nasrin hashemi-firouzi

Mesenchymal stem cell (MSC) transplantation represents a promising approach for treating Alzheimer’s disease (AD). These stem cells, however, have a short lifespan following transplantation into recipient animals. Selenium nanoparticles, due to their size, aid in drug delivery for brain disorders. This study investigated the therapeutic effect of MSCs and polyvinyl alcohol (PVA)-coated selenium nanoparticles (SeNPs) in a rat model of AD.

An Alzheimer-like phenotype was induced through intracerebroventricular (ICV) administration of streptozotocin (STZ).  Rats were assigned to five groups: control, Alz (STZ; 3 mg/kg, 10 μl, ICV), Alz+stem cell (ICV transplantation), Alz+SeNP (0.4 mg/kg, orally), and Alz+stem cell+SeNPs. The ICV administration of STZ mimicked some aspects of AD in the Alz groups. SeNPs were administrated for 30 days following STZ administration. The novel object recognition (NOR) and passive avoidance learning (PAL) tests were used to evaluate cognition and memory. Oxidative stress biomarkers and brain-derived neurotrophic factor (BDNF) were assessed by biochemical analysis, ELISA kits, and Congo red staining, respectively. 

The combined therapy of PVA-coated SeNPs and MSC transplantation was more effective in enhancing memory reacquisition compared to either SeNPs or MSCs alone. The use of stem cells in conjunction with PVA-coated SeNPs significantly boosted anti-oxidant capacity.

The results suggest that the joint treatment with PVA-coated SeNPs and MSCs offers considerable neuroprotection against AD in animal models.

Serotonergic system has a role in morphine dependence and withdrawal symptoms via its receptors. On the other hand, the effect of 5-HT2A receptor on withdrawal symptoms has not been evaluated completely. The aim of this study was to investigate the effect of 5-HT2A receptor stimulation on morphine withdrawal symptoms in male mice.

This experimental study included twenty eight male NMRI mice (20-25g). Morphine dependency was induced in a five- day schedule by 6, 16, 26, 36, 46, 56 and 66 mg/kg doses respectively. On the fifth day, 2 hours after a single dose of morphine, naloxone was injected (3 mg/kg) and the scores (from 0 to 3) of withdrawal symptoms including number of jumps, teeth chattering, writing, head shakes, limbs shakes, and percentage of body weight loss were recorded for 30min.The treatment group received different doses of TCB-2 (03, and 2.5mg/kg; Intraperitoneally).

Withdrawal symptoms in the morphine-dependent mice were significantly more frequent than those in the control mice. Different doses of TCB-2 significantly increased some of the morphine withdrawal symptoms in the experimental groups.

The present study indicated that stimulation of 5-HT2A receptor via its agonist exacerbated the morphine withdrawal symptoms. Further studies are recommended to better understand the role of the 5-HT2A receptor in morphine dependence and withdrawal.

Learning and memory may decline due to Alzheimer’s disease (AD) in older adults. A reduction in cyclic guanosine monophosphate concentration and an increase in phosphodiesterase activity have been reported in the process of aging. Although phosphodiesterase (PDE) type 5 inhibitor, Tadalafil is used to treat erectile dysfunction; PDE inhibitors possibly prevent cognition impairment in aging. This study was designed to investigate the effects of tadalafil on memory in middle-aged and young healthy and AD rats.

Memory impairment was induced by intracerebroventricular (ICV) administration of streptozotocin (STZ; 3 mg/kg) in AD rats. Male Wistar rats (middle-aged and young) were distributed into six groups as follows: two control, two AD, and two AD+tadalafil (1 mg/kg) groups. Saline or tadalafil was administered once a day orally for 40 consecutive days. Animals were tested using novel object recognition (NOR), passive avoidance learning (PAL), and Morris water maze (MWM) tests.

Aged AD rats exhibited a significant impairment in cognition in the NOR test and impaired learning and memory in PAL and MWM tests compared with the control aged rats. Tadalafil treatment in aged AD rats significantly improved the discrimination index in the NOR test, decreased the time spent in the dark compartment in the PAL test, and increased time spent in the target quadrant in MWM tests compared with aged AD rats. In young AD rats, treatment with tadalafil significantly enhanced cognition, learning, and memory in the NOR, PAL, and MWM tests compared with young AD rats treated with saline.

