Key Specifications Table
|Species Reactivity||Key Applications||Host||Format||Antibody Type|
|Ch, H, R||ELISA, IHC, FUNC, WB||Sh||Purified||Polyclonal Antibody|
|Description||Anti-Brain Derived Neurotrophic Factor Antibody|
|Presentation||Protein G Purified immunoglobulin. Lyophilized from PBS, no preservatives. Reconstitute with 500 μL of sterile distilled water.|
|Safety Information according to GHS|
|Material Size||500 µg|
References | 16 Available | See All References
|Reference overview||Pub Med ID|
|Hippocampal--prefrontal BDNF and memory for fear extinction. |
Rosas-Vidal, LE; Do-Monte, FH; Sotres-Bayon, F; Quirk, GJ
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 39 2161-9 2014
Infusing brain-derived neurotrophic factor (BDNF) into the infralimbic (IL) prefrontal cortex is capable of inducing extinction. Little is known, however, about the circuits mediating BDNF effects on extinction or the extent to which extinction requires BDNF in IL. Using local pharmacological infusion of BDNF protein, or an antibody against BDNF, we found that BDNF in the IL, but not prelimbic (PL) prefrontal cortex, is both necessary and sufficient for fear extinction. Furthermore, we report that BDNF in IL can induce extinction of older fear memories (14 days) as well as recent fear memories (1 day). Using immunocytochemistry, we show that BDNF is increased in the ventral hippocampus (vHPC), but not IL or PL, following extinction training. Finally, we observed that infusing BDNF into the vHPC increased the firing rate of IL, but not PL neurons in fear conditioned rats. These findings indicate that an extinction-induced increase in BDNF within the vHPC enhances excitability in IL targets, thereby supporting extinction memories.
|Sexual differences in cell proliferation in the ventricular zone, cell migration and differentiation in the HVC of juvenile Bengalese finch. |
Chen, Q; Zhang, X; Zhao, Y; Zhou, X; Sun, L; Zeng, S; Zuo, M; Zhang, X
PloS one 9 e97403 2014
Song control nuclei have distinct sexual differences and thus are an ideal model to address how brain areas are sexually differentiated. Through a combination of histological analysis and electrical lesions, we first identified the ventricle site for HVC progenitor cells. We then found that there were significant sex differences in the cellular proliferation activity in the ventricular zone of the HVC, the number of migrating cells along the radial cells (positive immunoreactions to vimentin) and differentiation towards neurons. Through co-culturing of male and female slices containing the developing HVC in the same well, we found that the male slices could produce diffusible substances to masculinize the female HVC. By adding estrogen, an estrogen antagonist, brain-derived neurotrophic factor (BDNF) or its antibody into the culture medium, separately or in combination, we found that these diffusible substances may include estrogen and BDNF. Finally, we found that 1) estrogen-induced BDNF upregulation could be detected 48 hr after estrogen treatment and could not be blocked by a vascular endothelial growth factor (VEGF) receptor inhibitor and 2) the amount of VEGF mRNA expressed in the developing HVC and its adjacent area did not display any significant sex differences, as did the distribution of VEGF and laminin-expressing endothelial cells in the developing HVC. Because these findings are largely different from previous reports on the adult female HVC, it is suggested that our estrogen-induced BDNF up-regulation and the resultant sexual differentiation might not be mediated by VEGF and endothelial cells, but instead, may result from the direct effects of estrogen on BDNF.
|Feedback mechanism in depolarization-induced sustained activation of extracellular signal-regulated kinase in the hippocampus. |
Maharana, C; Sharma, KP; Sharma, SK
Scientific reports 3 1103 2013
Phosphorylation plays important roles in several processes including synaptic plasticity and memory. The critical role of extracellular signal-regulated kinase (ERK) in these processes is well established. ERK is activated in a sustained manner by different stimuli. However, the mechanisms of sustained ERK activation are not completely understood. Here we show that KCl depolarization-induced sustained ERK activation in the hippocampal slices is critically dependent on protein synthesis and transcription. In addition, the sustained ERK activation requires receptor tyrosine kinase(s) activity. In support of a role for a growth factor in sustained ERK activation, KCl depolarization enhances the level of brain-derived neurotrophic factor (BDNF). Furthermore, BDNF antibody blocks KCl-induced sustained ERK activation. These results suggest a positive feed-back loop in which depolarization-induced BDNF maintains ERK activation in the sustained phase.
