Papers by Mehrdad Jahanshahi
Journal of Clinical and Basic Research, 2023
Background: Neurodegenerative diseases (NDDs) cause progressive neuronal loss, resulting in morbi... more Background: Neurodegenerative diseases (NDDs) cause progressive neuronal loss, resulting in morbidity and mortality. Research is continued on treatment strategies that can tackle the disease's pathophysiology and cease its progression. Considering the anti-apoptotic and neuroprotective properties of apelin, we hypothesized that apelin-13 could be a therapeutic solution for Alzheimer's disease and similar NDDs. Therefore, we evaluated its effect on scopolamine-treated rats.
Methods: Male rats (n=40) were assigned to 5 groups of 8. No intervention was considered for the control group. The scopolamine group received stereotaxic surgery and was treated with 3 mg/kg scopolamine intraperitoneally. The treatment groups were treated with scopolamine plus intraventricular injection of apelin-13 (1.25, 2.5, and 5 µg) into the right lateral ventricles for 7 days. For evaluating the memory impairment, the passive avoidance reactions of the animals, except the control group, were assessed 24 hours following the last injection. Regarding histological analysis, Congo red staining of the hippocampal sections was done, and immunoblotting was used to determine apoptotic biochemical markers, including caspase 3, cytochrome C, and congophilic amyloid-beta plaques.
Results: Apelin–13 alleviated scopolamine-related passive avoidance memory impairment and reduced the number of congophilic amyloid-beta plaques in the hippocampus (all P<0.001). It attenuated the decrease in the mean levels of hippocampal apoptotic proteins (caspase 3, cytochrome C) in animals treated with scopolamine (all P<0.05).
Conclusion: The neuroprotective effects of apelin-13 suggest its therapeutic effect on neurodegenerative disorders.
International Journal of Morphology, 2009
The pyramidal cell density of CA1 hippocampal subfield following STZ-induced diabetes in young ra... more The pyramidal cell density of CA1 hippocampal subfield following STZ-induced diabetes in young rats were studied. 12 male albino 6-week Wistar rats were allocated equally in groups of normal and diabetic. Hyperglycemia induced by Streptozotocin (80 mg/kg) in animals of diabetic group. After 5 weeks of study, all the rats were sacrificed and coronal sections were taken from dorsal hippocampal formation of the right cerebral hemispheres and stained with crysel violet. The area densities of the CA1 pyramidal cells were measured and compared among two groups. No significant difference between the densities of two experimental groups was found. The results can arise from the short period of diabetes and also the possible regenerative processes in developing brain of the young diabetic rats which compensated significant diabetes-induced neuronal loss.
Folia morphologica, 2009
Diabetes mellitus is associated with cerebral alterations in both human and animal models of the ... more Diabetes mellitus is associated with cerebral alterations in both human and animal models of the disease. These alterations include abnormal expression of hypothalamic neuropeptides and hippocampal astrogliosis. Urtica dioica (Nettle) is among several species listed for their use against diabetes in folk medicine. The aim of this study was the evaluation of the astrocyte number in the dentate gyrus of diabetic rats after treatment with nettle. A total of 21 male albino Wistar rats were used in the present study. The animals were divided into three groups: control, nettle-untreated diabetic, and nettle treated diabetic. Hyperglycaemia was induced by streptozotocin (80 mg/kg) in the animals of the diabetic and treatment groups. One week after injection of the streptozotocin, the animals in the treatment group received a hydroalcoholic extract of Urtica dioica (100 mg/kg/day) for 4 weeks intraperitoneally. After a 5-week survival period, all the rats were sacrificed and coronal section...
National Journal of Physiology, Pharmacy and Pharmacology
National Journal of Physiology, Pharmacy and Pharmacology
Archives of Physiology and Biochemistry
Jundishapur Journal of Microbiology
Folia Neuropathologica, 2018
Introduction: The pharmacological suppression of luteinising hormone or human chorionic gonadotro... more Introduction: The pharmacological suppression of luteinising hormone or human chorionic gonadotropin (hCG) can reduce Aβ plaques in the brains of rats and mice, but the effects of hCG on the phosphorylated tau protein level in the hippocampus have not been studied. Therefore, we investigated the effects of hCG on the phosphorylated tau protein level and its effect on hCG receptor-immunoreactive neuron density in the hippocampus of Alzheimer's disease (AD) model rats (streptozotocin [STZ] injected intracerebroventricularly). Material and methods: The rats were administered hCG (50, 100, and 200 IU/200 µl saline, intraperitoneally) or vehicle once/day for three days after injection of STZ. The passive avoidance memory test was performed 6 hours after the last hCG injection. The phosphorylated tau protein level in the hippocampus was measured by ELISA, and hCG receptor-immunoreactive neurons were shown by immunohistochemical technique in areas of hippocampus. Results: Treatment with hCG attenuated memory deficiencies and reduced the level of phosphorylated tau protein in the hippocampus. hCG also improved the density of hCG receptor-immunoreactive neurons. The high dose of hCG hormone (200 IU/200 µl saline) seemed to have a significant effect on passive avoidance memory, phosphorylated tau protein concentration, and accumulation of hCG receptor-immunoreactive neurons in Alzheimeric rats' hippocampus. Conclusions: In conclusion, hCG can provide protection against memory deficits induced by STZ and it can inhibit accumulation of tau hyperphosphorylation in the hippocampus. Furthermore, hCG can increase the hCG receptor-ir neurons number in the rats hippocampus after ICV injection of STZ.
