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[Display omitted] • Transplantation of DPSCs improved motor skills and muscle activity in rat brain lesion. • Transplantation of DPSCs prevented the atrophy of the striatum. • Transplantation of DPSCs impeded gliosis and microgliosis in rats. • Transplantation of DPSC downregulated Caspase-3 in brain lesion. • Transplantation of DPSCs decreased the expression of inflammatory cytokines, TNF and IL-1β, at mRNA level. Stem cell-based therapy has recently offered a promising alternative for the remedy of neurodegenerative disorders like Huntington's disease (HD). Herein, we investigated the potential ameliorative effects of implantation of dental pulp stem cells (DPSCs) in 3-nitropropionic acid (3-NP) rat models of HD. In this regard, human DPSCs were isolated, culture-expanded and implanted in rats lesioned with 3-NP. Post-transplantation examinations revealed that DPSCs were able to survive and augment motor skills and muscle activity. Histological analysis showed DPSCs treatment hampered the shrinkage of the striatum along with the inhibition of gliosis and microgliosis in the striatum of 3-NP rat models. We also detected the downregulation of Caspase-3 and pro-inflammatory cytokines such as TNF and IL-1β upon DPSCs grafting. Overall, these findings imply that the grafting of DPSCs could repair motor-skill impairment and induce neurogenesis, probably through the secretion of neurotrophic factors and the modulation of neuroinflammatory response in HD animal models. [ABSTRACT FROM AUTHOR]

Tramadol is a centrally acting synthetic opioid analgesic and SNRI (serotonin/norepinephrine reuptake-inhibitor) that structurally resembles codeine and morphine. Given the tramadol neurotoxic effect and the body of studies on the effect of tramadol on the cerebellum, this study aims to provide deeper insights into molecular and histological alterations in the cerebellar cortex related to tramadol administration. In this study, twenty-four adult male albino rats were randomly and equally divided into two groups: control and tramadol groups. The tramadol group received 50 mg/kg of tramadol daily for 3 weeks via oral gavage. The functional and structural change of the cerebellum under chronic exposure of tramadol were measured. Our data revealed that treating rats with tramadol not only lead to cerebellum atrophy but also resulted in the actuation of microgliosis, neuroinflammatoin, and apoptotic biomarkers. Our results illustrated a significant drop in VEGF (vascular endothelial growth factor) level in the tramadol group. Additionally, tramadol impaired motor coordination and neuromuscular activity. We also identified several signaling cascades chiefly related to neurodegenerative disease and energy metabolism that considerably deregulated in the cerebellum of tramadol-treated rats. Overall, the outcomes of this study suggest that tramadol administration has a neurodegeneration effect on the cerebellar cortex via several pathways consisting of microgliosis, apoptosis, necroptosis, and neuroinflammatoin. [ABSTRACT FROM AUTHOR]

Tramadol is a synthetic analogue of codeine that is often prescribed for the treatment of mild to moderate pains. It has a number of side effects including emotional instability and anxiety. In this study, we focus on the structural and functional changes of prefrontal cortex under chronic exposure to tramadol. At the cellular level, the amounts of ROS and annexin V in PC12 cells were evidently increased upon exposure to tramadol (at a concentration of 600 μM for 48 h). To this end, the rats were daily treated with tramadol at doses of 50 mg/kg for 3 weeks. Our findings reveal that tramadol provokes atrophy and apoptosis by the induction of apoptotic markers such as Caspase 3 and 8, pro-inflammatory markers, and downregulation of GDNF. Moreover, it triggers microgliosis and astrogliosis along with neuronal death in the prefrontal cortex. Behavioral disturbance and cognitive impairment are other side effects of tramadol. Overall, our results indicate tramadol-induced neurodegeneration in the prefrontal cortex mainly through activation of neuroinflammatory response. [ABSTRACT FROM AUTHOR]

