Role Of Neurotrophic Factor Research Articles

Yoga Induced Brain Plasticity- Role of Neurotrophic Factors

Yoga Induced Brain Plasticity- Role of Neurotrophic Factors

Role of Neurotrophic Factors in Parkinson's Disease.

Parkinson's disease is an age-associated progressive neurodegenerative disorder that has gained crescent social and economic impact due to the aging of the western society. All current therapies are symptomatic and fail to reverse or halt the progression of dopaminergic neurons loss. The discovery of the capability of neurotrophic factors to protect these neurons lead numerous research groups to focus their efforts in developing therapies aiming at promoting the control of Parkinson´s disease through the delivery of neurotrophic factors to the brain or by boosting their endogenous levels. Both strategies were successful in inducing protection of dopaminergic neurons and motor recovery in preclinical models of the disease. Contrariwise, very limited success was obtained in clinical studies, where glial cell line-derived neurotrophic factor and neurturin were the neurotrophic factors of choice for Parkinson's disease therapy. These drawbacks motivate the development of novel forms of delivery or the modification of the injected molecules aiming at providing a more stable and effective administration with improved diffusion in the target tissue, and without the immune responses observed in the earliest clinical studies. Although promising results were obtained with some of these new approaches performed in experimental models of the disease, they were not yet tested in human studies. In this review, we present the current knowledge on neurotrophic factors and their role in Parkinson's disease, focusing on the strategies that have been developed to increase their levels in target areas of the brain to achieve protection of dopaminergic neurons and motor behaviour recovery.

HIV, Alcohol Use Disorders and Pain: New Findings to Address the Problem

Background: Alcohol use and pain are frequent problems among people living with HIV/AIDS (PLWHA). Therefore, increasing the understanding of the interaction between these medical conditions is critical to improve health care and quality of life forthis population. While gender differencesin alcohol use andmood disorders are widely recognized, little is known about gender disparities in prescription of painkillers and correlates. Equally important is the lack of information regarding the role of neurotrophic factors although animal models have demonstrated BDNF pronociceptive effects. Methods: Using a clinic-based sample of people living with H.I.V/AIDS (PLWHA), we investigated the prevalence and correlates associations of recent pain killer use. We also assessed the effects of gender, mood and Brain Derived Neurotrophic Factor levels (BDNF). Participants were 400 people living with HIV (PLWHA) who participated in the PADS cohort study. Results: Approximately, a quarter (24%) of the sample reported regularly taking painkillers, and a correlation was evident with both CD4s and viral loads. Painkiller users were typically over 40. Ifthey weremales, painkiller users weremore likely to be Caucasian; however, painkiller female users were more likely to be minorities. Factors related to painkiller use also differed between men and women. Analyses demonstrated that the weekly consumption of alcohol was significantly higher in the painkiller group compared to controls (19.4 ± 3.9 vs. 15.9 ± 1.34 drinks/week; p=0.03). Compared to non-hazardous alcohol users (non-HAU), female-hazardous alcohol users (HAU’s) were more likely to be using prescription opioids (Odds Ratio: 4.6 95% Confidence Interval: 1-22.9, p=0.04). No such trend was observed among males. Noteworthy, higher scores of both depression and stress were observed among painkiller users. Gender differences were notable; women using painkillers exhibited significantly higher scores on both depression (19.6 ± 12.4 vs. 13.6 ± 11.7 total score; p=0.01), and stress (19.4 ± 8.3 vs. 14.9 ± 8.1 total score; p=0.004) while men did not. In our analyses, BDNF levels were significantly higher among subjects taking painkillers than those not taking them. In Longitudinal analyses, confirmed that hazardous alcohol use, BDNF levels, and gender were associated with greater odds of using painkillers at 6 months. Conclusion: These findings highlight the importance of designing gender-sensitive surveillance, prevention, and treatment. Our findings extend earlier research by revealing that BDNF may account for important aspects of pain and alcohol abuse. The apparent implication of these findings is that interventions targeting BDNF may have considerable therapeutic potential in this population

Role of neurotrophic factors and chemokines in perineural invasion in pancreatic cancer

Role of neurotrophic factors and chemokines in perineural invasion in pancreatic cancer

Neurotrophic factors: promising candidates in tissue regeneration.

Neurotrophic factors: promising candidates in tissue regeneration.

Is there a role for neurotrophic factors and their receptors in augmenting the neuroprotective effect of (−)-epigallocatechin-3-gallate treatment of sciatic nerve crush injury?

