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BDNF Expression (bdnf + expression)
Selected AbstractsChanges in alternative brain-derived neurotrophic factor transcript expression in the developing human prefrontal cortexEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2009Jenny Wong Abstract In this study, we determined when and through which promoter brain-derived neurotrophic factor (BDNF) transcription is regulated during the protracted period of human frontal cortex development. Using quantitative real-time polymerase chain reaction, we examined the expression of the four most abundant alternative 5, exons of the BDNF gene (exons I, II, IV, and VI) in RNA extracted from the prefrontal cortex. We found that expression of transcripts I,IX and VI,IX was highest during infancy, whereas that of transcript II,IX was lowest just after birth, slowly increasing to reach a peak in toddlers. Transcript IV,IX was significantly upregulated within the first year of life, and was maintained at this level until school age. Quantification of BDNF protein revealed that levels followed a similar developmental pattern as transcript IV,IX. In situ hybridization of mRNA in cortical sections showed the highest expression in layers V and VI for all four BDNF transcripts, whereas moderate expression was observed in layers II and III. Interestingly, although low expression of BDNF was observed in cortical layer IV, this BDNF mRNA low-zone decreased in prominence with age and showed an increase in neuronal mRNA localization. In summary, our findings show that dynamic regulation of BDNF expression occurs through differential use of alternative promoters during the development of the human prefrontal cortex, particularly in the younger age groups, when the prefrontal cortex is more plastic. [source] The Langerhans' cell-like cell lines XS52 and XS106 express mRNA for ciliary neurotrophic factor and neurotrophic factor 4/5EXPERIMENTAL DERMATOLOGY, Issue 9 2004K. Seiffert Neurotrophins are responsible for the survival and outgrowth of nerves within the peripheral and central nervous systems. These factors include brain-derived neurotrophic factor (BDNF), CNTF, NT 3, and NT4/5. We have previously shown that LCs lie in close proximity to nerves and that several neuropeptides regulate LC function, implying that nerves send regulatory signals to LCs. To evaluate the possibility that LC signal nerves by release of neurotrophins, we examined LC expression of neurotrophins by RT-PCR. To eliminate the possibility of contaminating keratinocytes in highly enriched LC preparations, we utilized the LC-like cell lines XS52 (BALB/c derived) and XS106 (A/J derived) for initial experiments. The RNA obtained was digested with DNase to ensure complete absence of genomic DNA. Several independent RT-PCRs revealed expression of bands of the expected size for CTNF and NT4/5, but not for BDNF and NT3 in XS106 and XS52 cells. In contrast, the transformed keratinocyte cell line PAM212 expressed BDNF, as well as CTNF and NT4/5. Preliminary experiments with purified LC confirm the expression of CTNF and NT4/5 and also show the expression of BDNF. However, we cannot be sure that BDNF expression is not due to keratinocyte contamination. We conclude that LCs may regulate nerve cells by the release of neurotrophic factors. [source] Additive effect of BDNF and REST polymorphisms is associated with improved general cognitive abilityGENES, BRAIN AND BEHAVIOR, Issue 7 2008F. Miyajima Brain-derived neurotrophic factor (BDNF) is a pleiotropic protein involved in neuronal proliferation, differentiation, synaptic plasticity and survival. Independent studies investigating association between the functional BDNF Val66Met polymorphism and cognitive abilities have reported some conflicting findings, which may reflect inadequate sample size, variation in testing methods, population stratification or the confounding effects of other genes. To test the latter hypothesis, we screened and genotyped polymorphisms in the RE1-silencing transcription factor (REST) gene whose function includes the downregulation of BDNF expression. We identified an exon 4 hexadecapeptide variable number tandem repeat (VNTR) with either four or five copies that was located within a proline-rich domain and investigated a further five single nucleotide polymorphisms (SNPs). Using a cohort of 746 community-dwelling older volunteers, we analysed REST genotype data both independently and in combination with the BDNF Val66Met polymorphism. A haplotype within the REST gene containing the four copy VNTR and a non-synonymous SNP showed a weak but significant association with a higher score of general intelligence (P = 0.05). Analysis of this haplotype and the BDNF Val66Met polymorphism in combination showed a significant interaction (global P -value = 0.0003) with an additive increase in cognitive performance for those possessing the BDNF Val66 allele and the REST haplotype containing the four copy repeat (P = 0.004). The REST haplotypes in combination with the BDNF Met66 polymorphism did not reduce cognitive performance more than the independent influence of the Met66 allele. Our results suggest that investigation of a common REST polymorphism may be necessary to help reduce contrasting reports based around BDNF Val66Met and cognition. [source] Nitric oxide regulates BDNF release from nodose ganglion neurons in a pattern-dependent and cGMP-independent mannerJOURNAL OF NEUROSCIENCE RESEARCH, Issue 6 2010Hui-ya Hsieh Abstract Activity of arterial baroreceptors