The role of hippocampal 5-HT1D and 5-HT1F receptors on learning and memory in rats.

Serotonin is a neurotransmitter, which is involved in memory via its receptors. The 5-HT1D and 5-HT1F receptors mainly exist in the hippocampus, which plays an important role in memory processing. However, few studies have assessed the effect of these serotonin receptors on memory. We evaluated the effect of a 5-HT1D receptor agonist, PNU142633, 5-HT1D receptor antagonist, BRL15572 hydrochloride, and 5-HT1F receptor agonist, LY344864, on the recognition and avoidance memory in the hippocampus area. Fifty adult male Wistar rats weighing 200-250 g were divided into the control, sham-operated, PNU, BRL, and LY groups (n=10 per group). Bilateral guide cannulas were implanted into the dentate gyrus area of the hippocampus. The drugs were administered at the dose of 1 µg/µl before the novel object recognition (NOR) and passive avoidance learning (PAL) tests. The results showed that in the NOR test, the administration of PNU and LY had no significant effect on recognition index; however, the recognition index was increased by BRL. In the PAL test, the administration of PNU had no significant effect on recognition index, but the administration of BRL and LY increased the time spent in the dark compartment of the apparatus and decreased the step-through latency into the dark compartment apparatus. It can be concluded that the inhibition of the hippocampal 5-HT1D receptor improved cognition memory but impaired avoidance memory. Activation of the hippocampal 5-HT1F receptor had no effect on cognitive memory but impaired avoidance memory.

The effects of polyvinyl alcohol-coated selenium nanoparticles on memory impairment in rats.

Some mineral elements exert beneficial neuroprotection, especially in the form of nanoparticles. The aim of the present study was to evaluate the effects of selenium nanoparticles (SeNPs) and polyvinyl alcohol (PVA)-coated SeNPs (PVA-SeNPs) on Alzheimer's disease (AD) in a rat model of AD. Twenty-eight rats were randomly divided into four groups of seven rats: control, Alz, Alz + Se, and Alz + Se-PV groups. PVA-SeNPs and SeNPs were chemically synthesized and orally administrated (0.4 mg/kg) to the AD rats for one month. AD was induced by an intracerebroventricular (ICV) injection of streptozotocin (STZ). The memory function was assessed by the novel object recognition (NOR) and passive avoidance learning (PAL) tests. The expression of hippocampal brain-derived neurotrophic factor (BDNF) and stress oxidative markers (MDA and TAC), and the number of amyloid-beta (Aß) plaques were assessed using ELISA kits, biochemical methods, and Congo red staining, respectively. The results of the behavioral tests showed that the discrimination index in the NOR test increased in the Alz + PVA-SeNPs group compared to the Alz group. Memory performance in the PAL task improved in the PVA-SeNPs and SeNPs groups compared to the Alz group. The level of the BDNF in both of the Alz treatment groups (PVA-SeNPs and SeNPs) showed a significant increase compared to the Alz group. MDA levels and Aß plaques decreased in both NPs-treated Alz groups, while TAC levels decreased in all Alz groups. PVA-SeNPs were more effective than SeNPs in the improvement of the cognition deficit. The results suggest that PVA-SeNPs improve the cognition and memory deficit induced by an ICV injection of STZ through a decrease in the number of Aß plaques and malondialdehyde levels and an increase in the BDNF levels.

Deferoxamine preconditioning enhances the protective effects of stem cells in streptozotocin-induced Alzheimer's disease.

AIMS: Stem cell-based therapy is one of the promising strategies in the treatment of Alzheimer's disease (AD), but the short lifespan and low homing of transplanted cells continue to be a major obstacle in this method. Preconditioning of stem cells before transplantation could increase cell therapy efficiency. Herein, we examined whether the treatment of stem cells with deferoxamine (DEF) prior to graft could enhance the neuroprotective effects of stem cells in the streptozotocin (STZ)-treated male rats. MATERIALS AND METHODS: After induction of the AD model, the rats were transplanted with DEF-preconditioned Adipose-derived mesenchymal stem cells (AMSCs) or untreated cells. Memory function, antioxidant capacity, cell density, and homing of transplanted cells were assessed using Morris water maze and shuttle box tasks as well as biochemical and histochemical methods. KEY FINDINGS: Transplantation of AMSCs caused a memory improvement when compared to the AD model. The injection of DEF-preconditioned AMSCs was more effective in improving learning and memory than the untreated cells through an increase in the antioxidant capacity. Moreover, the homing of transplanted cells was higher in the rats that received the preconditioned cells than that of the naïve cell-injected group. SIGNIFICANCE: It seems that the transplantation of DEF-treated cells may increase the efficiency of stem cells via an increase in the antioxidant capacity.