This study analyzed and compared the effects of EGCG treatment on the expression of NTFs and NTF receptors expression in the sciatic nerve and the L3–L6 spinal cord segments at the early phase of regeneration following sciatic nerve crush injury. Analysis of BDNF, GDNF and NT3 neurotropic factors and Trk-B, Trk-C and NGFR-p75 receptors in neurons in the spinal cord of CRUSH and CRUSH + EGGC rats showed significant (p < 0.0001) decrease compared to NAÏVE and SHAM at day 1, 3, 7 and 14 after nerve injury. EGCG treatment significantly (p < 0.0001) increased the BDNF, GDN, NT3, Trk-B, Trk-C and NGFR-p75 immunostaining in the L3–L6 spinal cord compared to CRUSH animals. Also, EGCG treatment significantly increased the Trk-B protein concentration and Trk-B, NT3 and Trk-C gene expression in the spinal cords compared to CRUSH group. However, at day 1 and 3 post nerve injury, EGCG treatment significantly decreased the NGFR-p75 expression compared to CRUSH rats. In the sciatic nerve, EGCG treatment significantly (p < 0.01) increased the Trk-B and NGFR-p75 protein concentration in the controls. EGCG treatment significantly (p < 0.0001) increased the Trk-B, Trk-C and NGFR-p75 mRNA gene expressions in the sciatic nerves compared to CRUSH group. Only at day 1, CRUSH + EGCG animals displayed significant rise in the sciatic nerves NT3 gene expression compared to CRUSH group. Our data suggest that the EGCG neuroprotective effect on the spinal cord neurons may be mediated through the modulation of NTFs and NTF receptors following nerve crush injury in a rat model.

Effect of selegiline on neural stem cells differentiation: a possible role for neurotrophic factors.

The stimulation of neural stem cells (NSCs) differentiation into neurons has attracted great attention in management of neurodegenerative disease and traumatic brain injury. It has been reported that selegiline could enhance the morphologic differentiation of embryonic stem cells. Therefore this study aimed to investigate the effects of selegiline on NSCs differentiation with focus on the role of neurotrophic factor gene expression. The NSCs were isolated from lateral ventricle of C57 mice brain. The cells were exposed to selegiline in nano to micromolar concentrations for 24 hr or 72 hr. In order to assay the effect of selegiline on NSCs differentiation into neurons, astrocytes and oligodendrocytes, immunocytochemical techniques were utilized. Samples were exposed to specific antibodies against neurons (β tubulin), astrocytes (GFAP) and oligodendrocytes (OSP). The expression of BDNF, NGF and NT3 genes was investigated using Real-Time PCR. Our findings revealed that selegiline increased NSCs differentiation into neurons at 10(-7) and 10(-8) M and decreased the differentiation into astrocytes at 10(-9), while oligodendrocyte did not significantly change in any of the used concentrations. In addition data analyses showed that selegiline increased BDNF, NGF and NT3 gene expression at 24 hr, but did not change them in the other time of exposure (72 hr) except 10(-7) M concentration of selegiline, which increased NT3 expression. Our results indicate selegiline induced the differentiation of NSCs into neurons and in this context the role of neurotrophic factors is important and should be considered.

Migraine is associated with altered levels of neurotrophins

Neurotrophic factors have been implicated in hyperalgesia and peripheral levels of these molecules were altered in behavioral and neurological disorders. The objectives of this study were to assess neurotrophic factors levels in migraine patients in comparison with controls, and to investigate whether there was any association between them and clinical parameters. This was a cross-sectional study. We measured serum levels of neurotrophin family members – nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 and 4/5 (NT3 and NT4/5) – and glial cell line-derived factor (GDNF) in patients suffering from migraine and matched controls. One hundred forty-one people were enrolled in this study, seventy-one were migraine patients and seventy were controls. Migraine patients showed more depressive and anxiety symptoms than control individuals as assessed, respectively, by the Beck Depression Inventory (BDI) and the Beck Anxiety Inventory. Chronic and episodic migraine patients showed higher NT4/5 levels than control individuals (P=0.001). Patients with chronic migraine had lower levels of BDNF that were not influenced by the presence of depressive symptoms (P=0.02). This is the first report to evaluate NT3 and NT-4/5 levels in migraine patients. Our findings suggest a possible role of neurotrophic factors in migraine pathophysiology.

Decreased serum level of NGF in alcohol-dependent patients with declined executive function.

