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This study investigated physical proximity and paracrine activity of neurotrophic factor-secreting cells (NTF-SCs) on beta-amyloid treated cells. Mesenchymal stem cells (MSCs) - to-NTF-SCs (Astrocyte -like cells) trans-differentiation was confirmed using immunofluorescence staining of GFAP. BDNF and NGF levels were measured by ELISA. To mimic AD-like condition, SH-SY5Y cells were exposed to 10 μM Aβ1-42. SH-SY5Y cells were allocated into Control; and Aβ1-42-treated cells. Treated cells were further classified into three subgroups including Aβ1-42 cells, Aβ1-42 cells + NTF-SCs (CM) and Aβ1-42 cells + NTF-SCs co-culture. Cell viability was measured by MTT assay. Anti-inflammatory and anti-tau hyperphosphorylation effects of NTF-SCs were assessed via monitoring TNF-α and hyperphosphorylated Tau protein expression level respectively. To explore the impact of NTF-SCs on synaptogenesis and synaptic functionality, real-time PCR assay was performed to measure the expression of synapsine 1, homer 1 and ZIF268. The level of synaptophysin was monitored via immunofluorescence staining. Data showed MSCs potential in trans-differentiating toward NTF-SCs indicated with enhanced GFAP expression (p 0.05). ELISA assay confirmed the superiority of NTF-SCs in releasing NGF and BDNF compared to the MSCs (p 0.05). Aβ significantly induced SH-SY5Y cells death while juxtacrine and paracrine activity of NTF-SCs significantly blunted these conditions (p 0.05). Trans-differentiated cells had potential to reduce Tau hyperphosphorylation and TNF-α level after treatment with Aβ through juxtacrine and paracrine mechanisms (p 0.05). Moreover, NTF-SCs significantly increased the expression rate of synapsin 1, homer 1 and zif 268 genes in Aβ-treated cells compared to matched-control group coincided with induction of synaptophysin at the protein level(p 0.05). NTF-SCs reversed AD-like neuropathological alterations in SH-SY5Y cells via paracrine and juxtacrine mechanisms.

Despite the poor regenerative capacity of the adult central nervous system (CNS) in mammals, two distinct regions, subventricular zone (SVZ) and the subgranular zone (SGZ), continue to generate new functional neurons throughout life which integrate into the pre-existing neuronal circuitry. This process is not fixed but highly modulated, revealing many intrinsic and extrinsic mechanisms by which this performance can be optimized for a given environment. The capacity for self-renewal, proliferation, migration, and multi-lineage potency of neural stem cells (NSCs) underlines the necessity of controlling stem cell fate. In this context, the native and local microenvironment plays a critical role, and the application of this highly organized architecture in the CNS has been considered as a fundamental concept in the generation of new effective therapeutic strategies in tissue engineering approaches. The brain extracellular matrix (ECM) is composed of biomacromolecules, including glycosaminoglycans, proteoglycans, and glycoproteins that provide various biological actions through biophysical and biochemical signaling pathways. Herein, we review predominantly the structure and function of the mentioned ECM composition and their regulatory impact on multiple and diversity of biological functions, including neural regeneration, survival, migration, differentiation, and final destiny of NSCs.

Known as a main neural MAP (microtubule associated protein), tau protein contributes to stabilizing microtubules involved in cellular transmission. Tau dysfunction is mainly associated with neurodegenerative diseases, particularly Alzheimer's disease (AD). In these patients, all the six tau isoforms, which are in hyperphosphorylated form, are first aggregated and then polymerized into neurofibrillary tangles inside the brain. Tau protein detected in cerebrospinal fluid (CSF) is significantly correlated with AD and is well recognized as a hallmark of the disease. Served for detection of analytes of interest, biosensor device comprises a physical transducer and a keen biological recognition component. Qualitative and quantitative evaluations may be performed through analyzation of the data, which is gathered by measurable signals converted from biological reaction. Antibodies, receptors, microorganisms, nucleic acids, enzymes, cells and tissues, as well as some biomimetic structures, normally constitute the biosensor biological recognition part. Production of nanobiosensor, which was made possible through several accomplishments in nano- and fabrication technology, opens up new biotechnological horizons in diagnosis of multiple diseases. In recent years, many researches have been focused on developing novel and effective tau protein biosensors for rapid and accurate detection of AD. In this review, tau protein function and correlation with AD as well as the eminent research on developing nanobiosensor based on optical, electrochemical and piezoelectric approaches will be highlighted.

