title: Neuronal tryptophan hydroxylase expression in BALB/cJ and C57Bl/6J mice.
abstract: BALB/c is an inbred stress-sensitive mouse strain exhibiting low brain serotonin (5-HT) content and a 5-HT biosynthetic enzyme tryptophan hydroxylase (Tph2) variant reported to have lower catalytic activity compared with other inbred base strains. To evaluate other mechanisms that may explain low 5-HT, we compared BALB/cJ mice and a control inbred strain C57Bl/6J mice, for expression of Tph2 mRNA, TPH2 protein and regional levels of 5-HT and its metabolite 5-hydroxyindoleacetic acid. Tph2 mRNA and TPH2 protein in brainstem dorsal raphe nuclei was assayed by in situ hybridization and immunocytochemistry respectively. 5-HT and 5-hydroxyindoleacetic acid were determined by HPLC. BALB/cJ mice had 20% less Tph2 mRNA and 28% fewer TPH2 immunolabeled neurons than C57Bl/6J mice (t = -2.59, p = 0.02). The largest difference in Tph2 transcript expression was in rostral dorsal raphe nuclei (t = 2.731, p = 0.008). 5-HT was 15% lower in the midbrain and 18% lower in the cerebral cortex of BALB/cJ compared with C57Bl/6J mice (p < 0.05). The behavioral differences in BALB/cJ mice relative to the C57Bl/6J strain may be due in part, to fewer 5-HT neurons and lower Tph2 gene expression resulting in less 5-HT neurotransmission. Future studies quantifying expression per neuron are needed to determine whether less expression is explained by fewer neurons or also less expression per neuron, or both.
authors: Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, New York 10032, USA. hb2104@columbia.edu
authors: Helene
authors: H
authors: Bach
authors: Victoria
authors: V
authors: Arango
authors: Yung-Yu
authors: YY
authors: Huang
authors: Sharlene
authors: S
authors: Leong
authors: J John
authors: JJ
authors: Mann
authors: Mark D
authors: MD
authors: Underwood
mesh_terms: D000818:Animals; D001345:Autoradiography; D001923:Brain Chemistry; D002452:Cell Count; D003720:Densitometry; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000201:enzymology*; D011903:Raphe Nuclei / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D013045:Species Specificity; D014365:Tryptophan Hydroxylase / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; C487802:Tph2 protein, mouse; D014365:Tryptophan Hydroxylase