The role of neurotrophic factors has been highlighted as a cause of decline in the cognitive function of alcohol-dependent patients. It is known that nerve-growth factor (NGF), one of the neurotrophins, is related to the growth and differentiation of nerve cells, as well as to a decline in cognitive function. The purpose of this study was to investigate the relationship between decreased NGF levels and cognitive decline in alcohol-dependent patients. The serum concentration of NGF was measured in 38 patients with chronic alcohol dependence, and several neuropsychological tests were also performed for cognitive function assessment. The results indicated a significant correlation between serum NGF level and the trail-making test part B, which evaluates executive function, but did not show a significant correlation with other cognitive function tests. An increased serum level of NGF was associated with a decreased completion time in the trail-making test B, and this finding indicates that a high serum level of NGF is related to greater executive function. This finding may imply a protective role of NGF in preventing neuron damage among patients with alcohol dependence. Larger controlled studies will be necessary in the future to investigate this issue further.

Mo2036 Remodeling of Colonic Sensory Afferents in a Rat Model of Post-Infectious Gut Dysfunction: Implication of Neurotrophic Factors

Background: Inflammation-induced visceral hypersensitivity is associated, at least partially, to peripheral sensitization of sensory afferents by locally released neurotrophic factors. Aims: Here, we explore the potential role of neurotrophic factors in long-term changes in visceral afferents innervating non-primary areas of inflammation (colon) in a rat model of Trichinella spiralis (TS)-induced gut dysfunction. Methods: Inflammatory-like changes, mucosal mast cells (MMCs) dynamics, and expression of nerve growth factor (NGF) and glial cell linederived neurotrophic factors (GDNF, artemin and neurturin) were determined in the colon of control and TS-infected rats, up to day 30 post-infection (PI). Markers of sensory afferents (high affinity nerve growth factor receptor, TrkA; GDNF family receptor alpha 3, GFRα3; calcitonin gene-related peptide, CGRP; and transient receptor potential vanilloid channel1, TRPV1) were assessed in thoracolumbar (T12-L2, TL) and lumbosacral (L6-S2, LS) DRGs. Functionality of colonic afferents at 14 and 30 days PI was determined by assessing changes in TRPV1 levels in TL and LS DRGs following intracolonic capsaicin. Results: TS infection induced a primary jejunitis with concomitant inflammatory-like changes in the colon: an increase in histological scores, IL-13 up-regulation and MMC infiltration (Table 1). Inflammation was partly resolved at day 30 PI, except for a persistent MMC infiltrate (Table 1). Colonic expression of neurotrophic factors showed a transient reduction by day 14 PI (25%50%), with the exception of artemin that showed a biphasic response with an up-regulation (by 30%; P<0.05) at day 30 PI (Table 2). Overall, TS infection did not affect DRG expression of none of the genes assessed, except for a transient down-regulation of TPRV1 in TL DRGs at day 14 PI. Afferent stimulation with intracolonic capsaicin induced a down-regulation of TRPV1 expression in TL and LS DRGs, an effect significantly enhanced in LS DRGs of TSinfected rats, at either 14 or 30 days PI (Table 2). Intracolonic capsaicin also up-regulated peripheral artemin in non-infected rats, an effect absent in TS-infected animals at day 30 PI (Table 2). Capsaicin-induced changes in colonic expression of artemin correlated negatively with the down-regulation of TRPV1 in LS DRGs. Conclusions: During intestinal inflammation, changes in expression of neurotrophic factors and remodeling of visceral afferents are observed outside the primary region affected by the inflammatory insult. These observations suggest that extended remodelation of sensory afferents, probably related to local changes in neurotropins, might occur during inflammatory conditions of the gut. Similar mechanisms might be operating in states of widespread alterations of visceral sensitivity. Table 1 Colonic inflammation-related changes during T. spiralis infection