Cerebellar ataxias (CA) include a range of neurodegenerative disorders hallmarked by deterioration of the cerebellum. Cell replacement therapy (CRT) offers a potential remedy for the diseases associated with the central nervous system (CNS). This study was designed to assess the neurorestorative/protective effects of dental pulp stem cell (DPSC) implantation on a rat model of CA induced by 3-acetylpyridine (3-AP) as a neurotoxin. To begin, human DPSCs were extracted, cultured and phenotypically characterized. Then, experimental ataxia was induced in 20 male adult rats by a single injection of 3-AP and bilateral DPSC transplantation was performed 3 days after 3-AP administration, followed by stereological analysis of cerebellar layers along with assessment of motor skills and inflammatory response. The findings showed that transplantation of DPSCs in a 3-AP model of ataxia ameliorated motor coordination and muscle activity, increased cerebellar volumes of molecular and granular layers plus white matter, reduced the levels of inflammatory cytokines and thwarted the degeneration of Purkinje cells against 3-AP toxicity. Taken together, human DPSCs could be considered as a suitable candidate for CRT-based therapies with a specific focus on CA. [ABSTRACT FROM AUTHOR]

Neural differentiation involves drastic morphological alterations, essentially performed by a cell‐homeostasis maintaining process known as autophagy. Here, we used the cocktail of choroid plexus epithelial cell‐conditioned medium (CPEC‐CM) and 15% knockout serum (KS) to induce human adipose‐derived mesenchymal stem cells (hASCs) into tyrosine hydroxylase (TH)‐positive neuron like cells. We showed that upon this induction, autophagy pathway was transcriptionally triggered. The expression levels of autophagy markers mTOR, BECN1, and MAP1LC3 were evidently changed throughout the dopaminergic (DAergic) differentiation of hASCs, highlighting the critical role of autophagy in this process at the level of transcription. [ABSTRACT FROM AUTHOR]

Human adipose-derived stem cells (hADSCs) have great capacity to differentiate into mesodermal origins as well as nonmesodermal lineages, including neural cells. This valuable feature paves the way for the therapeutic application of hADSCs for neurodegenerative maladies such as Parkinson's disease (PD). We tested the capacity of choroid plexus epithelial cell-conditioned medium (CPEC-CM) alone or cocktailed with knockout serum (KS) to induce dopaminergic (DAergic) differentiation of hADSCs. To this end, hADSCs from lipoaspirate were phenotypically characterized and shown to maintain mesodermal multipotency so that selected media easily differentiated them into osteoblasts, chondrocytes, and adipocytes. To begin inducing hADSC neuronal differentiation, we isolated CPECs from rat brain and expanded them in culture to obtain CPEC-CM. We then treated hADSCs with optimized quantities of collected CPEC-CM, KS, or both. The ADSCs treated with either CPEC-CM or CPEC-CM and KS displayed morphological changes typical of neuron-like phenotypes. As revealed by reverse transcription polymerase chain reaction (RT-PCR), quantitative real-time PCR (qPCR), and immunostaining analyses, hADSCs cotreated with CPEC-CM and KS expressed significantly higher levels of neuronal and DAergic markers in comparison with single-treated groups. Moreover, the hADSCs began expressing dopamine-biosynthesizing enzymes mainly after cotreatment with CPEC-CM and KS. Consequently, only cotreated hADSCs were capable of synthesizing and releasing dopamine detectable by high-performance liquid chromatography (HPLC). Finally, hADSCs growing in an ordinary medium were found positive for astrocytic marker glial fibrillary acidic protein (GFAP), but stopped GFAP expression on either single or cotreatments. These combined results suggest that CPEC-CM and KS can synergize to remarkably augment DAergic induction of hADSCs, an effect that has implications for cell replacement therapy for PD and related disorders. [ABSTRACT FROM AUTHOR]

• Transplantation of OE-MSCs provokes overexpression of DAergic markers in the striatum of PD models. • Grafting of OE-MSCs improves motor coordination and muscle activity in 6-OHDA model of PD. • OE-MSCs implantation ameliorates locomotor performance in PD rat models. One of the complex neurodegenerative disorders is Parkinson disease (PD). PD is mainly caused by dopaminergic (DAergic) neuron degeneration in the midbrain. The loss of DAergic neurons is considered as a key reason of motor functional defects in PD patients. Cell replacement strategies are considered as an alternative remedy to effectively address neurodegeneration in PD. In this report, we evaluated the restorative effect of human olfactory ecto-mesenchymal stem cells (OE-MSCs) in rat models of PD. Accordingly, human OE-MSCs were isolated and phenotypically characterized by flow cytometry and immunocytochemistry. Next, the undifferentiated OE-MSCs were unilaterally transplanted into the striatum of 6-hydroxydopamine (6-OHDA)-lesioned rat models, followed by molecular and histological analyzes as well as assessment of motor skills. Our results displayed that the grafting of OE-MSCs increased the expression of DAergic markers namely dopamine transporter (DAT), tyrosine hydroxylase (TH), nuclear receptor related-1 (Nurr1) in a 6-OHDA model compared with that of control, detected by immunohistochemical staining and western blot. Moreover, noticeable improvements in motor coordination, muscle activity and locomotor performance were observed in 6-OHDA model of PD following OE-MSCs transplantation. Taken together, our finding indicates that undifferentiated OE-MSCs might be counted as an appropriate source for cell replacement therapy particularly aimed at PD. [ABSTRACT FROM AUTHOR]