Tadalafil treatment in aged rats improves cognition and memory after STZ-induced (ICV) memory impairment.It can be concluded that chronic treatment with tadalafil is protective against cognitive, learning, and memory impairment in both young and aged subjects.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with impaired cognitive skills and learning and memory dysfunctions.  It has been suggested that pelargonidin (PG), as an antioxidant agent, has a neuroprotective effect. PG could prevent damaging effects of amyloid-beta (Aβ) deposition. The aim of this study was to determine the chronic effect of PG on hippocampal neurons and memory processes in a rat model of AD.

Twenty-eight male adult rats were divided into sham, AD, AD+PG (5 μg, intracerebroventricular), and PG (5 μg, intracerebroventricular) groups. Intracerebroventricular (ICV) injection of Aβ peptides (6 μg) was done using stereotaxic surgery. ICV administration of PG or saline was performed daily for 28 consecutive days. Behavioral analysis was performed using the novel object recognition (NOR) and passive avoidance tests. Neuronal apoptosis was detected using TUNEL assay in the hippocampus.

The ICV injection of Aβ reduced step-through latency and discrimination index in behavioral tests (p <0.001). Aβ increased the number of apoptotic neurons (p <0.001). PG treatment decreased the time spent in the dark compartment and neuronal apoptosis in the AD+PG rats (p <0.001). PG increased the discrimination index in the NOR test (p <0.001).  Although PG did not change behavioral variables, it decreased cell death in the PG group.

PG attenuated neuronal apoptosis and improved cognition and memory deficiency in AD rats. The protective effect of PG against Aβ may be due to its anti-apoptotic property. It is suggested that PG can be useful to treat AD.

Alzheimer's disease (AD) is characterized by progressive cognitive decline. Oxidative stress plays a central role in the pathogenesis of AD. It has been proposed that administration of antioxidants affect cognitive processes, such as learning and memory. This study investigated the protective effects of vitamin E and Ginkgo biloba extract (as antioxidants) on learning and memory, hippocampal plasticity, and apoptotic marker proteins in a rat model of AD.

The hyroalcoholic extract of Gingko biloba leaves wasprepared using maceration method. Male Wistar rats were randomly divided into six groups: control, sham received intra-hippocampal injection (I.H.P) of vehicle, AD model that received intra-hippocampal injection of the beta-amyloid (Aβ), AD+ vitamin E (200 mg/kg, i.p.), AD+ G. biloba (100 mg/kg/p.o.), and AD+ vitamin E (200 mg/kg, i.p.)+ G. biloba (100 mg/kg/p.o.). At the end of the treatments, the rats were subjected to the passive avoidance learning (PAL) test. The field long wterm potentials (LTP) were recorded in the hippocampal dentate gyrus. Hippocampal expressions of Bax and Bcl-2 (as pro-apoptotic, as anti-apoptotic) proteins were measured by western blot method.

Treatment with G. biloba and vitamin E improved the Aβ-induced memory impairment in the PAL task. Vitamin E and/or G. biloba extract enhanced the population spike amplitude evoked potentials of the LTP components, vitamin E and/or G. biloba extract increased Bcl-2 expression and decreased Bax expression in the hippocampus.

Ginkgo biloba and vitamin E could suppress the expression of apoptosis markers and improved hippocampal LTP impairment and the memory deficit induced by Aβ.

3, 4- methylenedioxymethamphetamine (MDMA) is used for recreational purposes worldwide. The use of MDMA resulted in learning and memory dysfunction. Duloxetine, a serotonin/noradrenalin-reuptake inhibitor is also utilized to treat depression and anxiety. The current study aimed to evaluate the effects of duloxetine against MDMAchr('39')s effect on anxiety, cognition, and memory disturbance in the male rats.

