Key Specifications Table
|Species Reactivity||Key Applications||Host||Format||Antibody Type|
|Ma, R, M||IHC, WB||Sh||Affinity Purified||Polyclonal Antibody|
|Presentation||Purified sheep polyclonal in buffer containing 10 mM HEPES, pH 7.5, 150 mM NaCl, 100 μg/mL BSA and 50% glycerol.|
|Safety Information according to GHS|
|Material Size||100 µL|
Anti-Tyrosine Hydroxylase Antibody SDS
|Anti-Tyrosine Hydroxylase - 2115919||2115919|
|Anti-Tyrosine Hydroxylase - 2136987||2136987|
|Anti-Tyrosine Hydroxylase - 2386487||2386487|
|Anti-Tyrosine Hydroxylase - 2430338||2430338|
|Anti-Tyrosine Hydroxylase - 1970692||1970692|
|Anti-Tyrosine Hydroxylase - 2031806||2031806|
|Anti-Tyrosine Hydroxylase - 2188466||2188466|
|Anti-Tyrosine Hydroxylase - 2324511||2324511|
|Anti-Tyrosine Hydroxylase - 2519288||2519288|
|Reference overview||Application||Species||Pub Med ID|
|Coronin-1 and calcium signaling governs sympathetic final target innervation.|
Suo, D; Park, J; Young, S; Makita, T; Deppmann, CD
The Journal of neuroscience : the official journal of the Society for Neuroscience 35 3893-902 2015
Development of a functional peripheral nervous system requires axons to rapidly innervate and arborize into final target organs and then slow but not halt their growth to establish stable connections while keeping pace with organ growth. Here we examine the role of the NGF-TrkA effector protein, Coronin-1, on postganglionic sympathetic neuron final target innervation. In the absence of Coronin-1 we find that NGF-TrkA-PI3K signaling drives robust axon growth and branching in part by suppressing GSK3β. In contrast, the presence of Coronin-1 (wild-type neurons) suppresses but does not halt NGF-TrkA-dependent growth and branching. This relative suppression in axon growth behaviors is due to Coronin-1-dependent calcium release via PLC-γ1 signaling, which releases PI3K-dependent suppression of GSK3β. Finally, we demonstrate that Coro1a(-/-) mice display sympathetic axon overgrowth and overbranching phenotypes in the developing heart. Together with previous work demonstrating the Coronin-1 expression is NGF dependent, this work suggests that periods before and after NGF-TrkA-induced Coronin-1 expression (and likely other factors) defines two distinct axon growth states, which are critical for proper circuit formation in the sympathetic nervous system.
|Sexual dimorphism in the hypophysiotropic tyrosine hydroxylase-positive neurons in the preoptic area of the teleost, Clarias batrachus.|
Saha, S; Patil, S; Singh, U; Singh, O; Singru, PS
Biology of sex differences 6 23 2015
Dopamine (DA) neurons in the anteroventral periventricular nucleus (AVPV) in the preoptic area (POA) of mammals express estrogen receptors, regulate luteinizing hormone (LH) secretion, and show distinct sexual dimorphism. In teleosts, hypophysiotropic DA neurons of the nucleus preopticus periventricularis (NPP), located in the anteroventral POA, express estrogen receptors, innervate LH cells, and emerged as a neuroanatomical substrate for inhibiting LH cells. Interestingly, the NPP and AVPV seem to share several similarities. Whether DAergic neurons in the NPP show sexual dimorphism is, however, not known. Based on the proposed homology to AVPV and previous studies showing greater tyrosine hydroxylase (TH) mRNA and enzyme activity levels in the brain of female catfish, we hypothesize that females have greater number of DAergic neurons in the NPP and correspondingly more TH-immunoreactive fiber innervation of the pituitary.Adult, male and female Clarias batrachus collected during the prespawning phase of their reproductive cycle were used. Fish were anesthetized and perfused transcardially with phosphate-buffered saline (pH 7.4) and 4 % paraformaldehyde in phosphate buffer. Sections through the rostro-caudal extent of the POA and pituitary were processed for TH immunofluorescence. Using double immunofluorescence, the association between TH-immunoreactive fibers and LH cells in the pituitary was explored. Sections were analyzed using semiquantitative analysis.NPP in POA of C. batrachus has two distinct subdivisions, viz, anterior (NPPa) and posterior (NPPp), and TH neurons were observed in both the subdivisions. Compared to that in the males, a significantly higher (P less than 0.05) number of TH neurons was consistently observed in the NPPa of females. TH neurons in NPPp, however, showed no difference in the number or immunoreactivity. Since DA neurons in NPPa are hypophysiotropic, we compared TH-fiber innervation of the pituitary in both sexes. Compared to males, proximal pars distalis and LH cells in this region of the pituitary in females were densely innervated by TH fibers.Neurons of NPPa and their innervation to the pituitary seem to be a distinct sexually dimorphic DAergic system in C. batrachus. The DAergic system may serve as a component of the neural mechanisms controlling the sexually dimorphic LH surge in teleosts. Given the similarities shared by NPPa and AVPV, homology between these two nuclei is suggested.
