Brain-derived Neurotrophic Factor Enhancement Research Articles

The protective effects of repetitive transcranial magnetic stimulation with different high frequencies on motor functions in MPTP/probenecid induced Parkinsonism mouse models.

High-frequency repeated transcranial magnetic stimulation (rTMS) stimulating the primary motor cortex (M1) is an alternative, adjunctive therapy for improving the motor symptoms of Parkinson's disease (PD). However, whether the high frequency of rTMS positively correlates to the improvement of motor symptoms of PD is still undecided. By controlling for other parameters, a disease animal model may be useful to compare the neuroprotective effects of different high frequencies of rTMS. The current exploratory study was designed to compare the protective effects of four common high frequencies of rTMS (5, 10, 15, and 20Hz) and iTBS (a special form of high-frequency rTMS) and explore the optimal high-frequency rTMS on an animal PD model. Following high frequencies of rTMS application (twice a week for 5weeks) in a MPTP/probenecid-induced chronic PD model, the effects of the five protocols on motor behavior as well as dopaminergic neuron degeneration levels were identified. The underlying molecular mechanisms were further explored. We found that all the high frequencies of rTMS had protective effects on the motor functions of PD models to varying degrees. Among them, the 10, 15, and 20Hz rTMS interventions induced comparable preservation of motor function through the protection of nigrostriatal dopamine neurons. The enhancement of brain-derived neurotrophic factor (BDNF), dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT-2)and the suppression of TNF-α and IL-1β in the nigrostriatum were involved in the process. The efficacy of iTBS was inferior to that of the above three protocols. The effect of 5Hz rTMS protocol was weakest. Combined with the results of the present study and the possible side effects induced by rTMS, we concluded that 10Hz might be the optimal stimulation frequency for preserving the motor functions of PD models using rTMS treatment.

Therapeutic potential of Zataria multiflora: A narrative review of current evidence

Zataria multiflora Boiss is a perennial plant with a wide spectrum of biological and pharmacological activities including antidiabetic, anti-nociceptive, anti-asthmatic, anti-fever, anti-spastic, anti-oxidative, anti-inflammatory, and antimicrobial properties. This paper reviews the therapeutic effects of Zataria multiflora based on recent reports. The relevant reports were extracted by checking the electronic databases including PubMed, Scopus, Web of Science, and Google Scholar from the beginning of 2010 until the end of May 2023. The neuroprotective effects of Zataria multiflora can be attributed to inhibition of acetylcholinesterase, enhancement of brain-derived neurotrophic factor, and alleviation of brain oxidative damage. Zataria multiflora also exerts its protective effects on the respiratory system, liver, and kidney by reducing the level of inflammatory cytokines, scavenging the free radicals, and augmenting the antioxidant enzymes. Additionally, Zataria multiflora accelerates wound healing via upregulating transforming growth factor-β, insulin-like growth factor 1, fibroblast growth factor 2, and vascular endothelial growth factor, and inducing angiogenesis and collagen biosynthesis. Overall, the protective impacts of Zataria multiflora on different organs are mainly attributed to its antioxidant and anti-inflammatory properties.

Modulation of Neurochemical Homeostasis and Enhancement of Brain Derived-neurotrophic Factor Associated with Reversal Effects of Geraniol in Mice Exposed to Ketamine-induced Schizophrenia-like Behavior

Modulation of Neurochemical Homeostasis and Enhancement of Brain Derived-neurotrophic Factor Associated with Reversal Effects of Geraniol in Mice Exposed to Ketamine-induced Schizophrenia-like Behavior

A review for the pharmacological effects of paeoniflorin in the nervous system.

Paeoniflorin, a terpenoid glycoside compound extracted from Paeonia lactiflora Pall, shows preventive and therapeutic effects in various types of nervous system disorders. However, to date, no comprehensive knowledge on the pharmacological effects of paeoniflorin on the nervous system is available online. Clarification of this issue may be useful for the development of paeoniflorin as a new drug for the treatment of nervous system disorders. To this end, the authors summarize the pharmacological aspects of paeoniflorin and its possible mechanisms, such as restoration of mitochondrial function; inhibition of neuroinflammation, oxidative stress, and cellular apoptosis; activation of adenosine A1 receptor, cAMP response element-binding protein (CREB) and extracellular signal-regulated kinase 1/2 (ERK1/2); or enhancement of brain-derived neurotrophic factor and serotonin function, in the prevention of disorders such as cerebral ischemia, subarachnoid hemorrhage, vascular dementia, Alzheimer’s disease, Parkinson’s disease, depression, post-traumatic syndrome disorder, and epilepsy, by reviewing the previously published literature.

Hesperidin Preserves Cognitive Functions and Hippocampus Histological Architecture in Albino Wistar Rats Subjected to Stress Through Enhancement of Brain-Derived Neurotrophic Factor.

