Secretion Of Neurotrophic Factors Research Articles

Role of MAPK ERK1/2 and p38 in the Regulation of Secretory Functions of Different Populations of Neuroglia in Ethanol-Induced Neurodegeneration.

We studied the participation of ERK1/2 and p38 in secretion of neurotrophic growth factors by various types of neuroglia under conditions of in vitro and in vivo modeled ethanol-induced neurodegeneration. The inhibitory role of these protein kinases in the production of neurotrophins by intact astrocytes and the absence of their participation in the regulation of functions of oligodendrocytes and microglial cells were shown. Under conditions of ethanol neurotoxicity, the role of ERK1/2 and p38 in the production of growth factors by glial elements was significantly changed. Neurodegeneration modeled in vitro led to inversion of the role of both protein kinases in the secretion of neurotrophins by astroglia and inhibition of the cytokine-synthesizing function of oligodendrocytes and microglial cells by ERK1/2 and p38. In mice receiving ethanol per os for a long time (as well as in cells in vitro exposed to ethanol), mitogen-activated kinases stimulated the function of astrocytes and inhibited the production of growth factors by microglial cells. At the same time, chronic alcoholization was accompanied by the appearance of the stimulating role of ERK1/2 and p38 in the implementation of the secretory function by oligodendrocytes.

Targeting cAMP-pathway in Regeneration-competent Cells of Nervous Tissue: Potential to Create a Novel Drug for Treatment of Ethanol-induced Neurodegeneration.

Existing neuroprotective drugs are not effective enough to treat alcoholic encephalopathy. This makes the development of novel pharmacological approaches to treating patients with ethanol-induced neurodegeneration(EIN) relevant. Therefore, the search for new targets among intracellular signaling molecules of regeneration-competent cells of nervous tissue is promising. This study aims to explore the involvement of cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) in the realization of the functions of nervous tissue progenitors and glial cells in EIN. Experiments were conducted on mice of C57B1/6. EIN was modeled in vitro and in vivo. The effects of the adenylate cyclase (AC) and PKA inhibitors on the colony-forming capacity of neural stem cells (NSC) and neuronal-committed progenitors (NCP), their proliferative activity, and intensity of specialization were investigated. The secretion of neurotrophins by astrocytes, oligodendrocytes, and microglial cells was also evaluated. Individual fractions of cells were obtained using the immunomagnetic separation method. The cAMP/PKA signaling is shown to stimulate the proliferation of the NSC and inhibit the mitotic activity of the NCP under the conditions of their optimal vital activity. cAMP reduces the specialization intensity of both types of progenitors. EIN leads to the inversion of the role of the cAMP/PKA-pathway in the regulation of NSC functions. cAMP-pathway has varying influences on the secretion of neurotrophic growth factors by glial cells depending on their living conditions. AC blockage stimulates the realization of the NSC and NCP growth potential and production of neurotrophins by astrocytes and microglial cells in EIN. These findings show the potential for the use of AC inhibitors as novel effective drugs for the therapy of alcoholic encephalopathy.

Neural stem cell therapy for brain disease

Brain diseases, including brain tumors, neurodegenerative disorders, cerebrovascular diseases, and traumatic brain injuries, are among the major disorders influencing human health, currently with no effective therapy. Due to the low regeneration capacity of neurons, insufficient secretion of neurotrophic factors, and the aggravation of ischemia and hypoxia after nerve injury, irreversible loss of functional neurons and nerve tissue damage occurs. This damage is difficult to repair and regenerate the central nervous system after injury. Neural stem cells (NSCs) are pluripotent stem cells that only exist in the central nervous system. They have good self-renewal potential and ability to differentiate into neurons, astrocytes, and oligodendrocytes and improve the cellular microenvironment. NSC transplantation approaches have been made for various neurodegenerative disorders based on their regenerative potential. This review summarizes and discusses the characteristics of NSCs, and the advantages and effects of NSCs in the treatment of brain diseases and limitations of NSC transplantation that need to be addressed for the treatment of brain diseases in the future.