Cognitive deficits due to spinal cord injury (SCI) have been elucidated in both animals and humans with SCI. Such disorders may cause concomitant oscillatory changes in regions of the brain involving in cognition; a subject that has not been directed mechanistically. One of the crucial oscillations, having a prominent role in cognition, particularly spatial memory, is hippocampal theta rhythm. Our research revealed that SCI could induce changes not only in the neurogenesis and apoptosis rate of the hippocampus but also in theta power as well as receptors involving in the generation of this rhythm. Herein we used 24 male Wistar rats (Sham/SCI = 12) and examined the effect of spinal cord contusion on hippocampal theta rhythm, spatial memory, and neurodegeneration. We proved that SCI eliminates hippocampus-dependent theta power through spatial working memory, and correlates significantly with neurodegeneration and expression of receptors (NMDA, GABAA, Muscarinic1/M1), which are in turn essential in generation of theta rhythm. The immunohistochemistry analysis also demonstrated a significant decrease in DCX+ and BrdU+ cells; however, according to TUNEL assay, apoptosis is significantly higher in SCI-induced animals. The western blotting analysis further showed a significant reduction of the abovementioned receptors in the hippocampus. We also verified that SCI impairs the spatial memory, proved by poor performance in the Y-maze task. As well as, based on the local field potential recordings analysis, SCI decreases the power of theta rhythm. Eventually, this study demonstrated that chronic brain neurodegeneration occurs after SCI accompanied by theta rhythm and cognitive deficiency.

The integrity of the structural cerebral cortex is disrupted after stroke either at the macroscopic or microscopic levels. Therefore, many attempts have been gathered to circumvent stroke-associated problems in the brain tissue. The current study was aimed to design an animal model of photochemical stroke using rose bengal (RB) plus laser irradiation (L) after 10, 15, and 20 min (´) and evaluate its effect on the cerebral tissue using unbiased stereological quantitative methods and morphometric histological analysis. Photochemical stroke was induced by intraperitoneal injection of RB dye and further activation through the exposure of the right sensorimotor cortex with the green laser radiation (100 mW; 532 nm). Mice were randomly allocated into 4 groups (each in 15) as follows: control (10 μg/gbw RB), RB + 10’L, RB + 15’L, and RB + 20’L. Target irradiation site was adjusted to 2 mm lateral to the bregma. Vernier caliper morphometric evaluation, cresyl violet staining, and unbiased stereological assays including Cavalier’s principle and point counting techniques were used to monitor the pathological changes and lesion volume on days 1, 3, and 7 after the ischemia induction. Our data showed that the mean diameter of the lesion site and lesion infarct volume in the group RB + 20’L) was significantly increased relative to the other groups (P

During the last decades, numerous basic and clinical studies have been conducted to assess the delivery efficiency of therapeutic agents into the brain and spinal cord parenchyma using several administration routes. Among conventional and in-progress administrative routes, the eligibility of stem cells, viral vectors, and biomaterial systems have been shown in the delivery of NTFs. Despite these manifold advances, the close association between the delivery system and regeneration outcome remains unclear. Herein, we aimed to discuss recent progress in the delivery of these factors and the pros and cons related to each modality.

