Estrogen Selectively Increases Tryptophan Hydroxylase-2 mRNA Expression in Distinct Subregions of Rat Midbrain Raphe Nucleus: Association between Gene Expression and Anxiety Behavior in the Open Field

Hiroi, Ryoko; McDevitt, Ross A.; Neumaier, John F.

doi:10.1016/j.biopsych.2005.10.019

Cited by 139 publications

(122 citation statements)

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“…In ovariectomized rats, estrogen increased TPH2 expression only in mid-and caudal regions of the DRN and was correlated with decreased anxiety behaviors. 38 In stress-sensitive female monkeys, SERT mRNA was found to be decreased specifically in the caudal subnucleus. 39 Although 5-HT levels were not measured in these studies, both of these findings are consistent with a compensatory response to deficient serotonergic neurotransmission.…”

Section: Discussionmentioning

confidence: 96%

Elevated expression of tryptophan hydroxylase-2 mRNA at the neuronal level in the dorsal and median raphe nuclei of depressed suicides

et al. 2008

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Deficient levels of serotonin are associated with suicide and depression. Paradoxically, in the dorsal raphe nucleus (DRN) there are more serotonin neurons and more neuronal tryptophan hydroxylase-2 (TPH2) expression postmortem in depressed suicides. In this study, we sought to determine whether greater TPH2 expression in depressed suicides was the result of more TPH2 expression per neuron. In situ hybridization and computer-assisted image analysis were performed on tissue sections throughout the extent of the raphe nuclei at the level of silver grains per neuron to systematically quantify TPH2 neuronal expression. Depressed suicides have 26.5% more TPH2 grain density per neuron in the DRN compared with matched controls (P = 0.04). The difference in grain density is greater at mid-and caudal anatomical levels across the rostrocaudal axis of the DRN. Densitometric analysis of TPH2 expression in the DRN subnuclei showed that higher expression levels were observed at posterior anatomical levels of depressed suicides (121% of control in the caudal subnucleus). Higher TPH2 expression in depressed suicides may explain more TPH2 protein and reflect a homeostatic response to deficient serotonin levels in the brains of depressed suicides. Localized changes in TPH2 expression in specific subnuclei of the DRN suggest that the serotonergic compensatory mechanism in depression and suicide is specifically regulated within the DRN and has implications for regions innervated by this subnucleus.

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Section: Discussionmentioning

confidence: 96%

Elevated expression of tryptophan hydroxylase-2 mRNA at the neuronal level in the dorsal and median raphe nuclei of depressed suicides

et al. 2008

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“…This response was expected based on most earlier studies of ambulatory activity in E2-treated ovariectomized female rodents Pfaff, 2001, 2002;Morgan et al, 2004;Segarra et al, 2010). The fact that some studies did not find an inhibitory effect of E2 on open-field locomotion in ovariectomized rodents may reflect the treatment paradigms used and E2 levels obtained (Ogawa et al, 2003;Hiroi et al, 2006;Walf et al, 2008). The decrease in mobility caused by E2 treatment would be expected to have an impact on several behavioral tests.…”

Section: Discussionmentioning

confidence: 70%

Analysis of Kalirin-7 Knockout Mice Reveals Different Effects in Female Mice

et al. 2012

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Estradiol treatment of ovariectomized rodents is known to affect the morphology of dendritic spines and produce behavioral and cognitive effects. Kalirin-7 (Kal7), a postsynaptic density (PSD)-localized Rho-guanine nucleotide exchange factor, is important for dendritic spine formation and stability. Male Kal7 knockout [Kal7(KO)] mice exhibit a number of abnormal behavioral and biochemical phenotypes. Given that chronic 17␤-estradiol (E2) replacement of ovariectomized rats enhanced Kal7 expression in the hippocampus and primary hippocampal cultures, we assessed the behavioral and biochemical effects of chronic E2 treatment of ovariectomized female wild-type and Kal7(KO) mice. Both intact and ovariectomized Kal7(KO) female mice exhibited decreased anxiety-like behavior compared with the corresponding wild type in the elevated zero maze and were unaffected by E2 treatment. Chronic E2 decreased locomotor activity in the open field and enhanced performance in a passive-avoidance fear conditioning task, which were both unaffected by genotype. Kal7(KO) female mice engaged in significantly more object exploration, both familiar and novel, than did wild-type females. E2 enhanced the acute locomotor response to cocaine, with no significant effect of genotype. Similar to Kal7(KO) males, Kal7(KO) females had decreased levels of Nmethyl-D-aspartate receptor 2B in hippocampal PSD fractions with no effect of E2 treatment. The differing behavioral effects of Kal7 ablation in female and male mice may offer insight into the molecular underpinnings of these differences.