• METH injection induced considerable impairment in motor coordination and muscle activities. • METH provoked astrocyte over-activation (astogliosis) in the striatum. • METH exacerbated the striatal atrophy. • MiRNA sequencing analysis identified 167 differentially expressed miRNAs in the striatum under METH treatment. • The pathway enrichment analysis revealed remarkably enriched pathways mainly involved in cell apoptosis, growth and synaptic plasticity Methamphetamine (METH) is a high addictive psychostimulant drug which triggers brain atrophy via neuronal degeneration. Striatum is the main part of the brain that is regarded as a key target for drug-induced damages. MiRNAs as small regulatory molecules at the post-transcriptional level play a major role in biological pathways. In this study, initially we performed behavioral assessment in METH-treated rats. Then, we examined striatal volume and dendritic length, and also the levels of tyrosine hydroxylase (TH), caspase-3 and glial fibrillary acidic protein (GFAP) were immunohistochemically assessed. Moreover, we investigated miRNA expression profiling using high-throughput small RNA-seq technology. Based on our data, METH provoked declined motor coordination, decreases in striatal volume and dendritic length along with over-activation of astrogliosis. In addition, METH treatment down-regulated TH level while it induced up-regulation of caspase-3 in the striatal region. Furthermore, according to miR-seq analysis, we found 167 deregulated miRNAs in the striatum upon METH treatment, that among them rno-let-7b-5p, rno-miR-485-5p, rno-miR-326-3p, rno-miR-34a-5p, rno-miR-3068-5p showed high miRNA-target gene interaction. Pathway analysis revealed that miRNAs and their target genes may be involved in cell apoptosis, growth, differentiation as well as synaptic plasticity associated pathways. Altogether, we can conclude that METH noticeably elicited neuro-degeneration in the dorsal striatum. [ABSTRACT FROM AUTHOR]

• Tramadol upregulated expression of some of the autophagy and apoptosis. markers genes in tramadol-treated cultured PC12 cells. • Tramadol administration led to increase of inflammatory and apoptotic markers. • Tramadol treatment led to the shrinkage of striatum. Tramadol is a synthetic analogue of codeine, mostly prescribed for the alleviation of mild to moderate pains. It bears several side effects including emotional instability and anxiety. In this study, we focused on the alteration in expression of autophagic and apoptotic genes in PC-12 cells for our in vitro and structural and functional changes of striatum for our in vivo under chronic exposure of tramadol. For in vitro side of the study, PC12 cells were exposed to tramadol (50 μM) and expression of apoptosis and autophagy genes were determined. In parallel, rats were daily treated with tramadol at doses of 50 mg/kg for three weeks for the in vivo side. Motor coordination, EMG, histopathology and gene expression were done. Our in vitro findings revealed that tramadol increased expression of apoptosis and autophagy genes in PC12 cells. Moreover, our in vivo results disclosed that tramadol not only provoked atrophy of rats' striatum, but also triggered microgliosis along with neuronal death in the striatum. Tramadol also reduced motor coordination and muscular activity. Altogether, our data indicated that tramadol induced neurotoxicity in the PC12 cells via apoptosis and autophagy and in striatum chiefly through activation of neuroinflammatory and apoptotic responses. [ABSTRACT FROM AUTHOR]