Direct astrocyte reprogramming to neural progenitor cells and promotion of neurogenesis is considered as an alternative approach to replace the lost neurons in the spinal cord injury(SCI). Herein, we used the human amniotic fluid mesenchymal stem cells (hAF-MSCs) and their conditioned medium (CM), to investigating their ability to reprogramming astrocytes to neuroblasts following SCI. 54 adult rats were randomly divided into 9 groups (n = 6), included: Control, SCI, (SCI + DMEM), (SCI + CM), (SCI + MSCs), (SCI + Astrocyte), (SCI + Astrocyte + DMEM), (SCI + Astrocyte + CM) and SCI + Astrocyte + MSCs). Following laminectomy and SCI induction, DMEM, CM, MSCs and Astrocytes were injected. Wester-blot was performed to explore the levels of the Sox2 protein in the MSCs-CM. The immunofluorescence staining against DCX and GFAP was done. Finally, Basso-Beattie-Brenham (BBB) locomotor test was conducted to assess the neurological outcomes. Our results showed that the MSCs through juxtacrine and paracrine mechanisms induced the promotion of the endogenous neuroblasts and the decline of astrocytes. Moreover, in the present research, MSCs and CM could convert the transplanted human astrocytes to neuroblasts in the spinal cord injury. Taken together, our data indicate the MSCs via juxtacrine and paracrine pathways could direct the spinal cord endogenous neural stem cells(NSCs) to the neuroblasts lineage rather than astrocytes as well as induce reprogramming. Ultimately, MSCs could reverse the neurobehavioral deficit in the SCI. The striking output in our study was the capability of the MSCs in the reprogramming of the astrocytes to neuroblasts via juxtacrine and paracrine pathways in the In-vivo condition.

One of the most important natural extracellular constituents is hyaluronic acid (HA) with the potential to develop a highly organized microenvironment. In the present study, we enriched HA hydrogel with tenascin-C (TN-C) and examined the viability and survival of mouse neural stem cells (NSCs) using different biological assays. Following NSCs isolation and expansion, their phenotype was identified using flow cytometry analysis. Cell survival was measured using MTT assay and DAPI staining after exposure to various concentrations of 50, 100, 200, and 400 nM TN-C. Using acridine orange/ethidium bromide staining, we measured the number of live and necrotic cells after exposure to the combination of HA and TN-C. MTT assay revealed the highest NSCs viability rate in the group exposed to 100 nM TN-C compared to other groups, and a combination of 1% HA + 100 nM TN-C increased the viability of NSCs compared to the HA group after 24 hours. Electron scanning microscopy revealed the higher attachment of these cells to the HA + 100 nM TN-C substrate relative to the HA substrate. Epifluorescence imaging and DAPI staining of loaded cells on HA + 100 nM TN-C substrate significantly increased the number of NSCs per field over 72 hours compared to the HA group ( P < 0.05). Live and dead assay revealed that the number of live NSCs significantly increased in the HA + 100 TN-C group compared to HA and control groups. The enrichment of HA substrate with TN-C promoted viability and survival of NSCs and could be applied in neural tissue engineering approaches and regenerative medicine.

Background: Photothrombotic (PT) stroke model is a reliable, reproducible, noninvasive and accessible method to induce ischemic stroke in the target site using excitation of photosensitive agents such as Rose Bengal (RB) dye after light illumination. Methods: The thirty animals were assigned into three groups of Laser irradiation, RB, and Laser irradiation+RB. We assessed ischemic stroke outcomes through multiple cellular and behavioral approaches. Laser irradiation+ RB promoted pale ischemic changes after 7 days. Microscopic staining revealed neural tissue degeneration and demarcated necrotic site and neuronal injury plus prominent astrogliosis in the periphery of irradiated sites. We performed (BrdU/NeuN) staining to examine the neurogenesis on day 28. The volume of the lesion site was calculated using unbiased stereological study and Cavalier’s principle. To assess the efficiency of ischemic stroke, modified neurological severity score (mNSS) and cylinder tests were done on days 1, 7, 14, and 28. Results: BrdU+/NeuN+ staining showed a significant increase in the number of proliferating cells in the Laser irradiation+ RB group compared to the other groups (pConclusion: Our study revealed that the PT although increased the cell proliferating in the periphery of the lesion site, but due to an undesirable microenvironment, the neurogenesis decreased concomitantly with the functional and infarct size alleviation.