Wistar rats received treatment of saline (10 ml/kg; sham group), “MDMA” (10 mg/kg), “Duloxetine” (10 mg/kg), and Duloxetine plus MDMA (10 mg/kg, each), or no treatment (control) through the intraperitoneal administration for four days. The elevated plus maze (EPM), passive avoidance learning (PAL), Morris water maze (MWM), and novel object recognition (NOR) tests were employed to evaluate the anxiety, memory, and cognition,  

The MDMA increased the time spent in open arms in EPM, time spent in the dark part of PAL, and swimming time to reach the platform in MWM. Furthermore, duloxetine inhibited the reduction of the discrimination index, time spent in the dark compartment, and time spent on the platform in NOR, PAL, and MWM tests among rats received MDMA. Moreover, duloxetine decreased time spent in open arms and the target quadrant in EPM and MWM tests.

Our findings suggested that duloxetine treatment attenuated the MDMA-induced anxiolytic response and could improve MDMA-induced cognitive impairment and disturbance in learning and memory.

Cholinergic dysfunction is involved with age-related cognitive deficits and Alzheimer’s disease. Donepezil is a reversible acetylcholinesterase inhibitor. 

The present study examined the ability of chronic supplementation with donepezil on the cognition of the healthy young rats.

Twenty young male Wistar rats (140-160 g) were divided into the control and experimental groups. The rats received the oral administration of saline or 0.3 mg/kg of donepezil for 30 consecutive days. Then, they were trained and tested with Inhibitory Avoidance (IA) and 8-radial Arm Maze (RAM) tasks.

There was neither significant difference in the number of trials to acquisition in the IA nor the number of baited food arms in RAM tasks between the groups. In the IA retrieval test, the time spent in the dark compartment in the donepezil-treated group was significantly less than the saline-treated group. Also, in the RAM retrieval test, the number of total memory and working memory errors of donepezil-treated rats was significantly less than that of the saline-treated ones.

The chronic administration of donepezil (0.3 mg/kg) had no significant effect on the learning process, but it can improve memory performance in normal rats.

Mesenchymal stem cells (MSC) from various sources have the potentials to positively affect regenerative medicine. Furthermore, pre-conditioning strategies with different agents could improve the efficacy of cell therapy. This study compares the effects of an anti-inflammatory and antioxidant agent, melatonin, on protection of bone marrow-derived MSCs (BMSCs) and adipose tissue-derived MSCs (ADSCs).
In this experimental study, rat BMSCs and ADSCs were isolated and expanded. Pre-conditioning was performed with 5 µM melatonin for 24 hours. Cell proliferation and viability were detected by MTT assay. Expression of BAX, BCL2, melatonin receptors and osteocalcin genes were evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR). Also, apoptosis was detected with tunnel assay. Osteogenic differentiation was analyzed using alizarin red staining.
No significant increase was found in cell viability between BMSCs and ADSCs after melatonin preconditioning. Following melatonin preconditioning, BAX expression was significantly down-regulated in both ADSCs and BMSCs (P Here we have shown that the effects of preconditioning on melatonin expression in ADSCs are higher than those in BMSCs. These findings could be used in adoption of a proper preconditioning protocol based on the sources of MSCs in specific clinical applications, especially in bone regeneration.

Hyperlipidemia and low antioxidant levels is one the diabetes side effects. Some studies have indicated the possible effects of nutrients on the improvement of hyperlipidemia, by their antioxidants ingredients.
The aim of the present study was to evaluate the effect of the synthetic antioxidant, tempol, on blood lipid profiles and glucose levels in healthy and diabetic rats.
Adult Wistar rats were randomly divided to four experimental groups including, healthy control, diabetic control, diabetic receiving tempol and healthy receiving tempol groups. Diabetes was induced by injection of streptozotocin (60 mg/kg, Intraperitoneally (IP)). The rats were then fed saline or tempol (30 mg/kg) by gavage for 60 days. Blood samples were collected by cardiac puncture. Next, glucose, high-density lipoprotein (HDL), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), cholesterol, triglyceride and HbA1c were measured by specific kits. Also, the coronary risk index was calculated.
The blood glucose level increased following diabetes induction. The level of blood glucose in the diabetic receiving tempol group decreased compared to the control diabetic group. The comparison of LDL, VLDL, cholesterol, triglyceride, HbA1c and coronary risk index among experimental groups indicated the increase of these factors in the diabetic group. High-density lipoprotein in the diabetic groups was lower than the other groups..
It can be concluded that tempol can improve dyslipidemia and may decrease hyperglycemia in diabetes. It seems that antioxidants such as tempol can improve dyslipidemia and may decrease hyperglycemia in diabetes..