|Genome-wide characterisation of Foxa1 binding sites reveals several mechanisms for regulating neuronal differentiation in midbrain dopamine cells.|
Metzakopian, E; Bouhali, K; Alvarez-Saavedra, M; Whitsett, JA; Picketts, DJ; Ang, SL
Development (Cambridge, England) 142 1315-24 2015
Midbrain dopamine neuronal progenitors develop into heterogeneous subgroups of neurons, such as substantia nigra pars compacta, ventral tegmental area and retrorubal field, that regulate motor control, motivated and addictive behaviours. The development of midbrain dopamine neurons has been extensively studied, and these studies indicate that complex cross-regulatory interactions between extrinsic and intrinsic molecules regulate a precise temporal and spatial programme of neurogenesis in midbrain dopamine progenitors. To elucidate direct molecular interactions between multiple regulatory factors during neuronal differentiation in mice, we characterised genome-wide binding sites of the forkhead/winged helix transcription factor Foxa1, which functions redundantly with Foxa2 to regulate the differentiation of mDA neurons. Interestingly, our studies identified a rostral brain floor plate Neurog2 enhancer that requires direct input from Otx2, Foxa1, Foxa2 and an E-box transcription factor for its transcriptional activity. Furthermore, the chromatin remodelling factor Smarca1 was shown to function downstream of Foxa1 and Foxa2 to regulate differentiation from immature to mature midbrain dopaminergic neurons. Our genome-wide Foxa1-bound cis-regulatory sequences from ChIP-Seq and Foxa1/2 candidate target genes from RNA-Seq analyses of embryonic midbrain dopamine cells also provide an excellent resource for probing mechanistic insights into gene regulatory networks involved in the differentiation of midbrain dopamine neurons.
|Dopaminergic and glutamatergic microdomains in a subset of rodent mesoaccumbens axons.|
Zhang, S; Qi, J; Li, X; Wang, HL; Britt, JP; Hoffman, AF; Bonci, A; Lupica, CR; Morales, M
Nature neuroscience 18 386-92 2015
Mesoaccumbens fibers are thought to co-release dopamine and glutamate. However, the mechanism is unclear, and co-release by mesoaccumbens fibers has not been documented. Using electron microcopy, we found that some mesoaccumbens fibers have vesicular transporters for dopamine (VMAT2) in axon segments that are continuous with axon terminals that lack VMAT2, but contain vesicular glutamate transporters type 2 (VGluT2). In vivo overexpression of VMAT2 did not change the segregation of the two vesicular types, suggesting the existence of highly regulated mechanisms for maintaining this segregation. The mesoaccumbens axon terminals containing VGluT2 vesicles make asymmetric synapses, commonly associated with excitatory signaling. Using optogenetics, we found that dopamine and glutamate were released from the same mesoaccumbens fibers. These findings reveal a complex type of signaling by mesoaccumbens fibers in which dopamine and glutamate can be released from the same axons, but are not normally released at the same site or from the same synaptic vesicles.