|Motoneuron programmed cell death in response to proBDNF. |
Taylor, AR; Gifondorwa, DJ; Robinson, MB; Strupe, JL; Prevette, D; Johnson, JE; Hempstead, B; Oppenheim, RW; Milligan, CE
Developmental neurobiology 72 699-712 2012
Motoneurons (MN) as well as most neuronal populations undergo a temporally and spatially specific period of programmed cell death (PCD). Several factors have been considered to regulate the survival of MNs during this period, including availability of muscle-derived trophic support and activity. The possibility that target-derived factors may also negatively regulate MN survival has been considered, but not pursued. Neurotrophin precursors, through their interaction with p75(NTR) and sortilin receptors have been shown to induce cell death during development and following injury in the CNS. In this study, we find that muscle cells produce and secrete proBDNF. ProBDNF through its interaction with p75(NTR) and sortilin, promotes a caspase-dependent death of MNs in culture. We also provide data to suggest that proBDNF regulates MN PCD during development in vivo.
|Smilagenin attenuates beta amyloid (25-35)-induced degeneration of neuronal cells via stimulating the gene expression of brain-derived neurotrophic factor. |
R Zhang,Z Wang,P A Howson,Z Xia,S Zhou,E Wu,Y Hu
Neuroscience 210 2012
The development of drugs that attenuate neurodegeneration is important for the treatment of Alzheimer's disease (AD). We previously found that smilagenin (SMI), a steroidal sapogenin from traditional Chinese medicinal herbs improves memory in animal models, is neither a cholinesterase inhibitor nor a glutamate receptor antagonist, but can significantly elevate the declined muscarinic receptor (M receptor) density. In this article, to clarify whether SMI represents a new approach for treating neurodegeneration disease, we first demonstrate that SMI pretreatment significantly attenuates the neurodegenerative changes induced by beta amyloid 25-35 (Aβ(25-35)) in cultured rat cortical neurons, including decreased cholinergic neuron number, shortened neurite outgrowth length, and declined M receptor density. Brain-derived neurotrophic factor (BDNF) protein levels in the culture medium were also decreased by Aβ(25-35) and significantly elevated by SMI. Parallel experiments revealed that when the trk receptors were inhibited by K252a or the action of BDNF was inhibited by a neutralizing anti-BDNF antibody, the effects of SMI on the Aβ(25-35)-induced neurodegeneration in rat cortical neurons were almost completely abolished. In the all-trans retinoic acid (RA)-differentiated SH-SY5Y neuroblastoma cells, the BDNF transcription rate measured by a nuclear run-on assay was significantly suppressed by Aβ(25-35) and elevated by SMI, but the BDNF degradation rate measured by half-life determination was unchanged by Aβ(25-35) and SMI. Transcript analysis of the SH-SY5Y cells using quantitative RT-PCR (qRT-PCR) showed that the IV and VI transcripts of BDNF mRNA were significantly decreased by Aβ(25-35) and elevated by SMI. Taken together, we conclude that SMI attenuates Aβ(25-35)-induced neurodegeneration in cultured rat cortical neurons and SH-SY5Y cells mainly through stimulating BDNF mRNA transcription implicating that SMI may represent a novel therapeutic strategy for AD.
