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

Objective(s): Vitamin E may have beneficial effects on oxidative stress and Aβ-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. © 2020 Mashhad University of Medical Sciences. All rights reserved

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. © 2018, Universidad de la Frontera. All rights reserved

Taurine can decrease phosphorylated tau protein levels in alzheimer�s model rats� brains

Background Microtubule formation is a dynamic process and Tau proteins promote the assembly of tubulin monomers into microtubules. Hyperphosphorylation of some amino acids in tau proteins causes neuron starvation and finally cell death. Taurine is found in the brain and has neuroprotective effects. Objective Since the protective and therapeutic effects of Taurine on phosphorylated tau proteins level in the cerebellum and prefrontal cortex of rats induced by scopolamine have not been studied, we examined these effects. Method Adult male Wistar rats were randomly distributed into nine groups. For two weeks, Taurine-treated rats received different doses of Taurine (25, 50, and 100 mg/kg/ day) before or after scopolamine injection. The phosphorylated tau protein level in the cerebellum and prefrontal cortex was determined by the enzyme-linked immunosorbent assay (ELISA) technique. Result Pretreatment with three doses of Taurine significantly decreased the phosphorylated tau protein level that increased by scopolamine in the prefrontal cortex (p < 0.001), as well as the cerebellum (p < 0.001). Moreover, high-dose administration of Taurine (100 mg/kg/day) after scopolamine injection significantly decreased phosphorylated tau protein level in the cerebellum (p < 0.01), as well as the prefrontal cortex (p < 0.05). However, there was not any significant change in the level of phosphorylated tau protein after Taurine treatment (25 and 50 mg/kg/day) in the cerebellum and prefrontal cortex. Conclusion It can be concluded that Taurine could attenuate the increase in phosphorylated tau protein induced by scopolamine in the brain of rats and usage of Taurine as a pretreatment complement could be more useful in the protection of neurons. © 2021, Kathmandu University. All rights reserved

Effects of hCG on reduced numbers of hCG receptors in the prefrontal cortex and cerebellum of rat models of Alzheimer�s disease

Age-associated changes in the levels of luteinizing hormone and human chorionic gonadotropin (hCG) are potential risk factors for Alzheimer�s disease (AD); hCG concentration is related to the incidence of AD. The highest density of hCG receptors is in zones of the brain that are vulnerable to AD and streptozotocin (STZ) can decrease the density of this receptor. We investigated the effects of different doses of hCG on hCG receptor density in the prefrontal cortex and cerebellum in a rat model of STZ-induced AD. AD was induced by intracerebroventricular injection of 3 mg/kg STZ. The resulting AD rats were treated for 3 days with 50, 100 or 200 IU/200 μl hCG, or with saline as a control. Sections of prefrontal cortex and cerebellum were stained immunohistochemically and hCG receptor-immunoreactive (ir) neurons were counted. STZ injected into the lateral ventricles of rat brains reduced the density of hCG receptor-ir neurons in the prefrontal cortex and cerebellum. hCG administration resulted in a significant dose-dependent increase in the number of hCG receptor-ir neurons in the prefrontal cortex and cerebellum. The maximum increase in the number of receptors occurred following the 200 IU dose of hCG. Administration of hCG ameliorated the lowered density of hCG receptor-ir neurons in the cerebellum and prefrontal cortex in STZ-induced AD rats. © 2019, © 2019 The Biological Stain Commission

α2-Adrenoceptor-ir neurons’ density changes after single dose of clonidine and yohimbine administration in the hippocampus of male rat

Objective: Despite the important role of α2-adrenoceptors in pain modulation processes, the impact of administration of α2-adrenoceptor agonist and antagonist on the density of hippocampal α2-adrenoceptor-immunoreactive neurons has not been investigated. Therefore, we aimed to determine the effect of single doses of clonidine and yohimbine on the density of α2-adrenoceptor-immunoreactive neurons in rat hippocampus. Materials and Methods: Adult male Wistar rats received a single dose of clonidine (0.7 mg/kg) alone or 5 min after intraperitoneal (1 mg/kg) and/or intracerebroventricular (5 µg/kg) injection of yohimbine. After histological processing, neurons with α2-adrenoceptor immunoreactivity were identified and counted through immunohistochemical analysis of hippocampal regions. Results: Clonidine slightly increased the number of α2-adrenoceptor-immunoreactive neurons in the hippocampal subregions compared with the normal saline group. Intraperitoneal injection of yohimbine followed by injection of clonidine significantly increased the number of α2-adrenoceptor-immunoreactive neurons in subregions cornu ammonis 1 (CA1) and cornu ammonis 3 (CA3). Intracerebroventricular injection of yohimbine after injection of clonidine significantly reduced the number of α2-adrenoceptor-immunoreactive neurons in all hippocampal subregions. Conclusion: The present study demonstrates that intraperitoneal administration of α2-adrenoceptor agonist clonidine increases the density of α2-adrenoceptor-immunoreactive neurons in rat hippocampus, while intracerebroventricular injection of yohimbine decreases the density of these neurons. © 2017 Informa UK Limited, trading as Taylor & Francis Group

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. Copyright © 2016. Anatomy & Cell Biology

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. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature

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

Objective(s): Amyloid β 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 β 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 Aβ 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 β plaques and cytochrome c in the hippocampus, prefrontal cortex, and cerebellum were immunohistochemically stained. Results: Density of congophilic Aβ 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 Aβ 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 Aβ plaque formation and decrease cytochrome c-immunoreactive neuron density in the brain. © 2019, Mashhad University of Medical Sciences. All rights reserved

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. © 2021 De Gruyter. All rights reserved