|Hypothalamic overexpression of mutant huntingtin causes dysregulation of brown adipose tissue.|
Soylu-Kucharz, R; Adlesic, N; Baldo, B; Kirik, D; Petersén, Å
Scientific reports 5 14598 2015
Expression of mutant huntingtin (htt) protein has been shown to cause metabolic imbalance in animal models of Huntington disease (HD). The pathways involved are not fully understood but dysfunction of both the hypothalamus and brown adipose tissue (BAT) has been implicated. Here we show that targeted expression of mutant HTT in the hypothalamus leads to loss of the A13 dopaminergic cell group located in the zona incerta and reduced mRNA expression of neuropeptide Y1 receptor in the hypothalamus. Furthermore, this is accompanied by downregulation of uncoupling protein 1 expression and PPARγ coactivator-1 alpha in BAT and a rapid body weight gain. Taken together, our data might provide a mechanistic link between expression of mutant HTT, reduced activity of a hypothalamic dopaminergic pathway and dysfunction of BAT and in part explain the development of an obese phenotype in HD mouse models.
|Norepinephrine activates dopamine D4 receptors in the rat lateral habenula.|
Root, DH; Hoffman, AF; Good, CH; Zhang, S; Gigante, E; Lupica, CR; Morales, M
The Journal of neuroscience : the official journal of the Society for Neuroscience 35 3460-9 2015
The lateral habenula (LHb) is involved in reward and aversion and is reciprocally connected with dopamine (DA)-containing brain regions, including the ventral tegmental area (VTA). We used a multidisciplinary approach to examine the properties of DA afferents to the LHb in the rat. We find that greater than 90% of VTA tyrosine hydroxylase (TH) neurons projecting to the LHb lack vesicular monoamine transporter 2 (VMAT2) mRNA, and there is little coexpression of TH and VMAT2 protein in this mesohabenular pathway. Consistent with this, electrical stimulation of LHb did not evoke DA-like signals, assessed with fast-scan cyclic voltammetry. However, electrophysiological currents that were inhibited by L741,742, a DA-D4-receptor antagonist, were observed in LHb neurons when DA uptake or degradation was blocked. To prevent DA activation of D4 receptors, we repeated this experiment in LHb slices from DA-depleted rats. However, this did not disrupt D4 receptor activation initiated by the dopamine transporter inhibitor, GBR12935. As the LHb is also targeted by noradrenergic afferents, we examined whether GBR12935 activation of DA-D4 receptors occurred in slices depleted of norepinephrine (NE). Unlike DA, NE depletion prevented the activation of DA-D4 receptors. Moreover, direct application of NE elicited currents in LHb neurons that were blocked by L741,742, and GBR12935 was found to be a more effective blocker of NE uptake than the NE-selective transport inhibitor nisoxetine. These findings demonstrate that NE is released in the rat LHb under basal conditions and that it activates DA-D4 receptors. Therefore, NE may be an important regulator of LHb function.
|Characterization of A11 neurons projecting to the spinal cord of mice.|
Koblinger, K; Füzesi, T; Ejdrygiewicz, J; Krajacic, A; Bains, JS; Whelan, PJ
PloS one 9 e109636 2014
The hypothalamic A11 region has been identified in several species including rats, mice, cats, monkeys, zebrafish, and humans as the primary source of descending dopamine (DA) to the spinal cord. It has been implicated in the control of pain, modulation of the spinal locomotor network, restless leg syndrome, and cataplexy, yet the A11 cell group remains an understudied dopaminergic (DAergic) nucleus within the brain. It is unclear whether A11 neurons in the mouse contain the full complement of enzymes consistent with traditional DA neuronal phenotypes. Given the abundance of mouse genetic models and tools available to interrogate specific neural circuits and behavior, it is critical first to fully understand the phenotype of A11 cells. We provide evidence that, in addition to tyrosine hydroxylase (TH) that synthesizes L-DOPA, neurons within the A11 region of the mouse contain aromatic L-amino acid decarboxylase (AADC), the enzyme that converts L-DOPA to dopamine. Furthermore, we show that the A11 neurons contain vesicular monoamine transporter 2 (VMAT2), which is necessary for packaging DA into vesicles. On the contrary, A11 neurons in the mouse lack the dopamine transporter (DAT). In conclusion, our data suggest that A11 neurons are DAergic. The lack of DAT, and therefore the lack of a DA reuptake mechanism, points to a longer time of action compared to typical DA neurons.