|Trk activation of the ERK1/2 kinase pathway stimulates intermediate chain phosphorylation and recruits cytoplasmic dynein to signaling endosomes for retrograde axonal transport. |
Mitchell, DJ; Blasier, KR; Jeffery, ED; Ross, MW; Pullikuth, AK; Suo, D; Park, J; Smiley, WR; Lo, KW; Shabanowitz, J; Deppmann, CD; Trinidad, JC; Hunt, DF; Catling, AD; Pfister, KK
The Journal of neuroscience : the official journal of the Society for Neuroscience 32 15495-510 2012
The retrograde transport of Trk-containing endosomes from the axon to the cell body by cytoplasmic dynein is necessary for axonal and neuronal survival. We investigated the recruitment of dynein to signaling endosomes in rat embryonic neurons and PC12 cells. We identified a novel phosphoserine on the dynein intermediate chains (ICs), and we observed a time-dependent neurotrophin-stimulated increase in intermediate chain phosphorylation on this site in both cell types. Pharmacological studies, overexpression of constitutively active MAP kinase kinase, and an in vitro assay with recombinant proteins demonstrated that the intermediate chains are phosphorylated by the MAP kinase ERK1/2, extracellular signal-regulated kinase, a major downstream effector of Trk. Live cell imaging with fluorescently tagged IC mutants demonstrated that the dephosphomimic mutants had significantly reduced colocalization with Trk and Rab7, but not a mitochondrial marker. The phosphorylated intermediate chains were enriched on immunoaffinity-purified Trk-containing organelles. Inhibition of ERK reduced the amount of phospho-IC and the total amount of dynein that copurified with the signaling endosomes. In addition, inhibition of ERK1/2 reduced the motility of Rab7- and TrkB-containing endosomes and the extent of their colocalization with dynein in axons. NGF-dependent survival of sympathetic neurons was significantly reduced by the overexpression of the dephosphomimic mutant IC-1B-S80A, but not WT IC-1B, further demonstrating the functional significance of phosphorylation on this site. These results demonstrate that neurotrophin binding to Trk initiates the recruitment of cytoplasmic dynein to signaling endosomes through ERK1/2 phosphorylation of intermediate chains for their subsequent retrograde transport in axons.
|Upregulation of CREB-mediated transcription enhances both short- and long-term memory. |
Suzuki, A; Fukushima, H; Mukawa, T; Toyoda, H; Wu, LJ; Zhao, MG; Xu, H; Shang, Y; Endoh, K; Iwamoto, T; Mamiya, N; Okano, E; Hasegawa, S; Mercaldo, V; Zhang, Y; Maeda, R; Ohta, M; Josselyn, SA; Zhuo, M; Kida, S
The Journal of neuroscience : the official journal of the Society for Neuroscience 31 8786-802 2011
Unraveling the mechanisms by which the molecular manipulation of genes of interest enhances cognitive function is important to establish genetic therapies for cognitive disorders. Although CREB is thought to positively regulate formation of long-term memory (LTM), gain-of-function effects of CREB remain poorly understood, especially at the behavioral level. To address this, we generated four lines of transgenic mice expressing dominant active CREB mutants (CREB-Y134F or CREB-DIEDML) in the forebrain that exhibited moderate upregulation of CREB activity. These transgenic lines improved not only LTM but also long-lasting long-term potentiation in the CA1 area in the hippocampus. However, we also observed enhanced short-term memory (STM) in contextual fear-conditioning and social recognition tasks. Enhanced LTM and STM could be dissociated behaviorally in these four lines of transgenic mice, suggesting that the underlying mechanism for enhanced STM and LTM are distinct. LTM enhancement seems to be attributable to the improvement of memory consolidation by the upregulation of CREB transcriptional activity, whereas higher basal levels of BDNF, a CREB target gene, predicted enhanced shorter-term memory. The importance of BDNF in STM was verified by microinfusing BDNF or BDNF inhibitors into the hippocampus of wild-type or transgenic mice. Additionally, increasing BDNF further enhanced LTM in one of the lines of transgenic mice that displayed a normal BDNF level but enhanced LTM, suggesting that upregulation of BDNF and CREB activity cooperatively enhances LTM formation. Our findings suggest that CREB positively regulates memory consolidation and affects memory performance by regulating BDNF expression.