The COVID-19 pandemic has profoundly influenced public health and contributed to global economic divergences of unprecedented dimensions. Due to the high prevalence and mortality rates, it is then expected that the consequence and public health challenges will last for long periods. The rapid global spread of COVID-19 and lack of enough data regarding the virus pathogenicity multiplies the complexity and forced governments to react quickly against this pandemic. Stem cells represent a small fraction of cells located in different tissues. These cells play a critical role in the regeneration and restoration of injured sites. Because of their specific niche and a limited number of stem cells, the key question is whether there are different anti-viral mechanisms against viral infection notably COVID-19. Here, we aimed to highlight the intrinsic antiviral resistance in different stem cells against viral infection. These data could help us to understand the possible viral infections in different stem cells and the activation of specific molecular mechanisms upon viral entrance., Tabriz University of Medical Sciences

Herein, we investigated the effect of electrospun polycaprolactone fumarate (PCLF) nanofibers on neural stem cell (NSC) behavior in the in vitro setting. Murine NSCs were isolated from adult mice subventricular zone and immunophenotyped by flow cytometry assay and immunofluorescence staining. Cells were cultured on the plastic surface, laminin-coated surface, and electrospun PCLF nanofibers. Cell morphology, attachment, and spreading were evaluated by scanning electron microscopy analysis. Cell viability and proliferation rates were evaluated by MTT assay. The proliferation of plated cells was investigated by monitoring Ki-67-positive cells using flow cytometry analysis. The protein levels of Map-2 and GFAP were detected by using immunofluorescence staining to show neural and astrocyte differentiation capacity. Scanning electron microscopy images revealed an extensive distribution, morphological adaptation, and cell-to-cell connectivity in NSCs upon culture on the PCLF surface. MTT analysis showed that the NSCs had more survival rates on the PCLF surface compared to the laminin and control groups over time (p < 0.05). In contrast to the laminin group, Ki-67 analysis showed a decrease of proliferating cells in the PCLF group. Immunofluorescence staining revealed the prominent increase of Map-2 and GFAP reduction in NSCs from the PCLF group compared to the laminin and control groups, showing the stimulatory effect of PCLF on targeted maturation of NSCs (p < 0.05). In brief, PCLF based construct promotes NSCs morphological adaptation and neuronal differentiation, suggesting PCLF as an appropriate and applicable substrate in neural tissue engineering.

Purpose: Application of Mummy material for treatment of different diseases such as bone fracture, cutaneous wounds and joint inflammation has been advised since hundred years ago in Persian traditional medicine. Due to the claims of indigenous people and advice of traditional medicine for application of this material in healing of bone fractures, this study has been designed to evaluate whether Mummy material can promote the differentiation of mesenchymal stem cells into osteoblasts and enhance the expression of bone specific genes and proteins. Methods: Adipose derived stem cells (ASCs) at fourth cell passage were divided into control, osteogenesis group (received osteogenic medium), Mummy group (received Mummy at concentration of 500 µg/ml). ASCs in the fourth group were treated with both osteogenic medium and Mummy (500µg/ml). Cells in all groups were harvested on days 7, 14 and 21 days for further evaluation through Real time RT-PCR, Von kossa staining, Immunocytochemistry and flowcytometery. Results: Treatment of ASCs with Mummy at concentration of 500µg/ml promotes the expression level of Osteocalcin, RUNX-2 and β1-integrin genes in different time points but that of the Osterix did not changed. Furthermore the expression of Osteocalcin protein enhanced significantly in ASCs treated with Mummy detected by Immunocytochemistry and flowcytometery technique compared to the control groups. The results of this study also showed that treatment of ASCs with Mummy resulted in formation of mineral deposits which was evaluated by Von Kossa staining method. Conclusion: Obtained data from this study reveals that Mummy is a potent enhancer for differentiation of ASCs into osteoblasts in in vitro system, probably through increasing the level of bone specific genes and proteins.

