Doses Of Brain-derived Neurotrophic Factor Research Articles

Effects of brain-derived neurotrophic factor (BDNF) on the Schizophrenia model of animals

BackgroundSchizophrenia（SCZ）is a common clinically chronic psychiatric disease, and there have no effective specific therapeutic drugs in clinical practice currently. Studies have shown that the expression level of brain-derived neurotrophic factor (BDNF) in schizophrenics has decreased, so the expression level of BDNF has always been one of the evaluation indicators of SCZ. The neurotrophic factor hypothesis believes that increase or decrease of the expression level of BDNF may be one of the pathophysiological basis of SCZ. MethodsIn this study, schizophrenic mice model with MK-801-induced glutamate dysfunction was established, and two doses of BDNF were administered to schizophrenic mice by intranasal administration. The four groups of mice: Control group, Model group, BDNF-20, BDNF-100 performed a series of behavioral tests to explore the effects of BDNF on sensory motor gating, anxiety, depression, social interaction, spontaneous activity, and memory in schizophrenic mice. Transcriptome sequencing of the BDNF high group and Model group in prefrontal cortex and hippocampus, using Metascape for gene function annotation and enrichment pathway analysis, to obtain BDNF transcription regulation information, understand the molecular mechanism of BDNF in SCZ further. Subsequently，immunofluorescence detected the effects of BDNF on neurons and glial cells in the prefrontal cortex and hippocampus. ConclusionThe results show that BDNF can improve the behavior of SCZ by regulating the construction of the nervous system, affecting the growth and distribution of neurons and glial cells, and changing inflammation and apoptosis in the brain.

Enhancement of Motor Function Recovery after Spinal Cord Injury in Mice by Delivery of Brain-Derived Neurotrophic Factor mRNA

Spinal cord injury (SCI) is a debilitating condition that can cause impaired motor function or full paralysis. In the days to weeks following the initial mechanical injury to the spinal cord, inflammation and apoptosis can cause additional damage to the injured tissues. This secondary injury impairs recovery. Brain-derived neurotrophic factor is a secreted protein that has been shown to improve a variety of neurological conditions, including SCI, by promoting neuron survival and synaptic plasticity. This study treated a mouse model of contusion SCI using a single dose of brain-derived neurotrophic factor (BDNF) mRNA nanomicelles prepared with polyethylene glycol polyamino acid block copolymer directly injected into the injured tissue. BDNF levels in the injured spinal cord tissue were approximately doubled by mRNA treatment. Motor function was monitored using the Basso Mouse Scale and Noldus CatWalk Automated Gait Analysis System for 6 weeks post-injury. BDNF-treated mice showed improved motor function recovery, demonstrating the feasibility of mRNA delivery to treat SCI.

Brain-Derived Neurotrophic Factor: Effects on Genetically and Epigenetically Determined Behavioral Disorders

Studies in recent years have significantly widened our understanding of the mechanism of action of brain-derived neurotrophic factor (BDNF) and the potential areas of its application. This review presents results from our own studies, along with published data on the influences of BDNF on epigenetically and genetically determined behavioral disorders. Particular attention is paid to the role of the genotype and the involvement of the brain serotonin system in the effects of BDNF. The material presented in this review provides evidence that: 1) the key genes of the brain serotonin system (tryptophan hydroxylase 2, 5-HT1A and 5-HT2A receptors) are involved in the mechanism of action of BDNF; 2) single central doses of BDNF have long-lasting positive influences on several genetically determined manifestations of pathological behavior; 3) BDNF can weaken the manifestations of behavioral disorders induced by harmful environmental factors acting during the prenatal period.

Effect of brain-derived neurotrophic factor on c-jun expression in the rd mouse retina.