• METH administration interrupts spatial memory and long term potentiation (LTP). • Stereological analysis revealed a significant alteration in hippocampal volume. • Injection of METH induced astrogliosis in the hippocampus. • Several signaling cascades were interrupted in hippocampus of METH-treated rats. Methamphetamine (METH) is a strong psychostimulant drug which can essentially affect different brain regions. Hippocampus as one of main components of limbic system plays key roles in processing of short term, long term and spatial memory. Herein, we explored the changes in behavior, synaptic transmission and hippocampal volume along with gliosis following METH treatment. Besides, using genome-wide expression profiling, we applied a pathway-based approach to detect significantly dysregulated signaling pathways. In this regard, we found that METH administration interrupts spatial memory and long term potentiation (LTP). Additionally, stereological analysis revealed a significant alteration in hippocampal volume along with increased gliosis upon METH treatment. We also identified several signaling cascades chiefly related to synaptic transmission which were considerably interrupted in the hippocampus of METH-treated rats. Taken together, our data suggests a potential link between behavioral disruptions and dysregulated signaling pathways. [ABSTRACT FROM AUTHOR]

• METH triggers differential gene expression in apoptosis, autophagy and inflammation pathways. • METH treatment exacerbated neuronal degeneration in PFC. • METH administration remarkably provoked gliosis in PFC. • Neurotrophic factor BDNF is dysregulated upon the influence of METH. Damage to the reward brain system is regarded as a key consequence of narcotic drug abuse, including methamphetamine (METH). The Prefrontal cortex (PFC) is one of the brain areas associated with mesocortical pathway, which plays principal roles in cognitive behavior and memory function. In spite of the potential role of PFC in METH abuse, little is known about METH-induced neurotoxicity in PFC region. In this study, we examined neurotoxicity–associated molecular pathways such as inflammation, apoptosis and autophagy in PFC under the influence of METH using quantitative real time PCR (qPCR). Besides, the protein levels of brain derived neurotrophic factor (BDNF) and glial fibrillary acidic protein (GFAP) as markers of synaptic plasticity and gliosis were inspected, respectively. Then we performed stereological analysis in METH-treated rats. Based on our findings, qPCR analysis revealed impaired autophagy, increased apoptosis and inflammation along with histological alterations in PFC, augmented astrogliosis as well as a significant reduction in the level of BDNF. Collectively, our molecular and histological data imply that METH administration in PFC region provoked differential expression changes in neurotoxicity-associated signaling cascades namely inflammation, apoptosis and autophagy coupled with significant PFC atrophy. [ABSTRACT FROM AUTHOR]

Highlights • Grafted Sertoli cells (SCs) exhibited a decline in apoptosis in a rat model of amyloid beta toxicity. • Implantation of SCs in rats with Aβ1-42 receiving vehicle decreased the amount of gliosis. • We found that implanted SCs can recover hippocampus dependent memory and learning. • Transplanted SCs restored long-term synaptic plasticity in lesioned rats. Abstract Alzheimer's disease (AD) is a degenerative nerve disease which adversely affects memory and learning skills. Currently, there is no disease-modifying therapeutic approach for AD. However, a growing body of literature suggests cell based therapies as a promising remedy for neurological disorders. Among the potential cell sources, testis- derived Sertoli cells (SCs) appear to be an attractive choice due to their immune-privileged capacities. Herein, we investigated the neuro-restorative/protective effects of SC transplants in a rat model of amyloid beta toxicity. To this end, GATA-4 and vimentin positive SCs were transplanted into rats with amyloid beta induced hippocampal lesions. According to our in vivo results, implanted SCs survived, exhibited reduction in both apoptosis as well as astrocytic migration. Additionally, transplantation of SCs restored hippocampus dependent memory and learning, along with the recovery of long-term synaptic plasticity. Taken together, these data indicate that SCs are a valuable source for cell-based therapies particularly aimed at AD. [ABSTRACT FROM AUTHOR]