|Endogenous BDNF regulates induction of intrinsic neuronal growth programs in injured sensory neurons. |
Nicole M Geremia,Lina M E Pettersson,J C Hasmatali,Todd Hryciw,Nils Danielsen,David J Schreyer,Valerie M K Verge
Experimental neurology 223 2010
Identification of the molecule(s) that globally induce a robust regenerative state in sensory neurons following peripheral nerve injury remains elusive. A potential candidate is brain-derived neurotrophic factor (BDNF), the sole neurotrophin upregulated in sensory neurons after peripheral nerve injury. Here we tested the hypothesis that BDNF plays a critical role in the regenerative response of mature rat sensory neurons following peripheral nerve lesion. Neutralization of endogenous BDNF was performed by infusing BDNF antibodies intrathecally via a mini-osmotic pump for 3 days at the level of the fifth lumbar dorsal root ganglion, immediately following unilateral spinal nerve injury. This resulted in decreased expression of the injury/regeneration-associated genes growth-associated protein-43 and Talpha1 tubulin in the injured sensory neurons as compared to injury plus control IgG infused or injury alone animals. Similar results were observed following inhibition of BDNF expression by intrathecal delivery of small interfering RNAs (siRNA) targeting BDNF starting 3 days prior to injury. The reduced injury/regeneration-associated gene expression correlated with a significantly reduced intrinsic capacity of these neurons to extend neurites when assayed in vitro. In contrast, delayed infusion of BDNF antibody for 3 days beginning 1 week post-lesion had no discernible influence on the elevated expression of these regeneration-associated markers. These results support an important role for endogenous BDNF in induction of the cell body response in injured sensory neurons and their intrinsic ability to extend neurites, but BDNF does not appear to be necessary for maintaining the response once it is induced.
|PSA-NCAM-dependent GDNF signaling limits neurodegeneration and epileptogenesis in temporal lobe epilepsy. |
Venceslas Duveau,Jean-Marc Fritschy
The European journal of neuroscience 32 2010
Polysialylated neuronal cell adhesion molecule (PSA-NCAM), a polysialylated protein constitutively expressed in the hippocampus, is involved in neuronal growth, synaptic plasticity and neurotrophin signaling. In particular, PSA-NCAM mediates Ret-independent glial-derived neurotrophic factor (GDNF) signaling, leading to downstream FAK activation. GDNF has potent seizure-suppressant action, whereas PSA-NCAM is upregulated by seizure activity. However, the involvement of Ret-independent GDNF signaling in temporal lobe epilepsy (TLE) is not established. We tested the effects of PSA-NCAM inactivation on neurodegeneration and epileptogenesis in a mouse model of TLE. In this model, unilateral intrahippocampal kainic acid (KA) injection induced degeneration of CA1, CA3c and hilar neurons, followed by spontaneous recurrent focal seizures. In the contralateral, morphologically preserved hippocampus, a long-lasting increase of PSA-NCAM immunoreactivity was observed. Inactivation of PSA-NCAM by endoneuraminidase (EndoN) administration into the contralateral ventricle of KA-treated mice caused severe degeneration of CA3a,b neurons and dentate gyrus granule cells in the epileptic focus, and led to early onset of focal seizures. This striking trans-hemispheric alteration suggested that PSA-NCAM mediates GDNF signaling, leading to transport of neuroprotective signals into the lesioned hippocampus. This hypothesis was confirmed by injecting GDNF antibodies into the contralateral hippocampus of KA-treated mice, thereby reproducing the enhanced neurodegeneration seen after PSA-NCAM inactivation. Furthermore, contralateral EndoN and anti-GDNF treatment decreased GDNF family receptor alpha1 immunoreactivity and FAK phosphorylation in the epileptic focus. Thus, Ret-independent GDNF signaling across the commissural projection might protect CA3a,b neurons and delay seizure onset. These findings implicate GDNF in the control of epileptogenesis and offer a possible mechanism explaining lesion asymmetry in mesial TLE.