Parkinson’s disease (PD) is the second most common neurodegenerative disorder and is characterized by a spectrum of clinicopathologic signs and a complex etiology. PD results from the degeneration of dopaminergic (DAergic) neurons in the substantia nigra. Current therapies for PD are only able to alleviate symptoms without stopping disease progression. In addition, the available therapeutic strategies do not have long-lasting effects. Furthermore, these therapies cause different ranges of adverse side effects. There is great interest in neurotrophic factors (NTFs) due to their ability to promote the survival of different neural cells. These factors are divided into four families: neurotrophins, neurokines, the glial cell line-derived NTF family of ligands, and the newly recognized cerebral DA NTF/mesencephalic astrocyte-derived NTF family. The protective and therapeutic effects of these factors on DAergic neurons make them suitable for the prevention of progressive cell loss in PD. Based on the above premise, we focus on the protective effects of NTFs, especially CDNF and MANF, on nigrostriatal DAergic neurons in PD.

Spinal cord injury (SCI) is a debilitating condition within the neural system which is clinically manifested by sensory-motor dysfunction, leading, in some cases, to neural paralysis for the rest of the patient’s life. In the current study, mesenchymal stem cells (MSCs) were isolated from the human amniotic fluid, in order to study their juxtacrine and paracrine activities. Flow cytometry analysis was performed to identify the MSCs. A conditioned medium (CM) was collected to measure the level of BDNF, IL-1β, and IL-6 proteins using the ELISA assay. Following the SCI induction, MSCs and CM were injected into the lesion site, and also CM was infused intraperitoneally in the different groups. Two weeks after SCI induction, the spinal cord samples were examined to evaluate the expression of the doublecortin (DCX) and glial fibrillary acid protein (GFAP) markers using immunofluorescence staining. The MSCs’ phenotype was confirmed upon the expression and un-expression of the related CD markers. Our results show that MSCs increased the expression level of the DCX and decreased the level of the GFAP relative to the injury group (p &lt, 0.001). Additionally, the CM promoted the DCX expression rate (p &lt, 0.001) and decreased the GFAP expression rate (p &lt, 0.01) as compared with the injury group. Noteworthily, the restorative potential of the MSCs was higher than that of the CM (p &lt, 0.01). Large-scale meta-analysis of transcriptomic data highlighted PAK5, ST8SIA3, and NRXN1 as positively coexpressed genes with DCX. These genes are involved in neuroactive ligand–receptor interaction. Overall, our data revealed that both therapeutic interventions could promote the regeneration and restoration of the damaged neural tissue by increasing the rate of neuroblasts and decreasing the astrocytes.

Natural killer (NK) cells have significant capability in tumor immune-surveillance. The ability of lyse transformed cells immediately in an antigen-independent manner make them an attractive candidate for cancer cell therapy. Despite employment of NK cells in cancer immunotherapy, clinical trials are faced with serious limitations such as trouble with the penetration of NK cells in tumor sites, limited in vivo persistence, and tumor microenvironment interference. Taken together, the NK-cell cancer therapy is still infant scenario that has a long way to be translated in clinic. Current article first reviews characteristic features of NK lymphocytes. Then, it discusses about important disruptive barriers and motivator in the developmental stages of NK cells like as tumor microenvironment. Finally, some revolutionary approaches are highlighted utilizing of NK cells in cancer therapy.

