Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.14.16.2 (tyrosine hydroxylase)
 14,760 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The lateral habenular complex is part of the habenular nuclei, a distinct structure in the dorsal diencephalon of all vertebrates. In contrast to the bewildering diversity of behaviors, in which the lateral habenular complex is thought to be involved, there is an astonishing lack of information concerning its cellular organization, its neuronal circuits, and the neurophysiological mechanisms, which may provide the physiological and molecular basis for its diverse biological functions. This problem may be due to an unexpected heterogeneity of the lateral habenular complex. Recently, a detailed subnuclear organization has been described (Andres et al. [1999] J Comp Neurol 407:130-150), which provides the base for a subsequent physiological and behavioral analysis of this area. Available criteria, however, can be applied to semithin sections only. To facilitate further investigations, the present work aimed to elaborate novel morphologic and immunocytochemical criteria that can be applied to conventional cryostat or Vibratome sections to allow identification and delineation of subnuclei of the lateral habenular complex. Consequently, the regional, cellular, and subcellular localization of approximately 30 different neuroactive molecules was investigated. Of these candidate molecules, gamma-aminobutyric acid-B receptor protein, Kir3.2 potassium channel protein, tyrosine hydroxylase, and neurofilament heavy chain proved to be suitable markers. Our observation suggests that the habenular subnuclei express distinct immunocytochemical characteristics. These features may be used to identify and delineate the subnuclei on conventional cryostat or Vibratome sections. From our results, it is expected that the further functional analysis of the lateral habenular complex will be facilitated considerably.
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PMID:Morphologic and cytochemical criteria for the identification and delineation of individual subnuclei within the lateral habenular complex of the rat. 1257 24

1. Dopaminergic neurons in the substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA) of the ventral mesencephalon play an important role in the regulation of the parallel basal ganglia loops.2. We have raised affinity-purified polyclonal rabbit antibodies specific for all four members of the Kir3 family of inwardly rectifying potassium channels (Kir3.1-Kir3.4) to investigate the distribution of the channel proteins in the dopaminergic neurons of the rat mesencephalon at light and electron microscopic level. In addition, immunocytochemical double labeling with tyrosine hydroxylase (TH), a marker of dopaminergic neurons, were performed.3. All Kir3 channels were present in this region. However, the individual proteins showed differential cellular and subcellular distributions.4. Kir3.1 immunoreactivity was found in SNc fibers and some neurons of the substantia nigra pars reticulata (SNr). Few Kir3.3-positive neurons were found in the SNc. However, a strong Kir3.3 signal was identified in the SNr neuropil. Weak Kir3.4 staining was detected in neuronal somata as well as in dendritic fibers of both parts of the SN.5. In the VTA, Kir3.1, Kir3.3, and Kir3.4 showed only weak staining of neuropil structures. The distribution of the Kir3.2 channel protein was especially striking with strong labeling in the SNc and in the lateral but not central VTA.6. Our results suggest that the heterogeneously distributed Kir3.2 channel proteins could help to discriminate the dopaminergic neurons of VTA and SNc.
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PMID:Heterogeneous distribution of kir3 potassium channel proteins within dopaminergic neurons in the mesencephalon of the rat brain. 1723 95

Human induced pluripotent stem cells (hiPSCs) offer the potential to study otherwise inaccessible cell types. Critical to this is the directed differentiation of hiPSCs into functional cell lineages. This is of particular relevance to research into neurological disease, such as Parkinson's disease (PD), in which midbrain dopaminergic neurons degenerate during disease progression but are unobtainable until post-mortem. Here we report a detailed study into the physiological maturation over time of human dopaminergic neurons in vitro. We first generated and differentiated hiPSC lines into midbrain dopaminergic neurons and performed a comprehensive characterisation to confirm dopaminergic functionality by demonstrating dopamine synthesis, release, and re-uptake. The neuronal cultures include cells positive for both tyrosine hydroxylase (TH) and G protein-activated inward rectifier potassium channel 2 (Kir3.2, henceforth referred to as GIRK2), representative of the A9 population of substantia nigra pars compacta (SNc) neurons vulnerable in PD. We observed for the first time the maturation of the slow autonomous pace-making (<10 Hz) and spontaneous synaptic activity typical of mature SNc dopaminergic neurons using a combination of calcium imaging and electrophysiology. hiPSC-derived neurons exhibited inositol tri-phosphate (IP3) receptor-dependent release of intracellular calcium from the endoplasmic reticulum in neuronal processes as calcium waves propagating from apical and distal dendrites, and in the soma. Finally, neurons were susceptible to the dopamine neuron-specific toxin 1-methyl-4-phenylpyridinium (MPP+) which reduced mitochondrial membrane potential and altered mitochondrial morphology. Mature hiPSC-derived dopaminergic neurons provide a neurophysiologically-defined model of previously inaccessible vulnerable SNc dopaminergic neurons to bridge the gap between clinical PD and animal models.
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PMID:Physiological characterisation of human iPS-derived dopaminergic neurons. 2458 73