Synergistic effects of adipose-derived mesenchymal stem cells and selenium nanoparticles on streptozotocin-induced memory impairment in the rat.

AIMS: Memory impairment is determined to be the most well-known symptom of Alzheimer's disease (AD). Although cell therapy seems is an efficient therapeutic strategy to attenuate the AD-related memory impairment, transplanted cells have a short lifespan and do not survive long term in the recipient animals. Herein, we investigated whether the combination therapy of Selenium nanoparticles (SeNPs) and stem cells attenuates the neurotoxicity in an AD animal model. MATERIAL AND METHODS: The adipose-derived mesenchymal stem cells (AMSCs) were transplanted in the AD model. In addition to cell injections, the animals also received oral administration of SeNPs (0.4 mg/kg) for one month. Recognition memory, cell survival, and BDNF concentration were assessed using the novel object recognition task, immunofluorescence, and ELISA methods. KEY FINDINGS: Our results showed that the combined therapy was more effective in increasing the discrimination index than the administering SeNPs or AMSCs alone. Moreover, SeNPs and stem cells together had the greatest effects in reducing the deposition of Aß and increasing the concentration of BDNF. Ultimately, the survival and proliferation of transplanted cells were more in the group that received stem cells besides SeNPs. SIGNIFICANCE: Taken together, it seems that the transplantation of MSCs combined with SeNPs could achieve better results in the neuroprotection in the AD model than a conventional treatment of SeNPs or stem cells alone.

Protective Effects of 5-HT1A Receptor Inhibition and 5-HT2A Receptor Stimulation Against Streptozotocin-Induced Apoptosis in the Hippocampus.

INTRODUCTION: Intracerebroventricular administration of streptozotocin (icv-STZ) induced apoptosis changes in neurons similar to Alzheimer's disease. The serotonergic system via its receptor involved in survival of neurons. The present study examined the ability of selective 5-HT1A receptor antagonist (NAD-299) and 5-HT2A receptor agonist (TCB-2) to attenuate the apoptosis caused by the icv-STZ in the rat. METHODS: The icv-STZ (3 mg/kg, 10 µL, twice) induced neuronal loss in the hippocampus of adult male rats. Animals were divided into naive control, sham-operated, STZ+saline (1 µL, icv), STZ+NAD-299 (5 µg/µL, icv), STZ+TCB-2 (5 µg/µL, icv), and STZ+NAD-299+TCB-2 (5 µg/µL of any agent, icv) groups. Following the 35 days' treatment period, neuronal apoptosis was detected using the Tunnel. Cells with morphological features of apoptotic cell were contended by microscopy. RESULTS: TCB-2 and NAD-299 administration decreased number of apoptotic neurons in the treatment group compared with the STZ group. Combined treatment of STZ rat with NAD+TCB more decreased number of apoptotic cells in compare to TCB-2 or NAD-299 treated STZ groups. CONCLUSION: Treatment with 5-HT1A receptor antagonist or 5-HT2A receptor agonist diminished apoptosis. The beneficial effect of 5HT1A receptor inhibition was potentiated with activation of 5-HT2A receptor in prevention of apoptosis in hippocampus.

Protective effects of 5-HT1A receptor antagonist and 5-HT2A receptor agonist on the biochemical and histological features in a rat model of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder and neuropathologically characterized by the aggregation of amyloid-beta (Aß) plaques, neurofibrillary tangles, enhanced oxidative stress and neurodegeneration. Involvement of serotonergic systems in AD has been supposed and it is suggested that serotonin receptors modulation may provide a novel therapeutic target for AD. This study aimed at investigating the protective effect of NAD-299 (the selective 5-HT1A receptor antagonist) and TCB-2 (the potent5-HT2A receptor agonist) on the hippocampal oxidative stress biomarkers and the number of intact neurons in streptozotocin (STZ)-induced Alzheimer's disease in rats. Fifty adult male Wistar rats weighing 250-300 g were divided into five groups: sham, STZ-treated, STZ + NAD-299 (5 µg/1 µl icv), STZ + TCB-2 (5 µg/1 µl icv) and STZ + NAD-299 (5 µg/0.5 µl icv) +TCB-2 (5 µg/0.5 µl icv). At the end of the study, the rats were weighed, then hippocampal oxidative stress markers [total antioxidant capacity (TAC), malondialdehyde (MDA), the total thiol group (TTG), and DNA damage] were measured. In addition, the number of intact neurons in the CA1 area of the hippocampus was determined using hematoxylin and eosin staining. The results showed that icv injection of STZ reduced hippocampal TAC, TTG levels and intact pyramidal cells and increased DNA damage and MDA levels in the hippocampus of STZ-treated rats. Icv administration of NAD-299, TCB-2, and NAD-299+TCB-2 increased TAC and TTG contents and hippocampal intact neurons and reduced hippocampal DNA damage, MDA levels in icv-STZ treated rats. Moreover, there was no significant difference in weight changes among the experimental groups. According to the obtained results, it is suggested that 5-HT1A receptor antagonist (NAD-299) and 5-HT2A receptor agonist (TCB-2) can reduce oxidative stress and neuronal loss in a rat model of AD and may prevent the AD progression.