Acute lymphoblastic leukemia (ALL) is an aggressive cancer in children and adults which possess higher CD47 expression than normal cells. ALL chemotherapy has a lot of side effects and in most cases is ineffective. However arrival of Natural killer (NK) cell immunotherapy raised hopes for successful treatment of cancers, tailoring NK cells to meet clinical requirements is still under investigation. Of note, CD16+ (FCγIIIa) NK cells eliminate tumor cells with antibody dependent cell cytotoxicity (ADCC) mechanism. Therefore, we evaluated ADCC effect of cord blood stem cell derived CD16+ NK cells with using anti CD47 blocking antibody. CD16+ NK cells generated efficiently from CD34 positive cord blood cells in vitro using IL-2, IL-15 and IL-21 cytokines, although it was not dose dependent. CD16+ cells derived from CD34+ cells in day 14 of culture efficiently increased apoptosis in ALL cells, produced INFγ and increased CD107-a expression when used anti CD47 antibody (increased around 30-40%). Interestingly, CD16+ NK cell cytotoxicity slightly increased in combination with macrophages against ALL cells (around 10%). Taken together, our findings induced this hope that cord blood stem cell derived CD16+ NK cells exploit antitumor immune response in cancer therapy with using anti-CD47 antibody.

Background The brain development during the prenatal period is affected by various factors, including the mother's metabolic condition. It has been revealed that diabetes in pregnancy is associated with structural and functional alterations in offspring’s hippocampus. Hippocampus, as a critical region with well-known roles in learning and memory consolidation, is vulnerable to changes in glucose level. This study was designed to investigate the effects of maternal diabetes during the pregnancy period and insulin therapy on the neuronal density and the volume of different subfields of the hippocampus in rat offspring at postnatal day 14 (P14). Methods Wistar female rats were randomly divided into diabetics (STZ-D), diabetes treated with insulin (STZ-INS) group, and controls (CON). The animals in all groups were mated by non-diabetic male rats. Two weeks after birth, male pups from each group were sacrificed. The Cavalieri method was carried out to estimate the total volume, and the numerical density of the neurons in the hippocampus and its sub regions was measured by the optical dissector technique. Results Bilateral hippocampal volume decreased in the diabetic group, mainly in the CA1, dentate gyrus (DG) and subiculum areas (P ≤ 0.05), when compared to control and insulin-treated diabetic animals. In all hippocampus sub-regions, maternal diabetes resulted in a significant decrease in the number of cells in comparison with two other groups (P ≤ 0.05 each). Conclusion These data indicate that diabetes during pregnancy has a negative impact on the development of the hippocampus in the rats. These changes in the volume of hippocampal CA1, DG, and subiculum areas might be at the core of underlying neurocognitive and neurobehavioral impairments observed in the children of diabetic mothers.

Background: Dementia as a major cognitive neurological disorder is defined as impairment in one or more cognitive territories compared with the former level of performance. This disorder disrupts patient's independence, and the patient would need others aid in order of doing daily and complex activities. The aim of this study was to evaluate the efficacy of Rosa damascena extract in the improvement of cognitive function in patients with dementia. Methods: This study is a randomized double-blind, placebo-controlled clinical trial on 40 patients older than 55 years with dementia referred to Specialized Elderly Patients Clinic in 2015–2016. Patients were divided randomly into two groups (control and intervention). The intervention group used donepezil and R. damascena capsules, and in control group, placebo capsule instead of R. damascena added on donepezil. Four test was filled three times at the study initiation, after month one and also after month three: Mini–Mental State Examination (MMSE) and Addenbrooke's Cognitive Examination Revised (ACE-R) were used for cognition evaluation, for depression assessment, Geriatric Depression Scale was administered, and checklist of memory and behavioral disorders were filled. Results: The results showed add-on donepezil and R. damascena versus placebo improved cognitive impairment based on MMSE with P = 0.002, ACE-R with total P = 0.001, depression (P = 0.012), behavioral disorders (P < 0.001), and daily activity (P < 0.001). Conclusions: The R. damascena extract affected cognitive impairment of dementia patients significantly and also have significant effects on improving depression and behavioral problems.