Sigma–1 receptor activation alleviates blood–brain barrier disruption post cerebral ischemia stroke by stimulating the GDNF–GFRα1–RET pathway

Blood–brain barrier (BBB) disruption is one of the most important pathological manifestations of ischemic stroke. Reducing BBB collapse is effective in alleviating brain parenchymal injury and cognitive dysfunction. Our previous study reported that Sigma–1 receptor (Sig–1R) activation in cerebral microvascular endothelial cells (CMECs) ameliorated BBB impairment, but the detailed mechanism remains unclear. In this study, we investigated Sig–1R activation as a BBB integrity promoter via many post ischemic stroke pathways. Sig–1R activation in BBB–associated astrocytes can increase glia–derived neurotrophic factor (GDNF) secretion in bilateral common carotid artery occlusion (BCCAO) mice. Upregulated GDNF activates its receptors in CMECs to promote BBB integrity, and activated Sig–1R in CMECs facilitates this process. In vitro experiments have found that Sig–1R activation in CMECs promotes the interaction between the GDNF α1 receptor and transduction rearrangement gene, increasing PI3K–AKT–junction protein signaling pathway expression. Sig–1R activation could be an effective therapeutic method for preventing BBB damage in ischemic stroke and other neurological conditions.

Brain-derived neurotrophic factor in relation to central obesity in children with sleep disordered breathing.

IntroductionSleep disordered breathing (SDB) represents common comorbidities of childhood obesity leading to interrupted sleep and sleep deprivation. Sleep deprivation alters secretion of brain-derived neurotrophic factor (BDNF), which is an appetite regulator. However, little is known about the relation between BDNF and central obesity in children with SDB. The aim of the study was to evaluate BDNF level and anthropometric indices in relation to SDB in children with obesityMaterial and methodsA prospective case-control study was conducted on 30 children with obesity (BMI > 95th percentile) and 30 healthy lean children (BMI 5th-85th percentile). Polysomnographic, anthropometric data and BDNF serum level were obtained from all included children. Serum level of BDNF and anthropometric indices of obesity were assessed in relation to SDB in children with obesity. Regression analysis was done to determine predictors for SDB in children with obesity.ResultsIn comparison to healthy controls, anthropometric indices of central obesity were significantly higher while BDNF was significantly lower in obese children, especially those with SDB. Respiratory disturbance index has a significant positive correlation with anthropometric indices of central obesity and a significant negative correlation with BDNF level. Central obesity and decreased BDNF were associated with 2-fold increased risk for SDB. Waist circumference/height ratio and neck circumference/height ratio have 89.5%, 75% sensitivity and 81.23%, 84.62% specificity at a cutoff point > 0.62, > 0.24 respectively for prediction of SDB in children with obesity.ConclusionsCentral obesity and decreased BDNF represent independent predictors for SDB in children with obesity. Anthropometric indices adjusted to height are a simple screening tool for SDB in obese children.

Mesenchymal Stromal Cells Perspective: New Potential Therapeutic for the Treatment of Neurological Diseases.

Several studies have shown that mesenchymal stromal/stem cells (MSCs) exert their neuroprotective and neurorestorative efficacy via the secretion of neurotrophic factors. Based on these studies, many clinical trials using MSCs for the treatment of neurological disorders have been conducted, and results regarding their feasibility and efficacy have been reported. The present review aims to highlight the characteristics and basic research regarding the role of MSCs in neurological disease and to discuss the recent progress in clinical trials using MSCs to treat various neurological disorders.

Promising tacrine/huperzine A-based dimeric acetylcholinesterase inhibitors for neurodegenerative disorders: From relieving symptoms to modifying diseases through multitarget.

Neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease, are devastating diseases in the elderly world, which are closely associated with progressive neuronal loss induced by a variety of genetic and/or environmental factors. Unfortunately, currently available treatments for neurodegenerative disorders can only relieve the symptoms but not modify the pathological processes. Over the past decades, our group by collaborating with Profs. Yuan-Ping Pang and Paul R. Carlier has developed three series of homo/hetero dimeric acetylcholinesterase inhibitors derived from tacrine and/or huperzine A. The representative dimers bis(3)-Cognitin (B3C), bis(12)-hupyridone, and tacrine(10)-hupyridone might possess disease-modifying effects through the modulation of N-methyl-d-aspartic acid receptors, the activation of myocyte enhancer factor 2D gene transcription, and the promotion of neurotrophic factor secretion. In this review, we summarize that the representative dimers, such as B3C, provide neuroprotection against a variety of neurotoxins via multiple targets, including the inhibitions of N-methyl-d-aspartic acid receptor with pathological-activated potential, neuronal nitric oxide synthase, and β-amyloid cascades synergistically. More importantly, B3C might offer disease-modifying potentials by activating myocyte enhancer factor 2D transcription, inducing neuritogenesis, and promoting the expressions of neurotrophic factors in vitro and in vivo. Taken together, the novel dimers might offer synergistic disease-modifying effects, proving that dimerization might serve as one of the strategies to develop new generation of therapeutics for neurodegenerative disorders.

Effects of different implant surface properties on the biological behavior of Schwann cells.

This study investigated the effects of different implant surface properties on the biological behavior of Schwann cells. Schwann cells (SCs) were cultured on three types of implant surfaces including smooth polished (SMO), sand-blasted, large grit, acid-etched (SLA), and chemically-modified SLA (modSLA). At different time points, the morphology and adhesion of SCs on the implant surfaces were observed by scanning electron microscope. Cell proliferation activity was detected by MTT method. The expression levels of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) were detected by enzyme-linked immunosorbent assay. Changes in the mRNA levels of NGF and BDNF were detected by real-time fluorescent quantitative polymerase chain reaction (PCR). SCs adhered, stretched, and proliferated well on the three types of implant surfaces. On the 3rd, 5th, and 7th days, the OD values of the SMO group were higher than those of the SLA group and the modSLA group, and the difference was statistically significant (P<0.05). On the 3rd day, the expression and mRNA levels of NGF and BDNF in the SLA group and the modSLA group were higher than those in the SMO group (P<0.05); in particular, the levels in the modSLA group were higher than those in the SLA group (P<0.05). Different implant surface properties have different effects on the biological behavior of SCs. Proliferation of SCs is significantly promoted by smooth surface, while secretion and gene expression of neurotrophic factors are significantly promoted by modSLA surface at early stage.

The Interaction Between Microglia and Macroglia in Glaucoma.

Glaucoma, a neurodegenerative disease that leads to irreversible vision loss, is characterized by progressive loss of retinal ganglion cells (RGCs) and optic axons. To date, elevated intraocular pressure (IOP) has been recognized as the main phenotypic factor associated with glaucoma. However, some patients with normal IOP also have glaucomatous visual impairment and RGC loss. Unfortunately, the underlying mechanisms behind such cases remain unclear. Recent studies have suggested that retinal glia play significant roles in the initiation and progression of glaucoma. Multiple types of glial cells are activated in glaucoma. Microglia, for example, act as critical mediators that orchestrate the progression of neuroinflammation through pro-inflammatory cytokines. In contrast, macroglia (astrocytes and Müller cells) participate in retinal inflammatory responses as modulators and contribute to neuroprotection through the secretion of neurotrophic factors. Notably, research results have indicated that intricate interactions between microglia and macroglia might provide potential therapeutic targets for the prevention and treatment of glaucoma. In this review, we examine the specific roles of microglia and macroglia in open-angle glaucoma, including glaucoma in animal models, and analyze the interaction between these two cell types. In addition, we discuss potential treatment options based on the relationship between glial cells and neurons.

