Brain‐derived neurotrophic factor is upregulated in the cervical dorsal root ganglia and spinal cord and contributes to the maintenance of pain from facet joint injury in the rat

The facet joint is commonly associated with neck and low back pain and is susceptible to loading‐induced injury. Although tensile loading of the cervical facet joint has been associated with inflammation and neuronal hyperexcitability, the mechanisms of joint loading‐induced pain remain unknown. Altered brain‐derived neurotrophic factor (BDNF) levels are associated with a host of painful conditions, but the role of BDNF in loading‐induced joint pain remains undefined. Separate groups of rats underwent a painful cervical facet joint distraction or a sham procedure. Bilateral forepaw mechanical hypersensitivity was assessed and BDNF mRNA and protein levels were quantified in the dorsal root ganglion (DRG) and spinal cord at days 1 and 7. Facet joint distraction induced significant (P < 0.001) mechanical hypersensitivity at both time points. Painful joint distraction did not alter BDNF mRNA in the DRG compared with sham levels but did significantly increase (P < 0.016) BDNF protein expression over sham in the DRG at day 7. Painful distraction also significantly increased BDNF mRNA (P = 0.031) and protein expression (P = 0.047) over sham responses in the spinal cord at day 7. In a separate study, intrathecal administration of the BDNF‐sequestering molecule trkB‐Fc on day 5 after injury partially attenuated behavioral sensitivity after joint distraction and reduced pERK in the spinal cord at day 7 (P < 0.045). Changes in BDNF after painful facet joint injury and the effect of spinal BDNF sequestration in partially reducing pain suggest that BDNF signaling contributes to the maintenance of loading‐induced facet pain but that additional cellular responses are also likely involved. © 2013 Wiley Periodicals, Inc.     

Use it and boost it with physical and mental activity

One of the now classic tenets of neuroscience is that the brain retains a substantial amount of structural and functional plasticity throughout adulthood and old age. Enriching experiences that stimulate physical and mental activity produce robust changes in subsequent behaviors, including learning and memory, that tap a wide range of neural systems. In this article, we review evidence for cognitive priming with physical and mental exercise through a memory systems lens and present brain‐derived neurotrophic factor (BDNF) signaling as one candidate neural mechanism for experience‐dependent modulation of learning and memory. We highlight our recent findings showing that priming with voluntary exercise or with spontaneous alternation, a working memory task, enhances new learning of hippocampus‐sensitive place, or striatum‐sensitive response tasks. Blocking BDNF signaling with infusions of a BDNF receptor inhibitor into hippocampus or striatum just before training on place or response tasks, respectively, abrogated the benefits of priming regardless of the type of priming experience. These results suggest that enhanced BDNF signaling during learning may itself produce the cognitive benefits afforded by prior physical or mental activity. © 2013 Wiley Periodicals, Inc.     

Neurotrophin gene expression in rat brain under the action of Semax, an analogue of ACTH 4-10

The heptapeptide Semax, an analogue of the N-terminal adrenocorticotropic hormone fragment (4-10) (ACTH(4-10)), has been shown to exert a number of neuroprotective effects. There are some investigations that connected these effects with the increase of neurotrophin gene expression under the peptide drug application in neuron cell cultures [M.I. Shadrina, O.V. Dolotov, I.A. Grivennikov, P.A. Slominsky, L.A. Andreeva, L.S. Inozemtseva, S.A. Limborska, N.F. Myasoedov, Rapid induction of neurotrophin mRNAs in rat glial cell cultures by Semax, an adrenocorticotropic hormone analogue, Neurosci. Lett. 308 (2001) (2) 115-118]. In this work, we examined the action of Semax on rapid changes of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) gene expression in vivo. Male Wistar rats were treated for 1h with Semax (50 microg/kg, single intranasal application) and neurotrophin gene expression in rat brain was analyzed by real-time polymerase chain reaction (PCR). It was revealed that an intranasal application of Semax increased the expression of both neurotrophin genes in rat hippocampus. Bdnf gene expression also increased in the brainstem and cerebellum. Ngf gene expression decreased in rat frontal cortex. Thus, Semax induces rapid, gene- and region-specific changes in neurotrophin gene expression in normal rat brain.     

BDNF tagging polymorphisms and haplotype analysis in sporadic Parkinson's disease in diverse ethnic groups

Experimental and clinical data suggest that genetic variations in brain-derived neurotrophic factor (BDNF) gene may affect risk for Parkinson's disease (PD). We performed a case-control association analysis of BDNF in three independent Caucasian cohorts (Greek, North American, and Finnish) of PD using eight tagging SNPs and five constructed haplotypes. No statistically significant differences in genotype and allele frequencies were found between cases and controls in all series. A relatively rare BDNF haplotype showed a trend towards association in the Greek (p=0.02) and the Finnish (p=0.03) series (this haplotype was not detected in the North American series). However, given the large number of comparisons these associations are considered non-significant. In conclusion, our results do not provide statistically significant evidence that common genetic variability in BDNF would associate with the risk for PD in the Caucasian populations studied here.     