Objective: For a long time there was a central dogma that new neurons are not generated in the adult mammalian brain. But nowadays, it is well accepted that new neurons are continuously generated in discrete neurogenic regions of the brain throughout adult life. Neurological disorders are characterized by neuronal cell death, glial scar formation, axonal damage and deterioration of the cerebral cytoarchitecture and neuronal circuitry which result in functional deficits. Since the promising strategy for regenerating the damaged central nervous system (CNS), is the activation and recruitment of the endogenous regenerative capacity, therefore we investigated the neurogenesis potential of endogenous neural stem cells in an adult mouse brain. Methods and Materials : Since the some documented experimental studies have shown that the long-term injection of the BrdU induces cell senescence and astroglial differentiation, in the present study, BrdU intraperitoneal injection was applied in a short period of time. The number of animals sacrificed for evaluation of the proliferation of neural stem and progenitor cells and 4 weeks following the last BrdU injection, the rest of the animals was used for investigation of adult neurogenesis. Results : Findings showed that the neural stem and progenitor cells produce in the subgranular zone (SGZ) of the dentate gyrus and after 4 weeks differentiate into mature neurons. Also, this experiment showed that the possibility of the evaluation of adult neurogenesis mechanism will be provided with BrdU injection in a short time. Conclusion : The generation and integration of new neurons is a continuous physiological process that occurs in the brain. Therefore, the use of endogenous neural stem cells is a promising approach for neural tissue regeneration in the neurological conditions.

The number of older people who are suffering from memory impairment is increasing among populations throughout the world. Alzheimer's disease (AD) affects about 5% of people over 65 years old. The hippocampus, a brain area critical for learning and memory, is especially vulnerable to damage in the early stages of AD. Emerging evidence suggests that loss of neurons and synapses are correlated with dementia in this devastating disease. Therefore, neurogenesis and synaptogenesis in adulthood could serve as a preventive as well as a therapeutic target for AD. This study investigated the effect of Rosa damascena extract on neurogenesis and synaptogenesis in an animal model of AD. Molecular, cellular, and behavioral experiments revealed that this treatment could induce neurogenesis and synaptic plasticity and improve memory in AD. Our study suggests that R. damascena is a promising treatment for mild memory impairments and AD.

Background: Alzheimer's disease (AD) is an age-related progressive neurodegenerative disease, which is characterized clinically by serious impairment in memory and cognition. Current medications only slow down the dementia progression and the present treatment one-drug one-target paradigm for anti-AD treatment appears to be clinically unsuccessful. Therefore, alternative therapeutic strategies are urgently needed. With respect to multifunctional and multitargeted characteristics of Rosa damascena via its effective flavonoids, we investigated the effects of R. damascena extract on behavioral functions in a rat model of amyloid-β (A-β)-induced Alzheimer's disease. Materials and Methods: After preparation of the methanolic extract of the R. damascena, HPLC analysis and toxicity studies, median lethal dose (LD50) and dose levels were determined. For evaluation of baseline training behavioral performance, Morris water maze and passive avoidance tests were used. A-β was injected bilaterally into CA1 area of the hippocampus. Twenty-one days after injection of A-β, the first probe trial of the behavioral tests were used to confirm learning and memory impairment. To examine the potential effects of the extract on behavioral tasks, the second probe trials were performed after one month administration of R. damasena extract. Results: Results showed that the R. damascena extract significantly improved the spatial and long-term memories in the extract- treated groups in a dose-dependent manner, as in the middle and high doses it had significant effect. Conclusion: According to these results, we concluded that R. damascena can reverse behavioral deficits caused by A-β, and may provide a new potential option for prevention and treatment of the cognitive dysfunction in Alzheimer's disease.