Implantation of human olfactory ecto-mesenchymal stem cells restores locomotion in a rat model of Parkinson's disease

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. © 2021 Elsevier B.V

Human olfactory stem cells: As a promising source of dopaminergic neuron-like cells for treatment of Parkinson's disease

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. © 201

The role of Tetrahydrocannabinol in inducing disrupted signaling cascades, hippocampal atrophy and memory defects

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. © 2021 Elsevier B.V

Chronic administration of methylphenidate did not affect memory and GDNF levels but increase astrogliosis in adult male rat's hippocampus

Background: 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. Aim: This article focuses on the adverse effects of MPH on the rat's hippocampus. Methods: 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. Results: 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. Conclusion: We encourage the need to conduct more research on the adverse effects of MPH on the brain. © 2020 Elsevier B.V