is modulated by neurohumoral factors, including nitric oxide (NO), released from endothelial cells. Baroreceptor reflex responses can also be modulated by NO signaling in the brainstem nucleus tractus solitarius (NTS), the primary central target of cardiovascular afferents. Our recent studies indicate that brain-derived neurotrophic factor (BDNF) is abundantly expressed by developing and adult baroreceptor afferents in vivo, and released from cultured nodose ganglion (NG) neurons by patterns of baroreceptor activity. Using electrical field stimulation and ELISA in situ, we show that exogenous NO nearly abolishes BDNF release from newborn rat NG neurons in vitro stimulated with single pulses delivered at 6 Hz, but not 2-pulse bursts delivered at the same 6-Hz frequency, that corresponds to a rat heart rate. Application of L-NAME, a specific inhibitor of endogenous NO synthases, does not have any significant effect on activity-dependent BDNF release, but leads to upregulation of BDNF expression in an activity-dependent manner. The latter effect suggests a novel mechanism of homeostatic regulation of activity-dependent BDNF expression with endogenous NO as a key player. The exogenous NO-mediated effect does not involve the cGMP-protein kinase G (PKG) pathway, but is largely inhibited by N-ethylmaleimide and TEMPOL that are known to prevent S-nitrosylation. Together, our current data identify previously unknown mechanisms regulating BDNF availability, and point to NO as a likely regulator of BDNF at baroafferent synapses in the NTS. © 2009 Wiley-Liss, Inc. [source] NMDA receptors mediate an early up-regulation of brain-derived neurotrophic factor expression in substantia nigra in a rat model of presymptomatic Parkinson's diseaseJOURNAL OF NEUROSCIENCE RESEARCH, Issue 10 2009Gonzalo Bustos Abstract The clinical symptoms of Parkinson's disease (PD) appear late and only when the degenerative process at the level of the nigrostriatal dopamine (DA) pathway is quite advanced. An increase in brain-derived neurotrophic factor (BDNF) expression may be one of the molecular signals associated to compensatory and plastic responses occurring in basal ganglia during presymptomatic PD. In the present study, we used in vivo microdialysis, semiquantitative reverse transcriptase,polymerase chain reaction, and immunohistochemistry to study N-methyl- D -aspartic acid (NMDA) receptor regulation of BDNF expression in substantia nigra (SN) of adult rats after partial lesioning of the nigrostriatal DA pathway with unilateral striatal injections of 6-hydroxydopamine (6-OHDA). A time-dependent partial decrease of striatal DA tissue content as well as parallel and gradual increases in extracellular glutamate and aspartate levels in SN were found 1 to 7 days after unilateral 6-OHDA intrastriatal injection. Instead, the number of tyrosine hydroxylase,immunoreactive (IR) cells in the ipsilateral SN pars compacta remained statistically unchanged after neurotoxin injection. Intrastriatal administration of 6-OHDA also produced an early and transient augmentation of pan-BDNF, exon II,BDNF, and exon III,BDNF transcripts in the ipsilateral SN. The pan-BDNF and exon II,BDNF transcript increases were completely abolished by the prior systemic administration of MK-801, a selective antagonist of NMDA receptors. MK-801 also blocked the increase in BDNF-IR cells in SN observed 7 days after unilateral 6-OHDA intrastriatal injections. Our findings suggest that a coupling between glutamate release, NMDA receptor activation, and BDNF expression may exist in the adult SN and represent an important signal in this midbrain nucleus triggered in response to partial DA loss occurring in striatal nerve endings during presymptomatic PD. © 2009 Wiley-Liss, Inc. [source] Regional-specific regulation of BDNF and trkB correlates with nigral dopaminergic cell sprouting following unilateral nigrostriatal axotomyJOURNAL OF NEUROSCIENCE RESEARCH, Issue 9 2008J. T. García Navia Abstract Axotomy is a powerful stimulus of axon growth and plastic changes. We investigated the potential role of BDNF/trkB signaling in the sprouting of dopaminergic nigral axons in response to axotomy of the medial forebrain bundle. Tyrosine hydroxylase immunohistochemistry revealed the existence of sprouting mechanisms in the axotomized substantia nigra (SN). Time-course changes of trkB mRNA expression demonstrated a robust increase in an area projecting from the rostral tip of the SN to the glial scar, which coincided with evidence of nigral dopaminergic sprouting. In addition, we found an early loss of this messenger in areas related to the knife cut, which recovered by 7 days postlesion. TrkB down-regulation appeared to be associated to the lesion-induced local damage, as it was restricted to an area showing Fluoro-Jade B, and TUNEL positive cells. In trkB-depleted areas, an inverse correlation between mRNA expressions of BDNF and trkB was apparent. Specific induction of BDNF mRNA was mostly seen in border of areas devoid of trkB mRNA. In contrast, in the areas exhibiting trkB mRNA expression, no BDNF mRNA was detected. We suggest that trkB levels could be a determinant element in regulating BDNF expression. Finally, the search for molecules involved in either promoting or inhibiting axonal growth, demonstrated up-regulation of GAP-43 and Nogo-A mRNA at sites close to the knife transections as early as 1 day postlesion. However, overall, Nogo-A induction was more robust than that seen for GAP-43. © 2008 Wiley-Liss, Inc. [source] | ||||||||||