Orexin-A Attenuates Inflammatory Responses in Lipopolysaccharide-Induced Neural Stem Cells by Regulating NF-KB and Phosphorylation of MAPK/P38/Erk Pathways.

BackgroundNeuronal damage is the main cause of neurological diseases. Neural stem cells (NSCs) have the functions of cell repair and replacement of neurons, secretion of neurotrophic factors, and immune regulation of the neural microenvironment.ObjectivePrevious study found that Orexin-A had a protective effect on neurons in the central nervous system, but it is lacking in making great efforts on the function of Orexin-A on NSCs. This study aimed to investigate the anti-inflammatory responses and signaling mechanisms of Orexin-A on lipopolysaccharide (LPS)-induced NSCs.MethodsQuantitative real-time polymerase chain reaction was used to detect the mRNA level. Signaling pathway-related protein expression was detected by Western blot. The proliferation and migration of NSCs were investigated by Cell Counting Kit-8 (CCK-8) detection kit and transwell assay. Besides, the staining of hematoxylin and eosin (HE) was performed to study the morphology of cell.ResultsOrexin-A decreased the pro-inflammatory cytokines of IL-1β, TNF-α, and IL-6 induced by LPS by regulating nuclear factor-k-gene binding (NF-kB) and phosphorylation of P38/Erk-mitogen-activated protein kinases (MAPKs) pathways, but not p-JNK signaling.ConclusionOur findings indicate that Orexin-A can alleviate the inflammatory response of NSC. It can provide beneficial help in neural stem cell therapy applications.

Potential of N-trans feruloyl tyramine from Lycium barbarum fruit extract on neurogenesis and neurotrophins; targeting TrkA/ERK/CREB signaling pathway

This study was aimed to evaluate the potential neurotrophic effect of Lycium barbarum fruit extract (LB-E) via increased neurite outgrowth and synaptic formation, and its neurotrophic and neuroprotective efficacy was also checked in vitro. LB-E exerted neurotrophic effects by regulating TrkA/ERK/CREB signaling. In nervous system, LB-E promoted neuronal survival and differentiation by increasing neurotrophic factor secretion in C6 glioma cells. Interestingly, LB-E increased the expressed levels of synaptophysin and GAP-43 in CNS cell lines. It also subsequently increased the number of ciliated cells and length of cilia in N1 hypothalamic neuronal cells induced by CNTF and displayed the enhanced dendrite length in primary cortical neurons. We investigated N-trans feruloyl tyramine (NTFT) from LB-E by LC-MS/MS, and confirmed NTFT as a biologically active ingredient showing the neurotrophic effect. These results suggested that NTFT from LB-E may be beneficial in the treatment of age-related brain diseases caused by the deficiency of neurotrophins.

Mechanisms linking gut microbiota to depression

IntroductionThe gut microbiota constitute the largest and most diverse community in the body which is primarily responsible for the maintenance of the intestinal wall integrity and the protection against pathogens. Besides having an important role in the regulation of host energy metabolism, the gut microbiota can also influence neurodevelopment, modulate behavioral and might contribute to the development of psychiatry disorders.ObjectivesThe authors elaborated a narrative literature review to understand how gut microbiota can influence depression.MethodsUsing PubMed as the database, a research was conducted about how Gut Microbiota relates with Depression.ResultsThe microbiota-gut-brain axis encompasses the strong bidirectional communication between the gut microbiota and the CNS. Multiple mechanisms may be involved in this bilateral communication, including immune, endocrine and neural pathways. Permutations in the gut microbiome composition trigger microbial lipopolysaccharides production that activates inflammatory responses. Cytokines send signals to the vagus nerve, which links the process to the hypothalamic-pituitary-adrenal axis that consequently causes behavioral effects. Beyond this, gut microbiota have the capacity to produce many neurotransmitters and neuromodulators such as serotonin and can induce the secretion of the brain-derived neurotrophic factor, an important plasticity-related protein that promotes neuronal growth, development and survival.ConclusionsNeuroinflammatory processes like those that occur in depression are deeply modulated by peripheral inflammatory stimuli, especially those from the intestinal microbiota. However, the knowledge is currently limited and the information available is not enough to understand the exact mechanisms. Therefore, more studies are required to show how gut microbiota influences the human brain.DisclosureNo significant relationships.