To determine the location of c-jun protein, dynamic changes in c-jun mRNA and protein expression, and ultrastructure characteristics in the rd mouse retina, following a single dose of brain-derived neurotrophic factor (BDNF) in a short period of time. A single intravitreal injection of BDNF at two dosages (25µg/L or 50µg/L) was given to the right eye of the rd mouse at age 2 and 3 weeks respectively. Two weeks after injection, the location of c-jun protein in the retina was observed by immunofluorescence detection, c-jun mRNA and protein expression in retinas were detected by quantitative real time polymerase chain reaction (RT-PCR) and western immunoblotting analysis, ultrastructure characteristics of retinas were detected by transmission electron microscope (TEM) observation. c-jun protein was expressed in the inner nuclear layer (INL) of retina. BDNF at two dosages (25µg/L and 50µg/L) increased c-jun mRNA expression at PN-4 weeks respectively (P(1)=0.019, P(2)=0.021). 50µg/L BDNF increased c-jun protein expression at PN-4 weeks (P =0.000). The retinal ultrastructure was improved. The effects of BDNF exerts on the c-jun expression in the retina are dose-dependent and time-dependent, which may mediate photoreceptor rescue indirectly in the pathological process of retinitis pigmentosa (RP) at early stage.

BDNF as otoprotectant in toxin-induced hearing loss

Conclusion: Brain-derived neurotrophic factor (BDNF) can prevent auditory brainstem response (ABR) threshold shift changes caused by Pseudomonas aeruginosa exotoxin A (PaExoA). Objective: Peptides of the neurotrophin family are known to prevent neuronal death during embryonic development by interacting with specific membrane receptors. The purpose of this study was to investigate whether a single dose of BDNF is an effective protectant against toxic effects of PaExoA-induced ABR threshold shifts. Materials and Methods: Eight groups of Sprague-Dawley rats were used. There were five control groups (n = 20) as follows. Group A (n = 4) received NaCl solution; group B (n = 3) received 4 µg BDNF; group C (n = 4) received 1 μg/20 μl PaExoA; group D (n = 4) received 2 μg/20 μl PaExoA; group E (n = 5) received 10 µg/20 µl PaExoA injected into the round window niche. Three treatment groups (n = 13) received a single dose of PaExoA and 4 µg of BDNF simultaneously. Group 1 (n = 3) received 1 μg/20 μl PaExoA + 4 µg of BDNF; group 2 (n = 5) received 2 μg/20 μl PaExoA + 4 µg BDNF; group 3 (n = 5) received 10 μg/20 μl PaExoA + 4 µg BDNF. ABR was used to measure efficacy by analyzing threshold shifts before and after injections. Results: A single dose of BDNF prevented changes in ABR thresholds following exposure to increasing concentrations of PaExoA injected into the middle ear.

Early hearing protection by brain-derived neurotrophic factor

Conclusion: Brain-derived neurotrophic factor (BDNF) protects the inner ear from PaExoA (exotoxin A from Pseudomonas aeruginosa)-induced sensory neural hearing loss when administered 12 h after exotoxin, but not after 72 h. Objective: BDNF is a peptide in the neurotrophin family with protective effects against noise-induced hair cell loss and toxic inner ear damage following exposure to cisplatin. The exotoxin A (PaExoA) from P. aeruginosa, the most common microorganism in chronic suppurative otitis media, induces sensorineural hearing loss in rats. Previous study showed that, when given simultaneously with the exotoxin, BDNF protected the inner ear from damage. The aim of this study was to determine if BDNF has a protective effect when given 12–72 h after PaExoA. Materials and Methods : Five groups of Sprague-Dawley rats were used. The three control groups (n = 16) were as follows. Group 1 (n = 8) received 15 µg/20 µl PaExoA; group 2 (n = 5) received 20 µg/20 µl PaExoA; and group 3 (n = 3) received 25 µg/20 µl PaExoA injected into the round window niche. There were two treatment groups (n = 12): group A (n = 6) received 15 µg/20 µl PaExoA and 4 µg/20 µl BDNF 12 h later; group B (n = 6) received 15 µg/20 µl PaExoA and 4 µg/20 µl BDNF 72 h later. Brainstem response audiometry (ABR) was performed on day 0 (control), and repeated on days 7, 14, 21, 28, and 35 to analyze the thresholds shifts. Results: Exposure to 15 µg/20 µl PaExoA caused persistent and significant ABR impairment in controls when measured after 35 days. A single dose of BDNF given 12 h after PaExoA reduced hearing loss significantly, but when BDNF was given 72 h after PaExoA no protective effect was evident.