(362) The effects of voluntary wheel running on pain

Chronic pain is a major public health problem, afflicting more of the general population than cardiovascular disease, diabetes, and cancer combined. Despite the prevalence of chronic pain, clinically prescribed analgesics with high efficacy often have undesirable off-target effects. Exercise is commonly prescribed to chronic pain patients and gives rise to analgesia in some cases. Preclinical animal models support a conserved mechanism for exercise-induced analgesia as exercise attenuates hypersensitivity in rodent inflammatory and neuropathic pain models. The cellular mechanisms that mediate the therapeutic effects of exercise are not well characterized, though a role for neurotrophic factors has been suggested. Exercise significantly increases neurotrophic factor levels in the central nervous system, and in turn, is associated with enhanced functional plasticity. We hypothesize that analogous changes in the peripheral nervous system underlie exercise-induced analgesia. Understanding these mechanisms may aid development of novel analgesics. To investigate the behavioral effects of exercise in mice, we are testing the effects of voluntary wheel running on thermal and mechanical sensitivity and in acute pain models, as compared to sedentary control animals. To elucidate the cellular mechanisms underlying the effects of exercise, neurotrophic factor levels in dorsal root ganglia and spinal cord are being quantified biochemically as candidate signaling molecules involved in exercise-induced analgesia. These studies will enhance our understanding of both the molecular effects exercise, and more broadly, our comprehension of pain modulation. Supported by NINDS grant R01NS042595. Chronic pain is a major public health problem, afflicting more of the general population than cardiovascular disease, diabetes, and cancer combined. Despite the prevalence of chronic pain, clinically prescribed analgesics with high efficacy often have undesirable off-target effects. Exercise is commonly prescribed to chronic pain patients and gives rise to analgesia in some cases. Preclinical animal models support a conserved mechanism for exercise-induced analgesia as exercise attenuates hypersensitivity in rodent inflammatory and neuropathic pain models. The cellular mechanisms that mediate the therapeutic effects of exercise are not well characterized, though a role for neurotrophic factors has been suggested. Exercise significantly increases neurotrophic factor levels in the central nervous system, and in turn, is associated with enhanced functional plasticity. We hypothesize that analogous changes in the peripheral nervous system underlie exercise-induced analgesia. Understanding these mechanisms may aid development of novel analgesics. To investigate the behavioral effects of exercise in mice, we are testing the effects of voluntary wheel running on thermal and mechanical sensitivity and in acute pain models, as compared to sedentary control animals. To elucidate the cellular mechanisms underlying the effects of exercise, neurotrophic factor levels in dorsal root ganglia and spinal cord are being quantified biochemically as candidate signaling molecules involved in exercise-induced analgesia. These studies will enhance our understanding of both the molecular effects exercise, and more broadly, our comprehension of pain modulation. Supported by NINDS grant R01NS042595.

AB0015 Association between bdnf, ntrk2 and creb1 gene polymorphisms and fibromyalgia

BackgroundStudies over the past 20 years have shown that fibromyalgia (FM) is a pain amplification disorder with clear evidence for a pathogenesis within the central nervous system. Brain-derived neurotrophic factor...

Brain-derived neurotrophic factor and the course of experimental cerebral malaria

The role of neurotrophic factors on the integrity of the central nervous system (CNS) during cerebral malaria (CM) infection remains obscure, but the long-standing neurocognitive sequelae often observed in rescued children can be attributed in part to the modulation of neuronal survival and synaptic plasticity. To discriminate the contribution of key responses in the time-sequence of the pathogenic events that trigger the development of neurocognitive malaria syndrome we defined four stages (I–IV) of the neurological progression of CM in C57BL/6 mice infected with Plasmodium berghei ANKA. Upregulation of ICAM-1, VCAM-1, e-selectin and p-selectin expression was detected in all cerebral regions before parasitized red blood cells (pRBC) accumulation. As the severity of symptoms increased, BDNF mRNA progressively diminished in several brain regions, earliest in the thalamus–hypothalamus, cerebellum, brainstem and cortex, and correlated with a four-stage disease sequence. Immunohistochemical confocal microscopy revealed changes in the BDNF distribution pattern, suggesting altered axonal transport. During CM progression, molecular markers of neurological infection and inflammation in the parasite and the host, respectively, were accompanied by a switch in the brain constitutive proteasome to the immunoproteasome, which could impede normal protein turnover. In parallel with BDNF downregulation, NCAM expression also diminished with increased CM severity. Together, these data suggest that changes in BDNF availability could be involved in the pathogenesis of CM.

Ageing of enteric neurons: oxidative stress, neurotrophic factors and antioxidant enzymes

