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)

Prenatal exposure to chemicals is well known to induce developmental abnormalities in the central nervous system of children. Developmental neurotoxicity (DNT) tests are important to identify neurotoxic agents and prevent neurodevelopmental disorders. We have investigated DNT, focusing on the fetal brain shortly after chemical exposure. To demonstrate a usefulness of a study focusing on the fetal brain in DNT tests, we assessed the fetal brain in a rat valproate-induced autism model. Rats were treated with sodium valproate (VPA, 800 mg/kg) orally on gestational day (GD) 9 or 11 (VPA9 or VPA11), and the fetal brains were examined on GD16 using immunohistochemistry for serotonin (5-HT), tyrosine hydroxylase (TH), and TuJ1 (neuron specific class III beta-tubulin). Hypoplasia of the cortical plate was induced in both VPA9 and VPA11 groups. Abnormal migration of TH-positive and 5-HT neurons, possibly due to the appearance of an abnormally running nerve tract in the pons, was observed only in the VPA11 group. In addition, when we compared the incidence of these abnormalities between pregnant rats mated in our own animal facility (in-house group), and rats purchased pregnant (supplier group), the supplier group was much more sensitive, especially to the pons abnormality. Shipping stress may affect the reproducibility of VPA-induced DNT. The present results demonstrate that examination of the GD16 fetal brain was useful for detecting and characterizing abnormal development of the brain after VPA exposure. Further discussion was made with reference to the findings in children with autism.
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PMID:Observation of fetal brain in a rat valproate-induced autism model: a developmental neurotoxicity study. 1946 Jun 35

Neuronal progenitor cells (NPCs) possess high potential for use in regenerative medicine. To overcome their limited mitotic competence, various immortalization strategies have been applied that allow their prolonged maintenance and expansion in vitro. Such immortalized cells can be used for the design and discovery of new cell-based therapies for neurodegenerative diseases, such as Parkinson's disease. We immortalized rat ventral mesencephalic NPCs by using SV40 large T antigen (SV40Tag). All cell clones displayed a two- to three-fold higher proliferation rate compared with the primary cells. In order to induce dopaminergic differentiation of generated cell clones, both glial-derived neurotrophic factor and di-butyryl cyclic adenosine monophosphate were applied. Treated cells were then characterized regarding the expression of dopaminergic lineage markers, differentiation of various cell populations, calcium imaging in the presence of kainate, and immunohistochemistry after intrastriatal transplantation. Treated cells displayed morphological maturation, and calcium imaging revealed neuronal properties in the presence of kainate. These cells also expressed low mRNA levels of the dopamine transporter and tyrosine hydroxylase (TH), although no TH-immunopositive neurons were found. Intrastriatal transplantation into the neurotoxin-lesioned rats did not induce further differentiation. As an alternative approach, we silenced SV40Tag with short interfering RNA, but this was not sufficient to trigger differentiation into dopaminergic neurons. Nevertheless, neuronal and glial cells were detected as shown by beta-tubulin type III and glial fibrillary acidic protein staining, respectively. SV40Tag cells are suitable for carrying out controlled genetic modifications as shown by overexpression of enhanced green fluorescence protein after efficient non-viral transfection.
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PMID:Characterization and differentiation potential of rat ventral mesencephalic neuronal progenitor cells immortalized with SV40 large T antigen. 2017 6

After peripheral nerve injury, regeneration or collateral sprouting of noradrenergic nerve fibres in the papillary dermis of the injured limb may contribute to sympathetically-maintained pain. The aim of this study was to determine whether noradrenergic nerve fibre regeneration after partial sciatic nerve ligation (PSL) in Wistar rats was accompanied by parallel shifts in expression of the noradrenaline transporter (NAT). Four or 28 days after PSL surgery, immunohistochemistry was used to examine NAT expression in plantar hind paw skin in relation to pan-neuronal markers (class III beta-tubulin and protein gene product 9.5), peptidergic afferents containing calcitonin gene-related peptide (CGRP), nonpeptidergic afferents labelled by isolectin B4 (IB4), and tyrosine hydroxylase (TH), a marker for cutaneous noradrenergic nerve fibres. Most dermal nerve fibre populations decreased shortly after PSL. However, four weeks after PSL, an increase in staining intensity of CGRP and novel expression of TH were observed in the papillary dermis on the injured side. In contrast, neural expression of NAT was reduced in this region. Loss of NAT might have implications for sympathetically-maintained pain, as failure to rapidly clear noradrenaline could exacerbate aberrant sympathetic-sensory signalling between closely apposed noradrenergic and peptidergic nerve fibres.
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PMID:Decreased neural expression of the noradrenaline transporter in the papillary dermis after partial sciatic nerve lesion. 3247 20


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