Brain-derived neurotrophic factor (BDNF) mediates bone morphogenetic protein-2 (BMP-2) effects on cultured striatal neurones.

Bone morphogenetic proteins are members of the transforming growth factor-beta superfamily that have multiple functions in the developing nervous system. One of them, bone morphogenetic protein-2 (BMP-2), promotes the differentiation of cultured striatal neurones, enhancing dendrite growth and calbindin-positive phenotype. Bone morphogenetic proteins have been implicated in cooperative interactions with other neurotrophic factors. Here we examined whether the effects of BMP-2 on cultured striatal neurones are mediated or enhanced by other neurotrophic factors. BMP-2 had a cooperative effect with low doses of brain-derived neurotrophic factor or neurotrophin-3 (but not with other neurotrophic factors such as glial cell line-derived neurotrophic factor, neurturin or transforming growth factor-beta 2) on the number of calbindin-positive striatal neurones. Moreover, BMP-2 induced phosphorylated Trk immunoreactivity in cultured striatal neurones, suggesting that neurotrophins are involved in BMP-2 neurotrophic effects. The addition of TrkB-IgG or antibodies against brain-derived neurotrophic factor abolished the effects of BMP-2 on the number and degree of differentiation of calbindin-positive striatal neurones. Indeed, BMP-2 treatment increased brain-derived neurotrophic factor protein levels in treated cultures media and BDNF immunocytochemistry revealed that this neurotrophin was produced by neuronal cells. Taken together, these results indicate that brain-derived neurotrophic factor mediates the effects of BMP-2 on striatal neurones.

Long-term effects of a single dose of brain-derived neurotrophic factor on motoneuron survival following spinal root avulsion in the adult rat

The long-term effect of a single dose of Brain-derived neurotrophic factor (BDNF) treatment on adult motoneuron survival and on expression of nitric oxide synthase (NOS) following nerve injury (avulsion) was investigated and compared with that of continuous BDNF treatment. By 6 weeks post-injury, more than 80% of motoneurons survived in animals treated with either a single dose or continuous treatment of BDNF, while only 30% of motoneurons survived in control animals (avulsion only). There were no significant differences in motoneuron survival between animals receiving a single dose and those with continuous treatment of BDNF. Additionally, the expression of NOS in avulsed motoneurons was almost completely inhibited in all BDNF treatment groups regardless of the mode of administration (single vs. continuous). These data indicate that treatment with a single dose of BDNF at the time of injury can inhibit NOS expression and provide the first evidence that in this situation BDNF has a long-term rescue effect on adult motoneuron survival after root avulsion.

Brain-derived neurotrophic factor enhances spontaneous sleep in rats and rabbits.

Various growth factors are involved in sleep regulation. Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin family; it and its receptors are found in normal brain. Furthermore, cerebral cortical levels of BDNF mRNA have a diurnal variation and increase after sleep deprivation. Therefore, we investigated whether BDNF would promote sleep. Twenty-four male Sprague-Dawley rats (320-380 g) and 25 male New Zealand White rabbits (4.5-5.5 kg) were surgically implanted with electroencephalographic (EEG) electrodes, a brain thermistor, and a lateral intracerebroventricular cannula. The animals were injected intracerebroventricularly with pyrogen-free saline and, on a separate day, one of the following doses of BDNF: 25 or 250 ng in rabbits; 10, 50, or 250 ng in rats. The EEG, brain temperature, and motor activity were recorded for 23 h after the intracerebroventricular injections. BDNF increased time spent in non-rapid eye movement sleep (NREMS) in rats and rabbits and REMS in rabbits. Current results provide further evidence that various growth factors are involved in sleep regulation.