To understand in detail the transcriptional and functional overlap of IFN-I- and IFN-II-activated responses, we used an integrative RNAseq-ChIPseq approach in Huh7.5 cells and characterized the genome-wide role of pSTAT1, pSTAT2, IRF9 and IRF1 in time-dependent ISG expression. For the first time, our results provide detailed insight in the timely steps of IFNα- and IFNγ-induced transcription, in which pSTAT1- and pSTAT2-containing ISGF3 and GAF-like complexes and IRF1 are recruited to individual or combined ISRE and GAS composite sites in a phosphorylation- and time-dependent manner. Interestingly, composite genes displayed a more heterogeneous expression pattern, as compared to GAS (early) and ISRE genes (late), with the time- and phosphorylation-dependent recruitment of GAF, ISGF3 and IRF1 after IFNα stimulation and GAF and IRF1 after IFNγ. Moreover, functional composite genes shared features of GAS and ISRE genes through transcription factor co-binding to closely located sites, and were able to sustain IFN responsiveness in STAT1-, STAT2-, IRF9-, IRF1- and IRF9/IRF1-mutant Huh7.5 cells compared to Wt cells. Thus, the ISRE + GAS composite site acted as a molecular switch, depending on the timely available components and transcription factor complexes. Consequently, STAT1, STAT2 and IRF9 were identified as functional composite genes that are part of a positive feedback loop controlling long-term IFNα and IFNγ responses. More important, in the absence of any one of the components, the positive feedback regulation of the ISGF3 and GAF components appeared to be preserved. Together, these findings provide further insight in the existence of a novel ISRE + GAS composite-dependent intracellular amplifier circuit prolonging ISG expression and controlling cellular responsiveness to different types of IFNs and subsequent antiviral activity. It also offers an explanation for the existing molecular and functional overlap between IFN-I- and IFN-II-activated ISG expression. [ABSTRACT FROM AUTHOR]

Huntington disease (HD) is an inherited disorder hallmarked by progressive deterioration of specific neurons, followed by movement and cognitive anomalies. Cell therapy approaches in neurodegenerative conditions have concentrated on the replenishment of lost/dying neurons with functional ones. Multipotent mesenchymal stem cells (MSCs) have been represented as a potential remedy for HD. In this study, we evaluated the in vitro and in vivo efficacy of umbilical cord matrix stem cells (UCMSCs) and their paracrine effect against oxidative stress with a specific focus on HD. To this end, UCMSCs were isolated, immunophenotypically characterized by the positive expression of MSC markers, and exhibited multilineage potentiality. Besides, synthesis of neurotrophic factors of GDNF and VEGF by UCMSC was confirmed. Initially, PC12 cells were exposed to superoxide in the presence of conditioned media (CM) collected from UCMSC (UCMSC-CM) and cell viability plus neuritogenesis were measured. Next, bilateral striatal transplantation of UCMSC in 3-nitropropionic acid (3-NP) lesioned rat models was conducted, and 1 month later, post-graft analysis was performed. According to our in vitro results, CM of UCMSC protected PC12 cells against oxidative stress and considerably enhanced cell viability and neurite outgrowth. On the other hand, transplanted UCMSC survived, decreased gliosis, and ameliorated motor coordination and muscle activity, along with an increase in striatal volume as well as in dendritic length of the striatum in HD rats. Collectively, our findings imply that UCMSCs provide an enriched platform by largely their paracrine factors, which downgrades the unfavorable effects of oxidative stress. [ABSTRACT FROM AUTHOR]

Photo biomodulation (PBM) as a non-invasive and safe treatment has been demonstrated the anti-inflammatory potential in a variety of cell types, including stem cells. However, further investigations using different laser parameters combined with more accurate methods such as quantitative measurement of inflammatory gene expression at the mRNA level are still necessary. The aim of this study was to evaluate the effect of 532 nm green laser on cell proliferation as well as expression of inflammatory genes in human adipose-derived mesenchymal stem cells (hADMSCs) using RNA sequencing (RNA-seq) technique and confirmatory RT-PCR. hADMSCs were cultured in DMEM low glocuse medium with 10% fetal bovine serum until the fourth passage. Cultured cells were divided in two groups: control group (no laser irradiation) and laser group, irradiated with 532 nm laser at 44 m J/cm2 with an output power of 50 mW and a density of 6 mW/cm2, every other day, 7 s each time. The cell viability was assessed using MTT assay 24 h after each irradiation on days 3, 5, and 7 after cell seeding, followed by performing RNA-seq and RT-PCR. The MTT assay showed that PBM increased cell proliferation on day 5 after irradiation compared to day 3 and decreased on day 7 compared to day 5. In addition, gene expression analysis in hADMSCs using RNA-seq revealed down-regulation of inflammatory genes including CSF2, CXCL2, 3, 5, 6, 8, and CCL2, 7. These results indicate that 532 nm PBM with the parameters used in this study has a time-dependent effect on hADMSCs proliferation as well as anti-inflammatory potential. [ABSTRACT FROM AUTHOR]