International Journal of Morphology, Jun 1, 2018
Parkinson's disease (PD) is described as a neurological condition, resulting from continuous dege... more 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.
Folia Neuropathologica
M1 muscarinic receptor plays a fundamental role in memory and is closely associated with Alzheime... more M1 muscarinic receptor plays a fundamental role in memory and is closely associated with Alzheimer's disease (AD); it has long been assumed as a therapeutic goal. By activating of the cholinergic receptor vitamin E helps with memory retention. But effects of vitamin E on density of M1 muscarinic receptor-immunoreactive (ir) neurons remain poorly understood. The present research aimed to examine the chronic administration effect of vitamin E against scopolamine-induced memory loss and the number of M1 muscarinic receptor-ir neurons of the hippocampus in male rats. Randomly, 42 adult male Wistar rats were divided to six groups: control, Sham-saline: receiving scopolamine + saline, Sham-sesame oil: receiving scopolamine + sesame oil and three experimental groups: receiving scopolamine + vitamin E with different doses (25, 50, and 100 mg/kg/day, i.p.) for 14 days. The passive avoidance task was used for the memory test. Twenty-four hours after behavioral tests, rats' brains were taken and fixed, and after tissue processing, sections were stained using the immunohistochemical technique for M1 muscarinic receptor-ir neurons and cresyl violet for neurons. The injection of scopolamine to rats caused memory impairment and vitamin E treatment could ameliorate it. In the scopolamine-treated groups, the number of CA1 and CA3 pyramidal and dentate gyrus (DG) granular neurons was decreased significantly as compared to the control group. Vitamin E treatment significantly increased neuron numbers in the CA1 and CA3 areas of the hippocampus and DG area. Treatment with vitamin E for 14 days could compensate the loss of M1 muscarinic receptor-immunoreactive neuron numbers induced by scopolamine in the hippocampus. The most effective vitamin E dose was 50 mg/kg/day in this study. In conclusion, vitamin E can compensate the neuronal loss in the hippocampal formation and also it can raise the density of M1 receptor-ir muscarinic neurons after an injection of scopolamine.
Jundishapur Journal of Natural Pharmaceutical Products
Anatomical science international, Jan 10, 2017
The effects of tamoxifen and soy on apoptosis of the hippocampus and dentate gyrus of ovariectomi... more The effects of tamoxifen and soy on apoptosis of the hippocampus and dentate gyrus of ovariectomized rats after repeated seizures were investigated. Female rats were divided into: (1) Control, (2) Sham, (3) Sham-Tamoxifen (Sham-T), (4) Ovariectomized (OVX), (5) OVX-Tamoxifen (OVX-T), (6)OVX-Soy(OVX-S) and (7) OVX-S-T. The animals in the OVX-S, OVX-T and OVX-S-T groups received soy extract (60 mg/kg; i.p.), tamoxifen (10 mg/kg) or both for 2 weeks before induction of seizures. The animals in these groups additionally received the mentioned treatments before each injection of pentylenetetrazole (PTZ; 40 mg/kg) for 6 days. The animals in the Sham and OVX groups received a vehicle of tamoxifen and soy. A significant decrease in the seizure score and TUNEL-positive neurons was seen in the OVX group compared to the Sham (P < 0.001). The animals in both the OVX-T and OVX-S groups had a significantly higher seizure score as well as number of TUNEL-positive neurons compared to the OVX gro...