Hesperidin (HSD) is a natural compound with antioxidant potential. On the other hand, chronic stress had been linked to impaired cognitive functions as it affects many neurotransmitters and brain regions such as the hippocampus. The current study was conducted to examine the effect of HSD on learning and memory after chronic mild stress. Albino Wistar rats were subjected to chronic mild stress with HSD administered as supplements. HSD was found to decrease hippocampal amyloid beta and malondialdehyde levels, in addition, to preserve cognitive functions together with preserving hippocampus histological architecture. In conclusion, the present study sheds the light on the potential of HSD to ameliorate the deleterious effects of chronic mild stress on cognitive functions through brain-derived neurotrophic factor enhancement and reduction in Aβ formation in addition to activation of the antioxidant pathway.

Protective effects of low-intensity pulsed ultrasound on aluminum overload-induced cerebral damage through epigenetic regulation of brain-derived neurotrophic factor expression.

In consideration of its noninvasive administration and endogenous stimulation property, the enhancement of brain-derived neurotrophic factor (BDNF) via low-intensity pulsed ultrasound (LIPUS) could be a novel strategy for aluminum (Al) overload-induced cerebral damage. LIPUS was pre-treated 7 days before concomitantly given with aluminum chloride (AlCl3) daily for a period of 42 days. Morris water maze and elevated plus maze were performed to analyze spatial learning and memory. Western Blot and immunoprecipitation were used to detect BDNF and histone acetylation of histone H3 lysine 9 (H3K9) and histone H4 lysine 12 (H4K12) in the hippocampus. Assay of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-Px) indicated the extent of oxidative damages. Aluminium exposure in rats can cause attenuated spatial learning and memory, followed by up-regulated histone deacetylase 6 (HDAC6) expression, down-regulated H3K9 and H4K12 acetylation at the PIII and PIV promoter of BDNF, all of which will eventually inhibit BDNF expression. LIPUS can recover reduced cognitive function by restoring histone acetylation and BDNF expression, accompanied with increased SOD, GSH, and GSH-Px activity. LIPUS treatment might alleviate aluminium exposure-induced cognitive decline by acetylation regulation of BDNF expression and reducing oxidative stress in the hippocampus.

Tacrine(10)-Hupyridone Prevents Post-operative Cognitive Dysfunction via the Activation of BDNF Pathway and the Inhibition of AChE in Aged Mice.

Post-operative cognitive dysfunction (POCD) could cause short-term or long-term cognitive disruption lasting weeks or months after anesthesia and surgery in elderly. However, no effective treatment of POCD is currently available. Previous studies indicated that the enhancement of brain-derived neurotrophic factor (BDNF) expression, and the elevation the cholinergic system, might be effective to prevent POCD. In this study, we have discovered that tacrine(10)-hupyridone (A10E), a novel acetylcholinesterase (AChE) inhibitor derived from tacrine and huperzine A, could prevent surgery-induced short-term and long-term impairments of recognition and spatial cognition, as evidenced by the novel object recognition test and Morris water maze (MWM) tests, in aged mice. Moreover, A10E significantly increased the expression of BDNF and activated the downstream Akt and extracellular regulated kinase (ERK) signaling in the surgery-treated mice. Furthermore, A10E substantially enhanced choline acetyltransferase (ChAT)-positive area and decreased AChE activity, in the hippocampus regions of surgery-treated mice, indicating that A10E could prevent surgery-induced dysfunction of cholinergic system, possibly via increasing the synthesis of acetylcholine and the inhibition of AChE. In conclusion, our results suggested that A10E might prevent POCD via the activation of BDNF pathway and the inhibition of AChE, concurrently, in aged mice. These findings also provided a support that A10E might be developed as a potential drug lead for POCD.

Neuroprotective effect of Asparagus racemosus root extract via the enhancement of brain-derived neurotrophic factor and estrogen receptor in ovariectomized rats

Ethnopharmacological relevanceAsparagus racemosus (AR) is well known as an Ayurvedic rasayana which used traditionally by Ayurvedic practitioners for nervous disorders and prevent aging. In our previous study it was found that ethanol AR root extract can improve learning and memory impairment, induced by an ovariectomy, but the extract's mechanisms as a neuroprotective property are still unknown. Aim of the studyThis study aimed to examine the effects and mechanisms of ethanol AR root extract on the alteration of brain-derived neurotrophic factor (BDNF) and estrogen receptor (ER) subtypes in ovariectomized (OVX) rats. Materials and methodsAdult female Wistar rats were divided into five groups, 4 groups underwent ovariectomy, and one group was designed to be the sham control group. Two groups were gavaged with propylene glycol for sham, and a second group similarly prepared for OVX. Two further groups of OVX rats were gavaged once daily, one group with 100 mg/kg b.w. of ethanol AR root extract and the second group with 1000 mg/kg b.w. of ethanol AR root extract. The fifth group was gavaged once daily with 0.1 mg/kg b.w. of 17α-ethynylestradiol (EE). BDNF, ERα and ERβ expression were evaluated by western blot analysis. ResultsThe western blot analysis revealed that the OVX rats showed a significant decrease in BDNF and a down-regulation of ERα and ERβ in the frontal cortex and hippocampus. It was also demonstrated that EE and AR root extract increased BDNF, ERα and ERβ in the frontal cortex and hippocampus of ovariectomized rats. ConclusionsBased on these results, the enhancement of BDNF and ERs up-regulation may be involved in the neuroprotective effects of ethanol AR root extract in ovariectomized rat.