• Curcumin enhances motor coordination and Muscle EMG activity in 3-AP treated rats. • Curcumin administration reduces the apoptotic marker of caspase-3 in 3-AP treated rats. • Curcumin boosts total volumes of the cerebellar layers in 3-AP treated rats. • Curcumin enhances the number of Purkinje cells in 3-AP treated rats. Cerebellar ataxias comprise a group of terminal illnesses with ataxia as the main symptom. Curcumin as a yellow polyphenol was extracted from the rhizome of Curcuma longa. Owing to its antioxidant, anti-inflammatory, anti-fibrotic and anti-tumor features, curcumin is considered as a potential therapeutic agent. In this study, we aim to investigate the neuroprotective effects of oral administration of curcumin on a rat model of cerebellar ataxia induced by neurotoxin 3-acetylpyridine. The animals were randomly separated into three groups (control, 3-acetylpyridine, and curcumin + 3-acetylpyridine). Next, motor performance and muscle electromyography activity were assessed. Then, in the molecular part of the study, the anti-apoptotic role of curcumin in cerebellar ataxia and its relationship to protection of Purkinje cells were investigated. Curcumin treatment improved motor coordination and muscular activity, reduced cleaved caspase-3, and increased glutathione level in 3-AP-lesioned rats as well as total volumes of cerebellar granular and molecular layers. the present study implies that curcumin might have neuroprotective effects to counteract neurotoxicity of 3-AP-induced ataxia. [ABSTRACT FROM AUTHOR]

Cerebellar ataxia (CA) is a form of ataxia that adversely affects the cerebellum. Cell replacement therapy (CRT) has been considered as a potential treatment for neurological disorders. In this report, we investigated the neuro-restorative effects of human chorionic stem cells (HCSCs) transplantation on rat model of CA induced by 3-acetylpyridine (3-AP). In this regard, HCSCs were isolated and phenotypically determined. Next, a single injection of 3-AP was administered for ataxia induction, and bilateral HCSCs implantation was conducted 3 days after 3-AP injection, followed by expression analysis of a number of apoptotic, autophagic and inflammatory genes as well as vascular endothelial growth factor (VEGF) level, along with assessment of cerebellar neurodegeneration, motor coordination and muscle activity. The findings revealed that grafting of HCSCs in 3-AP model of ataxia decreased the expression levels of several inflammatory, autophagic and apoptotic genes and provoked the up-regulation of VEGF in the cerebellar region, prevented the degeneration of Purkinje cells caused by 3-AP toxicity and ameliorated motor coordination and muscle function. In conclusion, these data indicate in vivo efficacy of HCSCs in the reestablishment of motor skills and reversal of CA. [ABSTRACT FROM AUTHOR]

Graphical abstract The biopsy of olfactory mucosa could be performed easily and without invasive from adult human. The olfactory ecto-mesenchymal stem cells (OE-MSCs) could be isolated. The OE-MSCs are capable to differentiate to dopaminergic neurons as a promising source of cell therapy for Parkinson's disease. Highlights • The olfactory mucosa could be obtained from adult human easily. • The olfactory mucosa stem cells could differentiate into dopaminergic neuron-like cells. • Olfactory stem cells can be candidate for cell therapy in Parkinson's disease. Abstract The production of dopaminergic (DA) neurons from stem cells holds a great promise for future clinical treatment of neurodegenerative diseases, such as Parkinson's disease (PD). Olfactory ecto-mesenchymal stem cells (OE-MSCs) derived from the adult human olfactory mucosa can be easily isolated and expanded in culture while maintaining their immense plasticity. In addition to reduced ethical concerns, OE-MSCs could be transplanted across allogeneic barriers, making them desirable stem cells for clinical applications. The goal of this study was to define the potentiality of human olfactory mucosa-derived MSCs aimed at differentiation into DA neuron-like cells. OE-MSCs were induced to differentiate to DA neuron-like cells in vitro by using sonic hedgehog (SHH), fibroblast growth factor 8 (FGF8), basic fibroblast growth factor (bFGF), Glial cell line-derived neurotrophic factor (GDNF) and brain derived neurotrophic factor (BDNF). Then the differentiated neurons were characterized for expression of DA neuron markers by Real-time PCR, immunocytochemistry and flow cytometry. Our findings showed that differentiated OE-MSCs could significantly express DA neuron markers at mRNA and protein levels along with dopamine release 12 days post-differentiation. These results support the viability and feasibility of using OE-MSCs as a source of in vitro generated DA neuron-like cells for treatment of DA disorders namely PD. [ABSTRACT FROM AUTHOR]