Evaluation of plasma levels of BDNF in patients with disorder depressive

IntroductionAccording to the World Health Organization (WHO, 2017) depressive disorder continues to be the most widespread and growing mental illness in the world, also assumes that in 2020 depression will have a prevalence equal to one in six individuals. Studies of neuroanatomy have highlighted structural alterations in the hippocampus, striatal nuclei and prefrontal cortex in patients with mood disorders. This alteration in depressed patients is closely related to the secretion of neurotrophic factors, in particular there is a reduction in BDNF (Brain Derived Neurotrophic Factor).ObjectivesThe objective of this study is to demonstrate which treatments are effective in reducing depressive symptoms that allow the increase of BDNF and consequently the structural homostaticity of the brain.MethodsWe have selected data from the literature of the last decade, collected on major search engines such as: Google Scholar, Research Gate, PubMed, Ebsco. Articles collected by selecting the following Keyword: depression, BDNF (Brain Derived Neurotrophic Factor), neuroimaging cognitive behavior therapy.ResultsThe results show that in patients treated with a single drug treatment or vagus nerve stimulation, repetitive transcranial magnetic stimulation (Lang et al., 2008) or electroconvulsive therapy had improvements in BDNF levels, although compared to drug treatment there are problems of no responders, no compliance and lack of effectiveness in reducing vulnerability to relapse. In addition, the study has shown that patients treated with cognitive behavioral therapy have reported greater changes in the frontal and temporal cortex reducing both depressive symptoms and the risk of relapse.ConclusionsUnderlines the importance of an integrated approach

Prospects of Therapeutic Target and Directions for Ischemic Stroke.

Stroke is a serious, adverse neurological event and the third leading cause of death and disability worldwide. Most strokes are caused by a block in cerebral blood flow, resulting in neurological deficits through the death of brain tissue. Recombinant tissue plasminogen activator (rt-PA) is currently the only immediate treatment medication for stroke. The goal of rt-PA administration is to reduce the thrombus and/or embolism via thrombolysis; however, the administration of rt-PA must occur within a very short therapeutic timeframe (3 h to 6 h) after symptom onset. Components of the pathological mechanisms involved in ischemic stroke can be used as potential biomarkers in current treatment. However, none are currently under investigation in clinical trials; thus, further studies investigating biomarkers are needed. After ischemic stroke, microglial cells can be activated and release inflammatory cytokines. These cytokines lead to severe neurotoxicity via the overactivation of microglia in prolonged and lasting insults such as stroke. Thus, the balanced regulation of microglial activation may be necessary for therapy. Stem cell therapy is a promising clinical treatment strategy for ischemic stroke. Stem cells can increase the functional recovery of damaged tissue after post-ischemic stroke through various mechanisms including the secretion of neurotrophic factors, immunomodulation, the stimulation of endogenous neurogenesis, and neovascularization. To investigate the use of stem cell therapy for neurological diseases in preclinical studies, however, it is important to develop imaging technologies that are able to evaluate disease progression and to “chase” (i.e., track or monitor) transplanted stem cells in recipients. Imaging technology development is rapidly advancing, and more sensitive techniques, such as the invasive and non-invasive multimodal techniques, are under development. Here, we summarize the potential risk factors and biomarker treatment strategies, stem cell-based therapy and emerging multimodal imaging techniques in the context of stroke. This current review provides a conceptual framework for considering the therapeutic targets and directions for the treatment of brain dysfunctions, with a particular focus on ischemic stroke.