Integral Characterization of Defective BDNF/TrkB Signalling in Neurological and Psychiatric Disorders Leads the Way to New Therapies.

Enhancement of brain-derived neurotrophic factor (BDNF) signalling has great potential in therapy for neurological and psychiatric disorders. This neurotrophin not only attenuates cell death but also promotes neuronal plasticity and function. However, an important challenge to this approach is the persistence of aberrant neurotrophic signalling due to a defective function of the BDNF high-affinity receptor, tropomyosin-related kinase B (TrkB), or downstream effectors. Such changes have been already described in several disorders, but their importance as pathological mechanisms has been frequently underestimated. This review highlights the relevance of an integrative characterization of aberrant BDNF/TrkB pathways for the rational design of therapies that by combining BDNF and TrkB targets could efficiently promote neurotrophic signalling.

Recovery of motor coordination after exercise is correlated to enhancement of brain-derived neurotrophic factor in lactational vanadium-exposed rats

Lactational exposure to vanadium can reduce the locomotor activity in adult animals. In this study, we investigated whether lactational vanadium exposure impairs the motor coordination and whether exercise ameliorates this dysfunction. Sprague–Dawley dams were treated with or without vanadium during lactation. The weaned male offspring were trained to treadmill running for 5 weeks and then examined their motor coordination on a rotarod. The neuroprotective effect of exercise was evaluated by the brain-derived neurotrophic factor (BDNF) in plasma and cerebellum. The results demonstrated that vanadium-exposed rats exhibited impaired motor coordination and reduced plasma and cerebellar BDNF levels. Treadmill running during childhood-adolescence prevented the impaired motor coordination in the lactational vanadium-exposed rats. The beneficial effect of treadmill running on motor coordination in the vanadium-exposed rats was correlated to the normalization of plasma and cerebellar BDNF levels, as well as the increased TrkB phosphorylation in the cerebellum. The result suggests that exercise may prevent the impairment of motor coordination in the lactational vanadium-exposed rats.

Rapid Antidepressant Activity of Ethanol Extract of Gardenia jasminoides Ellis Is Associated with Upregulation of BDNF Expression in the Hippocampus.

Ethanol extract of Yueju pill, a Traditional Chinese Medicine herbal formula widely used to treat mood disorders, demonstrates rapid antidepressant effects similar to ketamine, likely via instant enhancement of brain-derived neurotrophic factor (BDNF) expression in the hippocampus. Here we investigated ethanol extracts of the constituent herbs of Yueju responsible for rapid antidepressant effects. Screening with tail suspension test in Kunming mice at 24 hours after a single administration of five individual constituent herbs of Yueju, we found that only Gardenia jasminoides Ellis (GJ) showed a significant effect. The antidepressant response started at 2 hours after GJ administration. Similar to Yueju and ketamine, a single administration of GJ significantly reduced the number of escape failures in the learned helplessness test. Furthermore, GJ decreased latency of food consumption in the novelty suppressed-feeding test. Additionally, starting from 2 hours and continuing for over 20 hours after GJ administration, BDNF expression in the hippocampus was upregulated, temporally linked with the antidepressant response. These findings suggest that GJ has rapid antidepressant effects, which are associated with the elevated expression of BDNF in the hippocampus. In Yueju formula, Yue represents GJ, as thus our study demonstrates the primary role of GJ in rapid antidepressant efficacy of Yueju.

The role of RIM1α in BDNF-enhanced glutamate release

Brain-derived neurotrophic factor (BDNF) is known to activate proline-directed Ser/Thr protein kinases and to enhance glutamatergic transmission via a Rab3a-dependent molecular pathway. The identity of molecular targets in BDNF's action on Rab3a pathway, a synaptic vesicle protein involved in vesicle trafficking and synaptic plasticity, is not fully known. Here we demonstrate that BDNF enhances depolarization-evoked efflux of [ 3H]-glutamate from nerve terminals isolated from the CA1 region of the hippocampus. BDNF also potentiated hyperosmotic shock-evoked [ 3H]-glutamate efflux, indicating an effect on the size of the readily releasable pool. This effect of BDNF was completely abolished in nerve terminals derived from Rim1αKO (Rab3 interacting molecule 1α null mutant) mice. Using in vitro phosphorylation assays we identified two novel phosphorylation sites, Ser447 and Ser745 that were substrates for ERK2, a proline-directed kinase known to be activated by BDNF. The pSer447 site was phosphorylated under resting conditions in hippocampal CA1 nerve terminals and its phosphorylation was enhanced by BDNF treatment, as indicated by the use of a pSer447-RIM1α antibody we have developed. Together these findings identify RIM1α, a component of the Rab3a molecular pathway in mediating presynaptic plasticity, as a necessary factor in BDNF's enhancement of [ 3H]-glutamate efflux from hippocampal CA1 nerve terminals and indicate a possible role for RIM1α phosphorylation in BDNF-dependent presynaptic plasticity.