Methadone is a centrally-acting synthetic opioid analgesic widely used in methadone maintenance therapy (MMT) programs throughout the world. Given its neurotoxic effects, particularly on the hippocampus, this study aims to address the behavioral and histological alterations in the hippocampus associated with methadone administration. To do so, twenty-four adult male albino rats were randomized into two groups, methadone treatment and control. Methadone was administered subcutaneously (2.5–10 mg/kg) once a day for two consecutive weeks. A comparison was drawn with behavioral and structural changes recorded in the control group. The results showed that methadone administration interrupted spatial learning and memory function. Accordingly, treating rats with methadone not only induced cell death but also prompted the actuation of microgliosis, astrogliosis, and apoptotic biomarkers. Furthermore, the results demonstrated that treating rats with methadone decreased the complexity of astrocyte processes and the complexity of microglia processes. These findings suggest that methadone altered the special distribution of neurons. Also, a substantial increase was observed in the expression of TNF-α due to methadone. According to the findings, methadone administration exerts a neurodegenerative effect on the hippocampus via dysregulation of microgliosis, astrogliosis, apoptosis, and neuro-inflammation. • Methadone increased microgliosis and changed some morphological characteristics of microglia cells. • Methadone increased astrogliosis and changed morphological characteristics and distribution of astrocytes cells. • Methadone increased the expression of caspase-3 and TNF-α in the hippocampus. • Methadone decreased the number of neurons and increased the dark neurons in the hippocampus. • Methadone altered the spatial distribution of neurons in the hippocampal granular layer. [ABSTRACT FROM AUTHOR]

• THC administration interrupts long term memory and long term potentiation. • Stereological studies revealed considerable atrophy in hippocampus. • Several signaling cascades related to synaptic regulation were interrupted in hippocampus under THC administration. Tetrahydrocannabinol (THC), a major psychoactive constituent of marijuana, can substantially change the function of several brain areas, leading to behavioral impairment including memory and learning dysfunction. Given the importance of hippocampus as one of the chief parts of the brain involved in memory processing, the present study seeks to investigate structural and histological alterations in hippocampus as well as behavioral defects provoked by THC treatment. Besides, using genome-wide sequencing, we adopted a pathway-based approach to discover dysregulated molecular pathways. Our results demonstrated remarkable hippocampal atrophy, and also interrupted memory function and long term potentiation (LTP) under THC exposure. We also detected several dysregulated signaling pathways involved in synaptic plasticity as well as cell-cell interaction in the hippocampus of THC-treated rats. Overall, the results indicate a potential correlation between disrupted signaling cascades, hippocampal atrophy and memory defects caused by THC treatment. [ABSTRACT FROM AUTHOR]

• MPH blocks dopamine and norepinephrine transporters, resulting in inhibition of the reuptake of these monoamines. • Attention deficit hyperactivity disorder (ADHD) is a kind of neuropsychiatric disorder prevalent nowadays commonly among school-aged children as well as adolescents. ADHD is the most common developmental disorder affecting approximately three to seven percent of school-aged children and 2.5 percent of adults worldwide. The drug of choice for the pharmacotherapy of ADHD is Methylphenidate (MPH). However, there is growing concerns about side effects resulting from its potential interference with brain anatomical and behavioral development. This article focuses on the adverse effects of MPH on the rat's hippocampus. The animals received an oral dose of 5 mg/kg MPH or normal saline, as the vehicle, on a daily basis for 30 days. Y-maze test, passive avoidance, Barnes maze and field potential recording were conducted. Western blot for detecting the neurotrophic factor of GDNF and immunohistochemistry of astrogliosis were performed. Our results revealed that MPH treatment suppressed the willingness of rats to explore new environments. Also, it had no effect on improving long-term potentiation, long-term memory and spatial memory in the MPH group as opposed to the control group. There was also a significant increase of astrogliosis in the treated rats' hippocampi. On the other hand, there was not a significant relationship between MPH administration and the decrement of the GDNF level. We encourage the need to conduct more research on the adverse effects of MPH on the brain. [ABSTRACT FROM AUTHOR]