Anxiety disorders are frequently common neuropsychiatric disorders. Herbal medicines are widespread and used universal as a treatment compound for anxiety. The present study investigated the effects of hydro‑alcoholic extract of Salix aegyptiaca blossom on rat behavior in the elevated plus‑maze (EPM) and compared results with the effects of diazepam, as a positive control drug.

Seventy adult male Wistar rats were divided into seven groups (N = 10). Animals received S. aegyptiaca extract (25, 50, 100 mg/kg) or Diazepam (0.3, 0.6, or 1.2 mg/kg) intraperitoneally and the control group was given the vehicle (10 ml/kg) 30 min before submitting into plus‑maze test. The number of entries into the open and closed arms, the percentage of entries into the open arms of the EPM, and the time spent in the open arms were recorded.

The results revealed significant increases in percentage of entries into the open arms(P < 0.01) and in the time spent in the open arms (P < 0.01) after administration of diazepam (0.3, 0.6) and S. aegyptiaca (50, 100 mg/kg) in compare with control group. S. aegyptiaca extract has no effects on the total distance covered by animals and number of closed arms entries, whereas diazepam decreased these parameters. The locomotor activity was not significantly changed by S. aegyptiaca.

Single‑session administration of optimum doses of total extract of S. aegyptiaca has anxiolytic effects in rat similar to the low dose of diazepam. More research is needed for better understanding of anxiolytic properties and neurobiological mechanisms of action and probable interactions of S. aegyptiaca extract with neurotransmitters.

Previous studies have shown that cannabinoidergic system is involved in anxiety. However, there are controversial reports in the experimental studies. The aim of this study is to evaluate the effect of pharmacological stimulation or blocking of CB1 receptors and inhibition of endocannabinoid degradation in anxiety like behavior in elevated plus-maze (EPM) test in rat. The EPM is one of the most widely used animal models of anxiety. Male Wistar rats were randomly allocated to ten groups. Different groups of animals intraperitoneally received Win-55212 (0.3, 1 and 5 mg/kg) as CB1 receptor agonist, AM- 251 (0.3, 1 and 5 mg/kg) as CB1 receptor antagonist, URB-597 (0.03, 0.1 and 0.3 mg/kg) as endocannabinoid breakdown inhibitor or saline (as control group) 30 min before submitting into EPM test. The results showed that compared to the control group, Win-55212 (1 and 5 mg/kg) and URB-597 (0.1 and 0.3 mg/kg) significantly increased both of the time and percentage of entries into open arms. AM-251 (1 and 5 mg/kg) significantly decreased the time and percentage of entries into open arms in the EPM test. These substances have no effects on the total distance covered by animals and number of closed arm entries. It is concluded that activation of cannabinoid receptor exert anxiolytic effect while blocking of cannabinoid receptor resulted in anxiety behavior. The locomotor activity was not significantly changed by cannabinoid system. It is suggested that potentiation of cannabinoid system may be therapeutic strategy for the anxiety behavior.

Sildenafil, a phosphodiesterase-5 (PDE5) inhibitor, may have various effects on the central nervous system via the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway. Preclinical studies have shown the controversial effect of sildenafil on anxiety-like behavior in animals. This study was undertaken to investigate the acute effect of sildenafil on anxiety-like behavior in mice. Male mice were intraperitoneally (i.p.) administrated sildenafil (1, 2, or 10 mg/kg), and the control group was given the vehicle 15 min before the plus-maze test. The number of entries into the open arms of the plus-maze, the time spent in the open arms, and the total numbers of entries into the arms were recorded. The results indicated that compared to the control group, the sildenafil-treated mice spent more time in the open arms and had a greater number of entries into open arms. The total number of entries into the arms did not significantly differ between the sildenafil-treated groups and the control group. Acute administration of sildenafil could have anxiolytic effects on male mice. This effect might be mediated in a time-dependent manner by the NO/ cGMP/PDE5 pathway.