: Parkinson's disease (PD) is a neurological condition with selective progressive degeneration of dopaminergic neurons. Routine therapies are symptomatic and palliative. Although, hesperidin (Hsd) is known for its neuroprotective effects, its exact cellular mechanism is still a mystery. Considering the important role of calcium (Ca2+) in cellular mechanisms of neurodegenerative diseases, the present study aimed to investigate the possible effects of Hsd on Ca2+ channels in cellular model of PD and the possible association between the selective vulnerability of neurons in cellular models of PD and expression of the physiological phenotype that changes Ca2+ homeostasis. METHODS: SH-SY5Y cell line was used in this study; cell damage was induced by 150 µM 6-OHDA and the cells' viability was examined using MTT assay. Intracellular calcium, reactive oxygen species (ROS) and mitochondrial membrane potential were determined by the fluorescence spectrophotometry method. The expressions of calcium channel receptors were determined by gel electrophoresis and immunoblotting. RESULTS: Loss of cell viability and mitochondrial membrane potential were confirmed in 6-OHDA treated cells. In addition, intracellular ROS and calcium levels, calcium channel receptors significantly increased in 6-OHDA-treated cells. Incubation of SH-SY5Y cells with hesperidin showed a protective effect, reduced the biochemical markers of cell damage/death, and balanced calcium hemostasis. CONCLUSIONS: Based on our findings, it seems that hesperidin could suppress the progression of the cellular model of PD via acting on intracellular calcium homeostasis. Further studies are needed to confirm the potential benefits of preventive and therapeutic effects of stabilizing cellular calcium homeostasis in neurodegenerative disease.

Vitamin E therapy prevents the accumulation of congophilic amyloid plaques and neurofibrillary tangles in the hippocampus in a rat model of Alzheimer's disease.

OBJECTIVES: Vitamin E may have beneficial effects on oxidative stress and Aß-associated reactive oxygen species production in Alzheimer's disease. But, the exact role of vitamin E as a treatment for Alzheimer's disease pathogenesis still needs to be studied. Hence, we examined the therapeutic effects of vitamin E on the density of congophilic amyloid plaques and neurofibrillary tangles in rats' hippocampi. MATERIALS AND METHODS: Wistar rats were randomly assigned to control (no drug treatment), sham scopolamine (3 mg/kg)+saline and Sham scopolamine+sesame oil groups, and three experimental groups that received scopolamine+vitamin E (25, 50, and 100 mg/kg/day) daily for 14 days after scopolamine injection. The rats' brains were collected immediately following transcardial perfusion and fixed in 4% paraformaldehyde. Pathological brain alterations were monitored through Congo red and bielschowsky silver staining. RESULTS: Scopolamine treatment led to a significant increase in the density of congophilic amyloid plaques and neurofibrillary tangles in the hippocampus. IP injection of vitamin E in three doses (25, 50, and 100 mg/kg/day) significantly reversed the scopolamine-induced increase of the congophilic amyloid plaque density and density of neurofibrillary tangles in the hippocampus. Although vitamin E (25 and 50 mg/kg/day) doses were also effective, but a 100 mg/kg/day dose of vitamin E was more effective in the reduction of congophilic amyloid plaque and neurofibrillary tangle density. CONCLUSION: Vitamin E could exert a therapeutic effect in the reduction of congophilic amyloid plaque and neurofibrillary tangle density in the hippocampus of scopolamine-treated rats and it is useful for Alzheimer's disease.

Human chorionic gonadotropin attenuates amyloid-ß plaques induced by streptozotocin in the rat brain by affecting cytochrome c-ir neuron density.

OBJECTIVES: Amyloid ß plaques, in Alzheimer's disease, are deposits in different areas of the brain such as prefrontal cortex, molecular layer of the cerebellum, and the hippocampal formation. Amyloid ß aggregates lead to the release of cytochrome c and finally neuronal cell death in brain tissue. hCG has critical roles in brain development, neuron differentiation, and function. Therefore, we investigated the effect of hCG on the density of the congophilic Aß plaque and cytochrome c-ir neurons in the hippocampus, prefrontal cortex, and cerebellum of Streptozotocin (STZ)-treated rats. MATERIALS AND METHODS: Alzheimer model in rats (except the control group) was induced by streptozotocin (3 mg/kg, Intracerebroventricularly (ICV)). Experimental group rats received streptozotocin and then different doses of hCG (50, 100, and 200 IU, intraperitoneally) for 3 days. 48 hr after last drug injection and after histological processing, the brain sections were stained by congo red for congophilic amyloid ß plaques and cytochrome c in the hippocampus, prefrontal cortex, and cerebellum were immunohistochemically stained. RESULTS: Density of congophilic Aß plaques and cytochrome c-immunoreactive neurons was significantly higher in ICV STZ treated rats than controls. Treatment with three doses of hCG significantly decreased the density of congophilic Aß plaques and cytochrome c-immunoreactive neurons in the rat hippocampus, prefrontal cortex, and cerebellum in ICV STZ-treated rats (P<0.05). CONCLUSION: hCG can be useful in AD patients to prevent the congophilic Aß plaque formation and decrease cytochrome c-immunoreactive neuron density in the brain.