|Spinal alpha 2-adrenoceptor-mediated analgesia in neuropathic pain reflects brain-derived nerve growth factor and changes in spinal cholinergic neuronal function. |
Ken-ichiro Hayashida,James C Eisenach
Anesthesiology 113 2010
Spinal alpha2-adrenoceptor stimulation produces analgesia in neuropathic pain states, and this effect in animals is blocked by the inhibitors of brain-derived neurotrophic factor (BDNF) function. In rats, alpha2-adrenoceptor stimulation normally inhibits acetylcholine release, but it excites release after nerve injury. The authors examined the roles of BDNF and excitatory Gs-protein in this change.Full Text Article
|BDNF activates mTOR to regulate GluR1 expression required for memory formation. |
Slipczuk, L; Bekinschtein, P; Katche, C; Cammarota, M; Izquierdo, I; Medina, JH
PloS one 4 e6007 2009
The mammalian target of Rapamycin (mTOR) kinase plays a key role in translational control of a subset of mRNAs through regulation of its initiation step. In neurons, mTOR is present at the synaptic region, where it modulates the activity-dependent expression of locally-translated proteins independently of mRNA synthesis. Indeed, mTOR is necessary for different forms of synaptic plasticity and long-term memory (LTM) formation. However, little is known about the time course of mTOR activation and the extracellular signals governing this process or the identity of the proteins whose translation is regulated by this kinase, during mnemonic processing.Here we show that consolidation of inhibitory avoidance (IA) LTM entails mTOR activation in the dorsal hippocampus at the moment of and 3 h after training and is associated with a rapid and rapamycin-sensitive increase in AMPA receptor GluR1 subunit expression, which was also blocked by intra-hippocampal delivery of GluR1 antisense oligonucleotides (ASO). In addition, we found that pre- or post-training administration of function-blocking anti-BDNF antibodies into dorsal CA1 hampered IA LTM retention, abolished the learning-induced biphasic activation of mTOR and its readout, p70S6K and blocked GluR1 expression, indicating that BDNF is an upstream factor controlling mTOR signaling during fear-memory consolidation. Interestingly, BDNF ASO hindered LTM retention only when given into dorsal CA1 1 h after but not 2 h before training, suggesting that BDNF controls the biphasic requirement of mTOR during LTM consolidation through different mechanisms: an early one involving BDNF already available at the moment of training, and a late one, happening around 3 h post-training that needs de novo synthesis of this neurotrophin.IN CONCLUSION, OUR FINDINGS DEMONSTRATE THAT: 1) mTOR-mediated mRNA translation is required for memory consolidation during at least two restricted time windows; 2) this kinase acts downstream BDNF in the hippocampus and; 3) it controls the increase of synaptic GluR1 necessary for memory consolidation.
|Brain-derived neurotrophic factor (BDNF)-like immunoreactivity localization in the retina and brain of Cichlasoma dimerus (Teleostei, Perciformes). |
P G Vissio, M M Cánepa, M C Maggese, P G Vissio, M M Cánepa, M C Maggese
Tissue cell 40 261-70 2008
Brain-derived neurotrophic factor (BDNF) is a neurotrophin involved in the development and maintenance of vertebrate nervous systems. Although there were several studies in classical animal models, scarce information for fish was available. The main purpose of this study was to analyze the distribution of BDNF in the brain and retina of the cichlid fish Cichlasoma dimerus. By immunohistochemistry we detected BDNF-like immunoreactive cells in the cytoplasm and the nuclei of the ganglion cell layer and the inner nuclear layer of the retina. In the optic tectum, BDNF-like immunoreactivity was detected in the nucleus of neurons of the stratum periventriculare and the stratum marginale and in neurons of the intermediate layers. In the hypothalamus we found BDNF-like immunoreactivity mainly in the cytoplasm of the nucleus lateralis tuberis and the nucleus of the lateral recess. To confirm the nuclear and cytoplasm localization of BDNF we performed subcellular fractionation, followed by Western blot, detecting a 39 kDa immunoreactive-band corresponding to a possible precursor form of BDNF in both fractions. BDNF-like immunoreactivity was distributed in areas related with photoreception (retina), the integration center of retinal projections (optic tectum) and the control center of background and stress adaptation (hypothalamus). These results provide baseline anatomical information for future research about the role of neurotrophins in the adult fish central nervous system.