The effect of NAD-299 and TCB-2 on learning and memory, hippocampal BDNF levels and amyloid plaques in Streptozotocin-induced memory deficits in male rats.

RATIONALE: Alzheimer's disease (AD) is the most common form of dementia characterized by a progressive decline in cognitive function. The serotonergic system via the 5-HT1A receptor and 5-HT2A receptor is proposed to affect the cognitive process. OBJECTIVE: In the present study, the effects of NAD-299 (5-HT1AR antagonist) and TCB-2 (5-HT2AR agonist) on learning and memory processes, hippocampal brain-derived neurotrophic factor (BDNF) levels, neuronal necrosis, and Aß plaque production have been investigated on the intracerebroventricular (icv) injection of streptozotocin (STZ)-induced memory deficits in rats. METHODS: Fifty-four adult male Wistar rats (250-300 g) were divided into six groups (n = 9 in each group): control, sham-operated, AD (icv-STZ (3 mg/kg, 10 µl)), AD+NAD-299 (5 µg/1 µl icv for 30 days), AD+TCB-2 (5 µg/1 µl icv for 30 days), and AD+NAD-299 + TCB-2 (NAD-299 (5 µg/0.5 µl icv) and TCB-2 (5 µg/0.5 µl icv) for 30 days). Following the treatment period, rats were subjected to behavioral tests of learning and memory. Then, hippocampal BDNF, amyloid-beta (Aß) plaque, and neuronal loss were determined by ELISA Kit, Congo red staining, and Nissl staining, respectively. RESULTS: The results of behavioral tests showed that icv-STZ injection decreased the discrimination index in the novel object recognition (NOR) test. In the passive avoidance learning (PAL) task, icv-STZ injection significantly decreased step-through latency (STLr) and increased time spent in dark compartment (TDC). Treatment with NAD-299, TCB-2, and NAD-299 + TCB-2 attenuated the STZ-induced memory impairment in both NOR and PAL tasks. icv-STZ induced a decrease in hippocampal BDNF levels and increased Aß plaques production in the brain, whereas treatment with NAD-299, TCB-2, and NAD-299 + TCB-2 reduced Aß plaques in the brain and increased the hippocampal BDNF level. Results of Nissl staining showed that icv-STZ injection increased neuronal loss in the hippocampus, while treatment with NAD-299, TCB-2, and NAD-299 + TCB-2 reduced hippocampal neurodegeneration. CONCLUSION: These findings suggest that 5-HT1AR blockade by NAD-299 and 5-HT2AR activation by TCB-2 improve cognitive dysfunction in icv-STZ-treated rats, and these drugs may potentially prevent the progression of AD.

Effect of oral administration of fenitrothion on biochemical and hematological parameters in rats.

The aim of this study was to evaluate the effects of acute exposure to various doses of fenitrothion (FNT) on level of serum glucose, total protein, triglycerides (TG), total cholesterol (TC) and some hematological parameters. The study was conducted on 8-week-old male Wistar rats that divided into four groups (three experimental groups and one control group), were treated orally with different doses (25, 50 and 100 mg kg(-1)) of fenitrothion for 28 consecutive day. After treatment, blood samples were collected for biochemical and hematological studies. Present results demonstrated that exposed groups led to significant dose-dependent increase in serum glucose and cholesterol levels. Significant decrease was observed in some hematological parameters [Red Blood Cell (RBC) counts, Hemoglobin (Hb), Haematocrite (Ht) and Mean Corpuscular Hemoglobin (MCH) values]. Serum total protein and triglycerides were also decreased not significantly in exposed groups when compared with control. Generally, the degrees of observed variations were found to be dose dependent.