BackgroundAgeing is associated with gastrointestinal dysfunction, which can have a major impact on quality of life of the elderly. A number of changes in the innervation of the gut during ageing have been reported, including neuronal loss and degenerative changes. Evidence indicates that reactive oxygen species (ROS) are elevated in ageing enteric neurons, but that neurotrophic factors may reduce generation of neuronal ROS. Two such factors, glial cell line derived neurotrophic factor (GDNF) and neurotrophin-3 (NT-3) have also been found to protect enteric neurons against oxidative stress induced cell death of enteric ganglion cells in vitro. We have investigated the possible roles of neurotrophic factors further, by examining their expression in the gut during ageing, and by analysing their effects on antioxidant enzyme production in cultures of enteric ganglion cells.ResultsAnalysis of the expression of GDNF and its receptors c-Ret and GFR α − 1 in rat gut by RT-PCR showed that expression continues throughout life and into ageing, in both ad libitum(AL) and calorically-restricted (CR) animals. Levels of expression of GDNF and GFR α − 1 were elevated in 24 month AL animals compared to 24 month CR animals, and to 24 CR and 6 month control animals respectively. The related factor Neurturin and its receptor GFR α − 2 were also expressed throughout life, the levels of the GFR – α-2(b) isoform were reduced in 24 m AL animals. Immunolabelling showed that c-Ret and GFR α − 1 proteins were expressed by myenteric neurons in ageing animals. GDNF, but not NT-3, was found to increase expression of Cu/Zn superoxide dismutase and catalase by cultured enteric ganglion cells.ConclusionsThe neurotrophic factors GDNF and neurturin and their receptors continue to be expressed in the ageing gut. Changes in the levels of expression of GDNF , GFR α-1 and GFR α-2(b) isoform occurred in 24 m AL animals. GDNF, but not NT-3, increased the levels of antioxidant enzymes in cultured enteric ganglion cells, indicating a possible mechanism for the reported protective effect of GDNF against menadione-induced neuronal apoptosis in the ageing gut. Together these data suggest that GDNF family members may play a protective role in the gut throughout life, and support the suggestion that dysregulation of neurotrophic factor support could contribute to neuronal ageing in the gut.

Neuropeptide regulation of fear and anxiety: Implications of cholecystokinin, endogenous opioids, and neuropeptide Y

The neural circuitry of fear likely underlies anxiety and fear-related disorders such as specific and social phobia, panic disorder, and posttraumatic stress disorder. The primary pharmacological treatments currently utilized for these disorders include benzodiazepines, which act on the GABAergic receptor system, and antidepressants, which modulate the monamine systems. However, recent work on the regulation of fear neural circuitry suggests that specific neuropeptide modulation of this system is of critical importance. Recent reviews have examined the roles of the hypothalamic-pituitary-adrenal axis neuropeptides as well as the roles of neurotrophic factors in regulating fear. The present review, instead, will focus on three neuropeptide systems which have received less attention in recent years but which are clearly involved in regulating fear and its extinction. The endogenous opioid system, particularly activating the μ opioid receptors, has been demonstrated to regulate fear expression and extinction, possibly through functioning as an error signal within the ventrolateral periaqueductal gray to mark unreinforced conditioned stimuli. The cholecystokinin (CCK) system initially led to much excitement through its potential role in panic disorder. More recent work in the CCK neuropeptide pathway suggests that it may act in concordance with the endogenous cannabinoid system in the modulation of fear inhibition and extinction. Finally, older as well as very recent data suggests that neuropeptide Y (NPY) may play a very interesting role in counteracting stress effects, enhancing extinction, and enhancing resilience in fear and stress preclinical models. Future work in understanding the mechanisms of neuropeptide functioning, particularly within well-known behavioral circuits, are likely to provide fascinating new clues into the understanding of fear behavior as well as suggesting novel therapeutics for treating disorders of anxiety and fear dysregulation.

Exogenous EGF and BDNF treatment enhances differentiation and proliferation of cultured taste cells

To determine the effects of epidermal growth factor (EGF) and brain-derived neurotrophic factor (BDNF) on taste cell generation by utilizing a long-term rat taste cell culture that exhibits molecular and functional characteristics of mature taste cells. The role of neurotrophic factors in taste cell development is not well understood. Materials and methods: A long-term rat taste cell culture exhibiting molecular and functional characteristics of mature taste cells was used. The effects of 3 different concentrations of EGF and BDNF on taste cell differentiation and proliferation were examined at 3 different time points. Results: We showed the presence of BDNF, EGF receptor, and Trk-B immunoreactivity in subsets of cultured taste cells in vitro. EGF at 10 ng/mL increased the proliferation rate of cultured rat taste cells in 1- and 2-week-old cells. No treatment altered the proliferation rate at 4 weeks. Staining with bromodeoxyuridine (BrdU) and gustducin antibodies demonstrated differentiation in a subset of taste cells, indicating that a 10-ng concentration each of EGF and BDNF increased BrdU and gustducin immunoreactive cell numbers at 1 and 2 weeks. Conclusion: Our data suggest that EGF and BDNF induced not only taste cell proliferation but also differentiation without requiring nerve innervation.