Anatomy & Cell Biology, 2016
Anxiety, which may be understood as the pathological counterpart of normal fear, is manifested by... more Anxiety, which may be understood as the pathological counterpart of normal fear, is manifested by disturbances of mood, as well as of thinking, behavior, and physiological activity [1]. The etiology of most anxiety disorders, although not fully understood, has come into sharper focus in the recent past. Serotonergic neurocircuitry is known to be involved in the development of anxiety [2-4]. 5-HT is believed to be
International Journal of Morphology, Dec 1, 2009
The pyramidal cell density of CA1 hippocampal subfield following STZ-induced diabetes in young ra... more The pyramidal cell density of CA1 hippocampal subfield following STZ-induced diabetes in young rats were studied. 12 male albino 6-week Wistar rats were allocated equally in groups of normal and diabetic. Hyperglycemia induced by Streptozotocin (80 mg/kg) in animals of diabetic group. After 5 weeks of study, all the rats were sacrificed and coronal sections were taken from dorsal hippocampal formation of the right cerebral hemispheres and stained with crysel violet. The area densities of the CA1 pyramidal cells were measured and compared among two groups. No significant difference between the densities of two experimental groups was found. The results can arise from the short period of diabetes and also the possible regenerative processes in developing brain of the young diabetic rats which compensated significant diabetes-induced neuronal loss.
International Journal of Morphology
As neuron-astrocyte interactions play a crucial role in the adult brain, it is thought that astro... more As neuron-astrocyte interactions play a crucial role in the adult brain, it is thought that astrocytes support learning and memory through specific mechanisms. In this study, the effect of scopolamine based amnesia on the number of astrocytes in rats' hippocampus was studied. Adult male albino Wistar rats were bilaterally cannulated into the CA1 region and animals received saline or different doses of scopolamine (0.5, 1 and 2 mg/ rat, intra-CA1), immediately after training. Then all the rats were sacrificed and coronal sections were taken from the dorsal hippocampal formation of the right cerebral hemispheres and stained with PTAH. The area densities of the astrocytes in dentate gyrus were measured and compared in the all groups (p < 0.05). Data showed that post-training scopolamine (0.5, 1 and 2 µg/rat, intra-CA1) dose-dependently reduced the step-through latency in the inhibitory avoidance task, showing scopolamineinduced amnesia. Also we found different response of astrocytes in different subfields of hippocampal formation. In dentate gyrus the number of astrocytes was increased, but in other areas scopolamine can decreased the density of astrocytes. We concluded that scopolamine can cause amnesia and this phenomenon can have an effect on astrocyte numbers in the rats hippocampal formation.
International Journal of Morphology
Cholinergic system in CNS is involved in learning and memory. Scopolamine as muscarinic acetylcho... more Cholinergic system in CNS is involved in learning and memory. Scopolamine as muscarinic acetylcholine receptor antagonist is used for creation of memory impairment. The purpose of this study is evaluation of scopolamine-based amnesia on memory retention and the effect of this phenomenon on the number of neurons contains M1-receptors in the male Wistar rats hippocampal regions. Thirty-five male Wistar rats (200±20 g) were distributed randomly into five groups. Control group (intact samples) and 3 experimental groups with sham group (saline) were tested by the method of passive avoidance (shuttle box) in doses of 0.2, 0.5 and 1 mg/kg (intraperitoneally) as a single dose. After one week, memory test was taken from the rats. Finally, brains dissected from sacrificed rats, and then processed tissues were stained with antibody against M1 receptors (Immunohistochemistry technique) followed by counting of hippocampal CA1, CA3 and DG regions. Our results showed significant decrease in neurons contains M1-receptors in all area of hippocampus. We found that the less number of M1-neurons showed in 1 mg/kg dose of scopolamine. We concluded that scopolamine as muscarinic acetylcholine receptor antagonist can reduce dose-dependently the density of M1-neurons in all areas of hippocampus.
Pakistan Journal of Biological Sciences
The hippocampal formation is present in all mammalian species and it is consist of the subiculum,... more The hippocampal formation is present in all mammalian species and it is consist of the subiculum, the hippocampus and the dentate gyrus. Apart from principal neurons, the hippocampal formation contains glial cells and various types of interneurons. Glial cells in hippocampus contains the Astrocytes, microglia and oligodantrocytes. Astrocytes play a more active role in neuronal activity, including regulating ion flux currents, energy production, neurotransmitter release and synaptogenesis. Astrocytes are the only cells in the brain that contain the energy molecule glycogen. In this study 5 male albino wistar rats were used. After histological processing. The slides of the brains were stained with PTAH staining for showing the astrocytes. We showed differences in number of astrocytes in different compartment of hippocampus. There is significant difference between CA1 and CA3 and also between CA2 and CA3 areas. We concluded that functional differences can due to structural differences.