Synergistic neuroprotective effects of Fingolimod and mesenchymal stem cells (MSC) in experimental autoimmune encephalomyelitis

Fingolimod (Gilenya™) is an effective oral medication approved for relapsing-remitting multiple sclerosis (MS), albeit less effective in chronic disease. Its main mechanism of action is through peripheral immunomodulation but neuroprotective effects may also be involved. Mesenchymal stem cells (MSC) were shown to exert immunomodulatory and neurotrophic effects in the model of multiple sclerosis (experimental autoimmune encephalomyelitis-EAE). The use of combination treatments in chronic diseases such as MS, has long been advocated and may result in improvement of the beneficial effects of each one of them.We tested the in vitro effects of Fingolimod (FTY720) on MSC and the in vivo effect of such combination treatment in the model of EAE.Fingolimod did not affect in any detrimental way the basic features of MSCs and it promoted their migration and proliferation ability .Moreover, Fingolimod induced neurotrophic factors secretion and suppressed the production of pro-inflammatory cytokines from astrocytes and microglia, in vitro. In vivo, the combined treatment of FTY720 and MSC (either by the intravenous or the intra-cerebroventricular route of administration) resulted in synergistic clinical beneficial effects compared to FTY720 or MSC alone, paralleled by a significant reduction of inflammatory CNS infiltrations and of axonal loss. These data may indicate a synergism of fingolimod with MSC and may support future combinations of immunomodulatory drugs with cellular therapies for the improvement of the benefits in progressive forms of MS.

EphA4 Obstructs Spinal Cord Neuron Regeneration by Promoting Excessive Activation of Astrocytes

Studies have found that molecular targets that regulate tissue development are also involved in regulating tissue regeneration. Erythropoietin-producing hepatocyte A4 (EphA4) not only plays a guiding role in neurite outgrowth during the development of the central nervous system (CNS) but also induces injured axon retraction and inhibits axon regeneration after spinal cord injury (SCI). EphA4 targets several ephrin ligands (including ephrin-A and ephrin-B) and is involved in cortical cell migration, axon guidance, synapse formation and astrocyte function. However, how EphA4 affects axon regeneration after SCI remains unclear. This study focuses on the effect and mechanism of EphA4-regulated astrocyte function in neuronal regeneration after SCI. Our research found that EphA4 expression increased significantly after SCI and peaked at 3 days post-injury; accordingly, we identified the cellular localization of EphA4 and ephrin-B ligands in neurons and astrocytes after SCI. EphA4 was mainly expressed on the surface of neurons, ephrin-B1 and ephrin-B3 were mainly localized on astrocytes, and ephrin-B2 was distributed on both neurons and astrocytes. To further elucidate the effect of EphA4 on astrocyte function after SCI, we detected the related cytokines secreted by astrocytes in vivo. We found that the levels of neurotrophic factors including nerve growth factor (NGF) and basic fibroblast growth factor (bFGF) increased significantly after SCI (NGF peaked at 3 days and bFGF peaked at 7 days); the expression of laminin and fibronectin increased gradually after SCI; the expression of inflammatory factors [interleukin (IL)-1β and IL-6] increased significantly from 4 h to 7 days after SCI; and the levels of glial fibrillary acidic protein (GFAP), a marker of astrocyte activation, and chondroitin sulphate proteoglycan (CSPG), the main component of glial scars, both peaked at 7 days after SCI. Using a damaged astrocyte model in vitro, we similarly found that the levels of related cytokines increased after injury. Consequently, we observed the effect of damaged astrocytes on neurite outgrowth and regeneration, and the results showed that damaged astrocytes hindered neurite outgrowth and regeneration; however, the inhibitory effect of injured astrocytes on neurite regeneration was reduced following ephrin-B receptor knockdown or inflammatory inhibition at 24 h after astrocyte injury. Our results showed that EphA4 regulates the secretion of neurotrophic factors, adhesion molecules, inflammatory factors and glial scar formation by binding with the ligand ephrin-B located on the surface of astrocytes. EphA4 affects neurite outgrowth and regeneration after SCI by regulating astrocyte function.