BDNF and GAP43 contribute to dynamic transhemispheric functional reorganization in rat brain after contralateral C7 root transfer following brachial plexus avulsion injuries

It is known that contralateral seventh cervical nerve (C7) root transfer after brachial plexus avulsion injuries (BPAI) causes interhemispheric cortical functional reorganization. However, the potential mechanisms and the role of neurotrophic factors and/or growth-associated protein expression in the process of cerebral reorganization are not well understood. The present study identified the expression of brain-derived neurotrophic factor (BDNF) and growth-associated protein 43 (GAP43) mRNA in primary motor cortex after contralateral C7 root transfer following BPAI. BDNF and GAP43 mRNA levels were significantly increased in brain samples at both 6 and 9 months after contralateral C7 root transfer following BPAI, in comparison with the samples from the rats with BPAI only. These findings indicate that BDNF and GAP43 may play an important role during the dynamic transhemispheric functional reorganization.

The role of neurotrophic factors in autism

Autism spectrum disorders (ASDs) are pervasive developmental disorders that frequently involve a triad of deficits in social skills, communication and language. For the underlying neurobiology of these symptoms, disturbances in neuronal development and synaptic plasticity have been discussed. The physiological development, regulation and survival of specific neuronal populations shaping neuronal plasticity require the so-called 'neurotrophic factors' (NTFs). These regulate cellular proliferation, migration, differentiation and integrity, which are also affected in ASD. Therefore, NTFs have gained increasing attention in ASD research. This review provides an overview and explores the key role of NTFs in the aetiology of ASD. We have also included evidence derived from neurochemical investigations, gene association studies and animal models. By focussing on the role of NTFs in ASD, we intend to further elucidate the puzzling aetiology of these conditions.

The physiology of neural injury and regeneration: The role of neurotrophic factors

Injured nerves regenerate slowly and often over long distances. Prolonged periods for regenerating nerves to make functional connections with denervated targets prolong the period of isolation of the neurons from the target (chronic axotomy) and of the denervation of Schwann cells in the distal nerve pathways (chronic denervation). In an animal model, we demonstrated that prolonged axotomy and chronic denervation severely reduce the regenerative capacity of neurons to less to 10%. Concurrent reduction in neurotrophic factors, including brain- and glial-derived neurotrophic factors (BDNF and GDNF) in axotomized neurons and denervated Schwann cells, suggest that these factors are required to sustain nerve regeneration. Findings that exogenous BDNF and GDNF did not increase numbers of neurons that regenerate their axons in freshly cut and repaired rat nerves, but did increase the numbers significantly after chronic axotomy, are consistent with the view that there is sufficient endogenous neurotrophic factor supply in axotomized motoneurons and denervated Schwann cells to support nerve regeneration but that the reduced supply must be supplemented when target reinnervation is delayed. In addition, findings that BDNF is essential for the effectiveness of brief low frequency electrical stimulation in promoting nerve growth, provides further support for a central role of BNDF in motor nerve regeneration. Learning outcomes: Readers of this article will gain an understanding of the basis for poor functional outcomes of peripheral nerve injuries, even when surgical repair is possible.

Protection of SNpc neurons by water soluble CoQ10 in a paraquat induced rat model of Parkinson's disease: The role of neurotrophic factors

Parkinson's disease (PD) is a common neurodegenerative disorder that results from the progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). Studies show that mitochondrial dysfunction/oxidative stress is a major contributor to this disease. Currently there is no treatment to halt the progression of PD. Recently we have shown that water‐soluble coenzyme Q10 (WS‐CoQ10, NRC technology licensed to Zymes LLC) prevents the loss of dopaminergic neurons in the SNpc and ameliorates the symptoms of paraquat (PQ)‐inducted PD in the rat model. We have observed that there is activation of astroglia in the brains of WS‐CoQ10 treated animals. Whether this activation plays a role in protecting SNpc neurons is unknown. It is possible that activated astroglia cells produce neurotrophic factors that may protect neurons under oxidative stress. We analyzed brain tissue samples from PQ treated PD rats fed with either placebo or WS‐CoQ10 for DA neurons, activation of astroglia and levels of various neurotrophic growth factors. We observed significant protection of DA neurons in the SNpc, activated astroglia and increased levels of BDNF and GDNF in WS‐CoQ10 fed rats. These results indicate that WS‐CoQ10 treatment could activate astroglia that produce high levels of BDNF and GDNF and could provide protection to the DA neurons against PQ toxicity and may be used to halt PD progression.Funded by CIHR.