The effects of central administration of neurotrophins or transplants of fetal tectal tissue on retinal ganglion cell survival following removal of the superior colliculus in neonatal rats

In neonatal rats, intraocular injections of brain-derived neurotrophic factor (BDNF) or neurotrophin 4/5 (NT-4/5) enhance the survival of retinal ganglion cells (RGCs) following superior colliculus (SC) ablation [Q. Cui, A.R. Harvey, At least two mechanisms are involved in the death of retinal ganglion cells following target ablation in neonatal rats, J. Neurosci., 15, 1995, pp. 8143–8155.]. The aim of the present study was to determine if: (i) fetal tectal tissue grafted into the lesion site, or (ii) neurotrophins applied centrally to the injured SC, also decreased lesion-induced RGC death. Nuclei of tectally projecting RGCs were identified by injecting diamidino yellow (DY) into the left SC of 2-day-old (P2) Wistar rats. Injected SCs were lesioned at P4. In some animals, embryonic (E16) tectal tissue was then implanted into the lesion cavity; host rats were perfused 24 h or 20 days later. In short-term (24-h) studies, the number of DY-labelled pyknotic profiles was compared to the number of normal DY-labelled RGCs in retinal wholemounts (right eyes). The proportion of dying RGCs in animals with grafts (10.7%, n=17) was not significantly different from lesion-only rats (13.2%, n=26). Nonetheless, the long-term (20-day) study showed that, in most rats, fetal tectal tissue survived in the lesion cavity and in some cases, the grafts received host retinal input. In another group, different doses of BDNF or NT-4/5 were applied to the SC after P4 tectal lesions. Rats were perfused 24 h later and the number of pyknotic vs. normal DY-labelled RGCs was determined. Initial trials in which SC lesions were filled with gelfoam soaked in BDNF or NT-4/5 were unsuccessful; however, RGC death was reduced ( p<0.05, Dunnett's test) in rats that received gelfoam implants as well as focal neurotrophin injections into SC rostral to the lesion. The lowest pyknotic rate in individual animals from the BDNF and NT-4/5 groups was 2.41% and 2.01%, respectively. Overall, the proportion of dying RGCs was 7.0% ( n=8) for BDNF and 7.4% ( n=17) for NT-4/5 treated rats. Normal RGC densities were also significantly higher in these animals. NT-4/5 topically applied to the posterior surface of the eye did not reduce RGC death. The data show that the viability of injured neonatal RGCs is increased by specific retrograde neurotrophin-mediated survival signals which can be activated from the SC.

K‐252b Potentiation of Neurotrophin‐3 Is trkA Specific in Cells Lacking p75NTR

K-252b potentiates the neurotrophic effects of neurotrophin-3 (NT-3) in primary cultures of rat central cholinergic and peripheral sensory neurons and in a rat pheochromocytoma PC12 cell line. The ligand and receptor specificity, and role of the low-affinity neurotrophin receptor (p75NTR) in the potentiation response induced by K-252b, are unknown. To address the issues of ligand and receptor specificity of K-252b potentiation, we have examined neurotrophin-induced DNA synthesis ([3H]-thymidine incorporation) in NIH3T3 cells expressing trkA, trkB, or trkC. Neither NT-3 nor K-252b alone could stimulate mitogenic activity in the trkA-overexpressing clone. However, coaddition of K-252b (EC50 of approximately 2 nM) with 10-100 ng/ml NT-3 led to incorporation of [3H]thymidine in trkA expressing cells to a level induced by optimal concentrations of nerve growth factor (NGF). The K-252b- and NT-3-induced [3H]thymidine incorporation correlated with an increase in the tyrosine autophosphorylation of the trkA receptor as well as tyrosine phosphorylation of trk-associated phospholipase C-gamma 1 and SH2-containing proteins. K-252b did not potentiate submaximal doses of NGF, or maximal doses of brain-derived neurotrophic factor (BDNF) or neurotrophin-4/5 (NT-4/ 5) in trkA-expressing cells. Furthermore, K-252b did not potentiate DNA synthesis by submaximal doses of BDNF, NT-4/5, or NT-3 in trkB- or trkC-expressing NIH3T3 cells, suggesting that the potentiation profile for K-252b was specific for NT-3 in trkA-expressing cells. We found no expression of p75NTR in the trk-expressing NIH3T3 cells. This is the first demonstration that K-252b potentiates a trkA-mediated biological nonneuronal response by NT-3 that occurs independent of p75NTR and appears to be both ligand and receptor specific.