Tinnitus behavior and hearing function correlate with the reciprocal expression patterns of BDNF and Arg3.1/arc in auditory neurons following acoustic trauma

The molecular changes following sensory trauma and the subsequent response of the CNS are poorly understood. We focused on finding a molecular tool for monitoring the features of excitability which occur following acoustic trauma to the auditory system. Of particular interest are genes that alter their expression pattern during activity-induced changes in synaptic efficacy and plasticity. The expression of brain-derived neurotrophic factor (BDNF), the activity-dependent cytoskeletal protein (Arg3.1/arc), and the immediate early gene c-Fos were monitored in the peripheral and central auditory system hours and days following a traumatic acoustic stimulus that induced not only hearing loss but also phantom auditory perception (tinnitus), as shown in rodent animal behavior models. A reciprocal responsiveness of activity-dependent genes became evident between the periphery and the primary auditory cortex (AI): as c-Fos and BDNF exon IV expression was increased in spiral ganglion neurons, Arg3.1/arc and (later on) BDNF exon IV expression was reduced in AI. In line with studies indicating increased spontaneous spike activity at the level of the inferior colliculus (IC), an increase in BDNF and GABA-positive neurons was seen in the IC. The data clearly indicate the usefulness of Arg3.1/arc and BDNF for monitoring trauma-induced activity changes and the associated putative plasticity responses in the auditory system.     

Protective effect of ginsenoside Rh2 on scopolamine‐induced memory deficits through regulation of cholinergic transmission,oxidative stress and the ERK‐CREB‐BDNF signaling pathway

Rh2 is a rare ginsenoside and there are few reports of its effect on cognition compared with other similar molecules. This study aimed to establish the impact of Rh2 treatment on improving scopolamine (Scop)‐induced memory deficits in mice and illuminate the underlying mechanisms. First, memory‐related behavior was evaluated using two approaches: object location recognition (OLR), based on spontaneous activity, and a Morris water maze (MWM) task, based on an aversive stimulus. Our results suggested that Rh2 treatment effectively increased the discrimination index of the mice in the OLR test. In addition, Rh2 elevated the crossing numbers and decreased the escape latency during the MWM task. Moreover, Rh2 markedly upregulated the phosphorylation of the extracellular signal‐regulated kinase (ERK)‐cAMP response element binding (CREB)‐brain derived neurotrophic factor (BDNF) pathway in the hippocampus. Meanwhile, the administration of Rh2 significantly promoted the cholinergic system and dramatically suppressed oxidative stress in the hippocampus. Taken together, Rh2 exhibited neuroprotective effects against Scop‐induced memory dysfunction in mice. Rh2 activity might be ascribed to several underlying mechanisms, including its effects on modulating the cholinergic transmission, inhibiting oxidative stress and activating the ERK‐CREB‐BDNF signaling pathway. Consequently, the ginsenoside Rh2 might serve as a promising candidate compound for Alzheimer's disease.     

RS 10767664 gene variant in Brain Derived Neurotrophic Factor (BDNF) affect metabolic changes and insulin resistance after a standard hypocaloric diet

Background

Role of BDNF variants on change in body weight and cardiovascular risk factors after weight loss remains unclear in obese patients.

Dominant negative DISC1 mutant mice display specific social behaviour deficits and aberration in BDNF and cannabinoid receptor expression

Objectives. Disrupted in schizophrenia 1 (DISC1) is considered the most prominent candidate gene for schizophrenia. In this study, we aimed to characterize behavioural and brain biochemical traits in a mouse expressing a dominant negative DISC1mutant (DN-DISC1). Methods. DN-DISC1 mice underwent behavioural tests to evaluate object recognition, social preference and social novelty seeking. ELISA was conducted on brain tissue to evaluate BDNF levels. Western blot was employed to measure BDNF receptor (TrkB) and cannabinoid receptor CB1. Results. The mutant DISC1 mice displayed deficits in preference to social novelty while both social preference and object recognition were intact. Biochemical analysis of prefrontal cortex and hippocampus revealed a modest reduction in cortical TrkB protein levels of male mice while no differences in BDNF levels were observed. We found sex dependent differences in the expression of cannabinoid-1 receptors. Conclusions. We describe novel behavioural and biochemical abnormalities in the DN-DISC1 mouse model of schizophrenia. The data shows for the first time a possible link between DISC1 mutation and the cannabinoid system.