The protective effects of Citrus aurantium flower extract against 6-hydroxydopamine-mediated cell damage in human neuroblastoma SH-SY5Y cells / Los efectos protectores del extracto de flor de Citrus aurantium contra el daño celular mediado por 6-hidroxidopamina en células humanas de neuroblastoma SH-SY5Y

Parkinson's disease (PD) is described as a neurological condition, resulting from continuous degeneration of dopaminergic neurons. Currently, most treatments for neurodegenerative diseases are palliative. In traditional Iranian medicine, Citrus aurantium flower extract is used to treat some neural diseases, such as sleep disorders and anxiety. The tendency towards the use of medicinal herbs for the treatment of diseases (eg, seizure) is growing. Accordingly, we evaluated the antioxidant effects of C. aurantium flowers and analyzed their protective effects against 6-hydroxydopamine (6-OHDA)-mediated oxidative stress. In this study, 150 mM of 6-OHDA was used to induce cellular damage. Also, MTT assay was performed to analyze cellular viability. Fluorescence spectrophotometry was performed to measure the intracellular reactive oxygen species (ROS) and calcium levels. Based on the findings, 6-OHDA could reduce cell viability. We also analyzed the effects of C. aurantium against neurotoxicity. The intracellular levels of ROS and calcium greatly improved in cells exposed to 6-OHDA. SH-SY5Y cell incubation with C. aurantium (400 and 600 mg/mL) induced protective effects and decreased the biochemical markers of cell apoptosis. According to the findings, C. aurantium showed protective effects against neurotoxicity, caused by 6-OHDA; these protective properties were accompanied by antiapoptotic features. According to the findings, it seems that hydromethanolic C. aurantium extract can be used to prevent seizures.

La enfermedad de Parkinson (EP) se describe como una afección neurológica que resulta de la degeneración continua de las neuronas dopaminérgicas. Actualmente, la mayoría de los tratamientos para las enfermedades neurodegenerativas son paliativos. En la medicina tradicional iraní, el extracto de flor de Citrus aurantium se usa para tratar algunas enfermedades neurológicas, como los trastornos del sueño y la ansiedad. La tendencia hacia el uso de las medicinas para el tratamiento de enfermedades (por ejemplo, convulsiones) está creciendo. Por consiguiente, el objetivo de este trabajo consistió en evaluar los efectos antioxidantes de las flores de C. aurantium y analizar sus efectos protectores contra el estrés oxidativo mediado por la 6- hidroxidopamina (6-OHDA). En este estudio, se usó 150 mM de 6-OHDA para inducir daño celular. Además, se realizó un ensayo de MTT para analizar la viabilidad celular. La espectrofotometría de fluorescencia se realizó para medir las especies reactivas de oxígeno (ROS) intracelulares y los niveles de calcio. En base a los hallazgos, 6-OHDA podría reducir la viabilidad celular. También analizamos los efectos de C. aurantium contra la neurotoxicidad. Los niveles intracelulares de ROS y calcio se expandieron a las células expuestas a 6-OHDA. La incubación de células SH-SY5Y con C. aurantium (400 y 600 mg / ml) indujo efectos protectores y disminuyó los marcadores bioquímicos de la apoptosis celular. De acuerdo con los hallazgos, C. aurantium mostró efectos protectores contra la neurotoxicidad, causada por 6-OHDA; estas propiedades protectoras fueron acompañadas por características antiapoptóticas. Según los hallazgos, parece que el extracto hidrometanólico de C. aurantium se puede usar para prevenir las convulsiones.

Hippocampal serotonin-2A receptor-immunoreactive neurons density increases after testosterone therapy in the gonadectomized male mice.

The change of steroid levels may also exert different modulatory effects on the number and class of serotonin receptors present in the plasma membrane. The effects of chronic treatment of testosterone for anxiety were examined and expression of 5-HT2A serotonergic receptor, neuron, astrocyte, and dark neuron density in the hippocampus of gonadectomized male mice was determined. Thirty-six adult male NMRI mice were randomly divided into six groups: intact-no testosterone treatment (No T), gonadectomy (GDX)-No T, GDX-Vehicle, GDX-6.25 mg/kg testosterone (T), GDX-12.5 mg/kg T, and GDX-25 mg/kg T. Anxiety-related behavior was evaluated using elevated plus maze apparatus. The animals were anesthetized after 48 hours after behavioral testing, and decapitated and micron slices were prepared for immunohistochemical as well as histopathological assessment. Subcutaneous injection of testosterone (25 mg/kg) may induce anxiogenic-like behavior in male mice. In addition, immunohistochemical data reveal reduced expression of 5-HT2A serotonergic receptor after gonadectomy in all areas of the hippocampus. However, treatment with testosterone could increase the mean number of dark neurons as well as immunoreactive neurons in CA1 and CA3 area, dose dependently. The density of 5-HT2A receptor-immunoreactive neurons may play a crucial role in the induction of anxiety like behavior. As reduction in such receptor expression have shown to significantly enhance anxiety behaviors. However, replacement of testosterone dose dependently enhances the number of 5-HT2A receptor-immunoreactive neurons and interestingly also reduced anxiety like behaviors.