Sea urchin gangliosides exhibit neuritogenic effects in neuronal PC12 cells via TrkA- and TrkB-related pathways.

Gangliosides (GLSs) are ubiquitously distributed in all tissues but highly enriched in nervous system. Currently, it is unclear how exogenous GLSs regulate neuritogenesis, although neural functions of endogenous GLSs are widely studied. Herein, we evaluated the neuritogenic activities and mechanism of sea urchin gangliosides (SU-GLSs) in vitro. These different glycosylated SU-GLSs, including GM4(1S), GD4(1S), GD4(2A), and GD4(2G), promoted differentiation of NGF-induced PC12 cells in a dose-dependent and structure-selective manner. Sulfate-type and disialo-type GLSs exhibited stronger neuritogenic effects than monosialoganglioside GM1. Furthermore, SU-GLSs might act as neurotrophic factors possessing neuritogenic effects, via targeting tyrosine-kinase receptors (TrkA and TrkB) and activating MEK1/2-ERK1/2-CREB and PI3K-Akt-CREB pathways. This activation resulted in increased expression and secretion of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). These pathways were verified by specific inhibitors. Our results confirmed the neuritogenic functions of SU-GLS in vitro and indicated their potential roles as natural nutrition for neuritogenesis.

Czy intensywny wysiłek fizyczny może być lekiem w chorobie Parkinsona?

Badania naukowe wskazują, że aktywność fizyczna wpływa nie tylko na polepszenie ogólnego stanu zdrowia u ludzi, ale dowodzą również specyficznego wpływu ćwiczeń fizycznych na "zdrowie mózgu". Doniesienia ostatnich lat pokazują, że uprawianie aktywności fizycznej w młodym wieku obniża ryzyko zachorowania na choroby neurodegeneracyjne, np. na chorobę Parkinsona. Jednocześnie istnieje wiele badań naukowych, prowadzonych na zwierzętach i ludziach wskazujących, że ćwiczenia fizyczne wywołują korzystne zmiany neuroplastyczne w mózgu zarówno u ludzi zdrowych jak i u chorujących na choroby neurodegeneracyjne. Niniejszy artykuł przedstawia dowody naukowe na zmiany neuroprotekcyjne i neuronaprawcze w mózgu wywołane ćwiczeniami fizycznymi. Zagadnieniem które szerzej podjęto w niniejszym artykule jest wpływ ćwiczeń fizycznych o wysokiej intensywności na zmiany neuroplastyczne i mechanizmy neurofizjologiczne ośrodkowego układu nerwowego oraz na zachowania psychomotoryczne w chorobie Parkinsona. Przedstawione w niniejszym artykule dowody naukowe na pozytywne efekty wysiłku fizycznego na ośrodkowy układ nerwowy to: (i) wzrost wydzielania czynników neurotroficznych, (ii) wzrost ekspresji receptorów dopaminergicznych D2 w prążkowiu, (iii) spadek aktywności transportera dopaminergicznego, (iv) wydłużenie korowo-rdzeniowego okresu ciszy u pacjentów z chorobą Parkinsona zbadanego za pomocą metody przezczaszkowej stymulacji magnetycznej, (v) poprawa sprawności czynności ruchowych oburęcznych, (vi) poprawa funkcji kognitywnych oraz (viii) złagodzenie symptomów ruchowych i pozaruchowych choroby Parkinsona. Wiedza ta jest ważna dla fizjoterapeutów poszukujących skutecznych metod terapii ruchem opartych na dowodach naukowych, wskazujących na wpływ odpowiednio dozowanego wysiłku na patomechanizm choroby Parkinsona, jak również dla modyfikacji systemu opieki zdrowotnej. Niniejszy artykuł ma również uświadomić każdemu z nas, jak wielki wpływ mamy na nasze "zdrowie mózgu" gdy regularnie uprawiamy aktywność fizyczną na każdym etapie naszego życia.