|Astrocyte and muscle-derived secreted factors differentially regulate motoneuron survival. |
Taylor, AR; Gifondorwa, DJ; Newbern, JM; Robinson, MB; Strupe, JL; Prevette, D; Oppenheim, RW; Milligan, CE
The Journal of neuroscience : the official journal of the Society for Neuroscience 27 634-44 2007
During development, motoneurons (MNs) undergo a highly stereotyped, temporally and spatially defined period of programmed cell death (PCD), the result of which is the loss of 40-50% of the original neuronal population. Those MNs that survive are thought to reflect the successful acquisition of limiting amounts of trophic factors from the target. In contrast, maturation of MNs limits the need for target-derived trophic factors, because axotomy of these neurons in adulthood results in minimal neuronal loss. It is unclear whether MNs lose their need for trophic factors altogether or whether, instead, they come to rely on other cell types for nourishment. Astrocytes are known to supply trophic factors to a variety of neuronal populations and thus may nourish MNs in the absence of target-derived factors. We investigated the survival-promoting activities of muscle- and astrocyte-derived secreted factors and found that astrocyte-conditioned media (ACM) was able to save substantially more motoneurons in vitro than muscle-conditioned media (MCM). Our results indicate that both ACM and MCM are significant sources of MN trophic support in vitro and in ovo, but only ACM can rescue MNs after unilateral limb bud removal. Furthermore, we provide evidence suggesting that MCM facilitates the death of a subpopulation of MNs in a p75(NTR) - and caspase-dependent manner; however, maturation in ACM results in MN trophic independence and reduced vulnerability to this negative, pro-apoptotic influence from the target.
|Brain-derived neurotrophic factor augments peristalsis by augmenting 5-HT and calcitonin gene-related peptide release. |
Grider John R JR, Piland Barbara E BE, Gulick Melisa A MA, Qiao Li Ya LY
Gastroenterology 130 771-80 2006
BACKGROUND AIMS: Brain-derived neurotrophic factor (BDNF) acts rapidly to modulate synaptic neurotransmission in the brain. Although present in neurons, glial cells, and mucosal cells of the colon, and in higher concentrations than in brain, the action of BDNF in gut have not been characterized. The aim of this study was to identify the role of BDNF in mediating the peristaltic reflex. METHODS: BDNF and a specific antiserum were examined for their effects on the peristaltic reflex and release of the sensory mediators serotonin and calcitonin gene-related peptide in rat colon. The peristaltic reflex and release of serotonin and calcitonin gene-related peptide were also examined in genetically modified mice (BDNF(+/-)) with reduced levels of BDNF. RESULTS: Endogenous brain-derived neurotrophic factor was released into the sensory compartment in a stimulus-dependent manner during the peristaltic reflex induced by mucosal stimulation but not muscle stretch. BDNF stimulated and immunoneutralization of endogenous BDNF reduced ascending contraction and descending relaxation of circular muscle and release of serotonin and calcitonin gene-related peptide during the peristaltic reflex induced by mucosal stimulation but not muscle stretch. The peristaltic reflex and release of serotonin and calcitonin gene-related peptide during the peristaltic reflex induced by mucosal stimulation but not muscle stretch were significantly reduced in BDNF(+/-) mice. CONCLUSIONS: Endogenous BDNF enhances the peristaltic reflex by augmenting the release of serotonin and calcitonin gene-related peptide that mediate the sensory limb of the reflex induced by mucosal stimulation.