International Journal of Morphology, 2012
Radiation therapy of the brain is associated with many consequences, including cognitive disorder... more Radiation therapy of the brain is associated with many consequences, including cognitive disorders. Pathogenesis of radiation induced cognitive disorder is not clear, but reduction of neurogenesis in hippocampus may be an underlying reason. 24 adult male rats entered to study. Radiation absorbed dose to midbrain was 10 Gy, delivered by routine cobalt radiotherapy machine which its output was measured 115.24 cGy/min. The rats were divided in four groups of sixes, including groups of control, single fraction 10 Gy, fractionated 10 Gy and finally anaesthesia sham group. Number of pyramidal nerve cells was counted in two regions of hippocampus formation (CA1 and CA3). The radiation could reduce the number of cells in two regions of hippocampus significantly (p=0.000). It seems fractionated 10 Gy irradiation to more efficient than single fraction, while role of anaesthesia drug should be cautiously assessed. Moreover the rate of neurogenesis reduction was determined the same in these regions of hippocampus meaning the same radiosensitivity of cells.
International Journal of Morphology, 2013
Several animal model studies have shown that Diabetes mellitus can affect on the activity of hipp... more Several animal model studies have shown that Diabetes mellitus can affect on the activity of hippocampus astrocytes, but these studies reported controversial findings. This study was done to evaluate the preventive and treatment effect of Urtica dioica (U. dioica) on astrocytes density in the CA1 and CA3 subfields of hippocampus of streptozotocin (STZ) induced diabetic rats. Twenty-eight male albino Wistar rats were randomly allocated equally into control, diabetic, U. dioica treatment and U. dioica preventive groups. Hyperglycemia was induced by STZ (80 mg/kg/BW). One week after injection of the streptozotocin, animals in treatment group were received hydroalcoholic extract of U. dioica (100 mg/kg/BW /day) for 4 weeks by intraperitoneally. In preventive group, diabetic rats were received 100 mg/kg/BW/ daily hydroalcoholic extract of U. dioica for 5 days before STZ injection. Then, animals were sacrificed and coronal sections were taken from the right dorsal hippocampus, stained with PTAH. The area densities of the astrocytes were measured. The number of astrocytes in CA1 of controls, diabetic treatment and preventive groups was 19.00±5.5, 17.14±6.4, 21±8.1 and 16.48±3.2, respectively. The densities of astrocytes in CA3 of controls, diabetic, treatment and preventive groups were 25.45 ±7.60, 21.54±7.5, 23.75±5.6 and 19.89±3.8, respectively. The density of astrocytes in diabetic rats reduced in comparison with controls (P<0.05). In CA1 and CA3, in spite of preventive administration, treatment of diabetic rats with U. dioica significantly increased the astrocytes. This study showed that treatment with U. dioica extract can help compensate for the CA1 and CA3 subfields of hippocampus astrocytes in diabetic rats.
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Papers by Mehrdad Jahanshahi
Methods: Male rats (n=40) were assigned to 5 groups of 8. No intervention was considered for the control group. The scopolamine group received stereotaxic surgery and was treated with 3 mg/kg scopolamine intraperitoneally. The treatment groups were treated with scopolamine plus intraventricular injection of apelin-13 (1.25, 2.5, and 5 µg) into the right lateral ventricles for 7 days. For evaluating the memory impairment, the passive avoidance reactions of the animals, except the control group, were assessed 24 hours following the last injection. Regarding histological analysis, Congo red staining of the hippocampal sections was done, and immunoblotting was used to determine apoptotic biochemical markers, including caspase 3, cytochrome C, and congophilic amyloid-beta plaques.
Results: Apelin–13 alleviated scopolamine-related passive avoidance memory impairment and reduced the number of congophilic amyloid-beta plaques in the hippocampus (all P<0.001). It attenuated the decrease in the mean levels of hippocampal apoptotic proteins (caspase 3, cytochrome C) in animals treated with scopolamine (all P<0.05).
Conclusion: The neuroprotective effects of apelin-13 suggest its therapeutic effect on neurodegenerative disorders.
Methods: Male rats (n=40) were assigned to 5 groups of 8. No intervention was considered for the control group. The scopolamine group received stereotaxic surgery and was treated with 3 mg/kg scopolamine intraperitoneally. The treatment groups were treated with scopolamine plus intraventricular injection of apelin-13 (1.25, 2.5, and 5 µg) into the right lateral ventricles for 7 days. For evaluating the memory impairment, the passive avoidance reactions of the animals, except the control group, were assessed 24 hours following the last injection. Regarding histological analysis, Congo red staining of the hippocampal sections was done, and immunoblotting was used to determine apoptotic biochemical markers, including caspase 3, cytochrome C, and congophilic amyloid-beta plaques.
Results: Apelin–13 alleviated scopolamine-related passive avoidance memory impairment and reduced the number of congophilic amyloid-beta plaques in the hippocampus (all P<0.001). It attenuated the decrease in the mean levels of hippocampal apoptotic proteins (caspase 3, cytochrome C) in animals treated with scopolamine (all P<0.05).
Conclusion: The neuroprotective effects of apelin-13 suggest its therapeutic effect on neurodegenerative disorders.