Mesenchymal Stem Cells Derived from Wharton's Jelly Can Differentiate into Schwann Cell-Like Cells and Promote Peripheral Nerve Regeneration in Acellular Nerve Grafts.

Schwann cells (SCs) secrete neurotrophic factors and provide structural support and guidance during axonal regeneration. However, nearby nerves may be damaged to obtain primary SCs, and there is a lack of nervous tissue donors. We investigated the potential of Wharton's Jelly-derived mesenchymal stem cells (WJ-MSCs) in differentiating into Schwann cell-like cells (WJ-SCLCs) as an alternative to SCs. We also examined whether implantation of WJ-SCLCs-laden acellular nerve grafts (ANGs) are effective in inducing functional recovery and nerve regeneration in an animal model of peripheral nerve injury. The differentiation of WJ-MSCs into WJ-SCLCs was determined by analyzing SC-specific markers. The secretion of neurotrophic factors was assessed by the Neuro Discovery antibody array. Neurite outgrowth and myelination of axons were found in a co-culture system involving motor neuron cell lines. The effects of ANGs on repairing sciatic nerves were evaluated using video gait angle test, isometric tetanic force analysis, and toluidine blue staining. Compared with undifferentiated WJ-MSCs, WJ-SCLCs showed higher expression levels of SC-specific markers such as S100β, GFAP, KROX20, and NGFR. WJ-SCLCs also showed higher secreted amounts of brain-derived neurotrophic factor, glial cell-derived neurotrophic factor, and granulocyte-colony stimulating factor than did WJ-MSCs. WJ-SCLCs effectively promoted the outgrowth and myelination of neurites in motor neuron cells, and WJ-SCLCs laden ANGs significantly facilitated peripheral nerve regeneration in an animal model of sciatic nerve injury. WJ-MSCs were readily differentiated into WJ-SCLCs, which effectively promoted the regeneration of peripheral nerves. Transplantation of WJ-SCLCs with ANGs might be useful for assisting peripheral nerve regeneration.

Biomimetic electrospun tubular PLLA/gelatin nanofiber scaffold promoting regeneration of sciatic nerve transection in SD rat

The micro- or nanoscale surface morphology of the tissue engineering nerve guidance scaffold (NGS) will affect different cell behaviors, such as their growth rate, migration, and matrix secretion. Although different technologies for manufacturing scaffolds with biomimetic topography have been established, most of them tend to be high cost and long preparation time. Here we have prepared a biomimetic NGS with physical properties to simulate native nerve tissue more accurately. We used poly(l-lactic acid) (PLLA) nanofibers doped with gelatin to prepare a biomimetic NGS whose structure mimics the native epineurium layer. By adjusting the doping ratio of gelatin and PLLA in the tubular scaffold, the bionic scaffold's surface morphology and mechanical properties are closer to native tissues. In vitro cell scaffold interaction experiments demonstrated that the PLLA/gelatin nanofibers could significantly promote the elongation, proliferation, and the secretion of glial cell-derived neurotrophic factor (GDNF) of RSC96 Schwann cells (SCs), as well as the diffusion of GDNF. In vivo scaffold replacement of SD rat, sciatic nerves showed that the nerve guide scaffold composed of PLLA/gelatin nanofibers was helpful to the myelination of SCs and the remolding of epineurium in the injured area, which could effectively rehabilitate the motor and sensory functions of the injured nerve and prevent the atrophy of the target muscle tissue. This study showed that the synergistic impact of nano topographical and biochemical clues on designing biomimetic scaffolds could efficiently promote regenerating nerve tissue.