|Pomegranate juice exacerbates oxidative stress and nigrostriatal degeneration in Parkinson's disease.|
Tapias, V; Cannon, JR; Greenamyre, JT
Neurobiology of aging 35 1162-76 2014
Numerous factors contribute to the death of substantia nigra (SN) dopamine (DA) neurons in Parkinson's disease (PD). Compelling evidence implicates mitochondrial deficiency, oxidative stress, and inflammation as important pathogenic factors in PD. Chronic exposure of rats to rotenone causes a PD-like syndrome, in part by causing oxidative damage and inflammation in substantia nigra. Pomegranate juice (PJ) has the greatest composite antioxidant potency index among beverages, and it has been demonstrated to have protective effects in a transgenic model of Alzheimer's disease. The present study was designed to examine the potential neuroprotective effects of PJ in the rotenone model of PD. Oral administration of PJ did not mitigate or prevent experimental PD but instead increased nigrostriatal terminal depletion, DA neuron loss, the inflammatory response, and caspase activation, thereby heightening neurodegeneration. The mechanisms underlying this effect are uncertain, but the finding that PJ per se enhanced nitrotyrosine, inducible nitric oxide synthase, and activated caspase-3 expression in nigral DA neurons is consistent with its potential pro-oxidant activity.
|The anorectic actions of the TGFβ cytokine MIC-1/GDF15 require an intact brainstem area postrema and nucleus of the solitary tract.|
Tsai, VW; Manandhar, R; Jørgensen, SB; Lee-Ng, KK; Zhang, HP; Marquis, CP; Jiang, L; Husaini, Y; Lin, S; Sainsbury, A; Sawchenko, PE; Brown, DA; Breit, SN
PloS one 9 e100370 2014
Macrophage inhibitory cytokine-1 (MIC-1/GDF15) modulates food intake and body weight under physiological and pathological conditions by acting on the hypothalamus and brainstem. When overexpressed in disease, such as in advanced cancer, elevated serum MIC-1/GDF15 levels lead to an anorexia/cachexia syndrome. To gain a better understanding of its actions in the brainstem we studied MIC-1/GDF15 induced neuronal activation identified by induction of Fos protein. Intraperitoneal injection of human MIC-1/GDF15 in mice activated brainstem neurons in the area postrema (AP) and the medial (m) portion of the nucleus of the solitary tract (NTS), which did not stain with tyrosine hydroxylase (TH). To determine the importance of these brainstem nuclei in the anorexigenic effect of MIC-1/GDF15, we ablated the AP alone or the AP and the NTS. The latter combined lesion completely reversed the anorexigenic effects of MIC-1/GDF15. Altogether, this study identified neurons in the AP and/or NTS, as being critical for the regulation of food intake and body weight by MIC-1/GDF15.
|Mesodiencephalic dopaminergic neuronal differentiation does not involve GLI2A-mediated SHH-signaling and is under the direct influence of canonical WNT signaling.|
Mesman, S; von Oerthel, L; Smidt, MP
PloS one 9 e97926 2014
Sonic Hedgehog (SHH) and WNT proteins are key regulators in many developmental processes, like embryonic patterning and brain development. In the brain, SHH is expressed in a gradient starting in the floor plate (FP) progressing ventrally in the midbrain, where it is thought to be involved in the development and specification of mesodiencephalic dopaminergic (mdDA) neurons. GLI2A-mediated SHH-signaling induces the expression of Gli1, which is inhibited when cells start expressing SHH themselves. To determine whether mdDA neurons receive GLI2A-mediated SHH-signaling during differentiation, we used a BAC-transgenic mouse model expressing eGFP under the control of the Gli1 promoter. This mouse-model allowed for mapping of GLI2A-mediated SHH-signaling temporal and spatial in the mouse midbrain. Since mdDA neurons are born from E10.5, peaking at E11.0-E12.0, we examined Gli1-eGFP embryos at E11.5, E12.5, and E13.5, indicating whether Gli1 was induced before or during mdDA development and differentiation. Our data indicate that GLI2A-mediated SHH-signaling is not involved in mdDA neuronal differentiation. However, it appears to be involved in the differentiation of neurons which make up a subset of the red nucleus (RN). In order to detect whether mdDA neuronal differentiation may be under the control of canonical WNT-signaling, we used a transgenic mouse-line expressing LacZ under the influence of stable β-catenin. Here, we show that TH+ neurons of the midbrain receive canonical WNT-signaling during differentiation. Therefore, we suggest that early SHH-signaling is indirectly involved in mdDA development through early patterning of the midbrain area, whereas canonical WNT-signaling is directly involved in the differentiation of the mdDA neuronal population.