|ONO-5046 attenuation of delayed motor neuron death and effect on the induction of brain-derived neurotrophic factor, phosphorylated extracellular signal-regulated kinase, and caspase3 after spinal cord ischemia in rabbits. |
Takashi Yamauchi, Yoshiki Sawa, Masahiro Sakurai, Takano Hiroshi, Goro Matsumiya, Koji Abe, Hikaru Matsuda
The Journal of thoracic and cardiovascular surgery 131 644-50 2006
OBJECTIVE: The mechanism of spinal cord injury is believed to be related to the vulnerability of spinal motor neuron cells to ischemia. The aim of this study was to investigate whether ONO-5046, a specific inhibitor of neutrophil elastase that can attenuate tissue or organ injury in various pathologic conditions, could protect against ischemic spinal cord damage. METHODS: After induction of spinal ischemia, ONO-5046 or vehicle was injected intravenously. Cell damage was analyzed by counting the number of motor neurons. To investigate the mechanism by which ONO-5046 prevents ischemic spinal cord damage, we observed the immunoreactivity of CPP32 (caspase3), brain-derived neurotrophic factor, and phosphorylated extracellular signal-regulated kinase. RESULTS: ONO-5046 eased the functional deficits and increased the number of motor neurons after ischemia. The induction of caspase3 was significantly reduced by ONO-5046 treatment. Furthermore, the expressions of brain-derived neurotrophic factor and phosphorylated extracellular signal-regulated kinase were prolonged. CONCLUSION: ONO-5046 may protect motor neurons from ischemic injury by reducing caspase3 and prolonging the expressions of brain-derived neurotrophic factor and phosphorylated extracellular signal-regulated kinase. ONO-5046 may be a strong candidate for use as a therapeutic agent in the treatment of ischemic spinal cord injury.
|Neutralization of neutrophin-3 in the ventral tegmental area or nucleus accumbens differentially modulates cocaine-induced behavioral plasticity in rats. |
Antoinette Y Freeman, R Christopher Pierce, Antoinette Y Freeman, R Christopher Pierce
Synapse (New York, N.Y.) 46 57-65 2002
These experiments were designed to assess the influence of neurotrophin-3 (NT-3) and brain-derived neurotrophic factor (BDNF) in the mesoaccumbens dopamine system on the initiation of behavioral sensitization to cocaine. A neutralizing antibody for NT-3, BDNF or their vehicle was administered into the ventral tegmental area (VTA) or nucleus accumbens prior to each of four daily injections of 15 mg/kg cocaine. Behavioral sensitization was operationally defined as a significant increase in the behavioral response to cocaine relative to the first daily injection. Results indicated that the NT-3 antibody had differential effects when administered into the VTA or nucleus accumbens. Intra-VTA microinjection of anti-NT-3 resulted in enhanced sensitization to repeated cocaine injections in that the cocaine-induced behavioral response in the anti-NT-3 group was significantly greater than the vehicle group following the second and third daily injections of cocaine. Administration of anti-NT-3 into the nucleus accumbens increased the behavioral response to cocaine over all 4 days of cocaine administration, with no sensitization of this behavioral response. In contrast, pretreatment with anti-BDNF into the VTA or nucleus accumbens had no influence on the initiation of behavioral sensitization to cocaine. Taken together, these data indicate that neutralization of NT-3 in the VTA enhances cocaine-induced behavioral sensitization, while administration of the NT-3 antibody into the nucleus accumbens increases the hyperactive behavioral response induced by cocaine but impairs the further development of behavioral sensitization.
|An Introduction to Antibodies and Their Applications|
|SHEEP ANTI-BRAIN DERIVED NEUROTROPHIC FACTOR (IgG Fraction) POLYCLONAL ANTIBODY|