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“…Particularly, activity and expression of enzymes that synthesize and metabolize DA, NE and 5-HT are altered by E2 (Babu and Vijayan, 1984;Chaube and Joy, 2011;Donner and Handa, 2009;Luine and Rhodes, 1983;Luine et al, 1973;Rahman and Thomas, 2013;Scardapane and Cardinali, 1977;Schendzielorz et al, 2011;Serova et al, 2002). In addition, E 2 increases mRNA levels and activity of TH and TRH, the major rate limiting enzymes in catecholamines and indoleamines biosynthesis, respectively (Babu and Vijayan, 1984;Chaube and Joy, 2011;Rahman and Thomas, 2013;Serova et al, 2002;Donner and Handa, 2009;Aggarwal et al, 2012;Hiroi et al, 2006). Alternatively, it decreases MAO mRNA levels (Aggarwal et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Amitraz changes NE, DA and 5-HT biosynthesis and metabolism mediated by alterations in estradiol content in CNS of male rats

et al. 2017

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(2017). Amitraz changes NE, DA and 5-HT biosynthesis and metabolism mediated by alterations in estradiol content in CNS of male rats. Chemosphere, 181 518-529. Amitraz is a formamidine insecticide/acaricide that alters different neurotransmitters levels, among other neurotoxic effects. Oral amitraz exposure (20, 50 and 80 mg/kg bw, 5 days) has been reported to increase serotonin (5-HT), norepinephrine (NE) and dopamine (DA) content and to decrease their metabolites and turnover rates in the male rat brain, particularly in the striatum, prefrontal cortex, and hippocampus. However, the mechanisms by which these alterations are produced are not completely understood. One possibility is that amitraz monoamine oxidase (MAO) inhibition could mediate these effects. Alternatively, it alters serum concentrations of sex steroids that regulate the enzymes responsible for these neurotransmitters synthesis and metabolism. Thus, alterations in sex steroids in the brain could also mediate the observed effects. To test these hypothesis regarding possible mechanisms, we treated male rats with 20, 50 and 80 mg/kg bw for 5 days and then isolated tissue from striatum, prefrontal cortex, and hippocampus. We then measured tissue levels of expression and/or activity of MAO, catechol-O-metyltransferase (COMT), dopamine-b-hydroxylase (DBH), tyrosine hydroxylase (TH) and tryptophan hydroxylase (TRH) as well as estradiol levels in these regions. Our results show that amitraz did notAbbreviations: AD, aldehyde dehydrogenase; AMZ, amitraz; ARO, aromatase; AAADC, aromatic amino acid decarboxylase; CNS, central nervous system; COMT, catechol-O-metyltransferase; Ct, cycle threshold; DA, dopamine; DBH, dopamine-bhydroxylase; DOPA, 3,4-dihydroxyphenylalanine; DOPAC, 3,4-hydroxyphenylacetic acid; DHT, dihydrotestosterone; E2, 17b-estradiol; FC, prefrontal cortex; HC, hippocampus; HPLC, high performance liquid chromatography; HVA, homovanillic acid; 5-HT, serotonin; 5-HTP, 5-hydroxytryptophan; 5-HIAA, 5-hydroxy-3-indolacetic acid; LD 50 , Lethal Dose 50; LOQ, Quantification limit; MAO, monoamine oxidase; MHPG, 3-metoxy-4-hydroxyphenylethyleneglycol; NE, norepinephrine; NSD-1015, m-hydroxymethylhydrazine; SD, standard deviation; ST, striatum; T, testosterone; TH, tyrosine hydroxylase; TMX, tamoxifen; TRH, tryptophan hydroxylase.* Chemosphere 181 (2017) 518e529 inhibit MAO activity at these doses, but altered MAO, COMT, DBH, TH and TRH gene expression, as well as TH and TRH activity and estradiol levels. The alteration of these enzymes was partially mediated by dysregulation of estradiol levels. Our present results provide new understanding of the mechanisms contributing to the harmful effects of amitraz.

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Estrogen Selectively Increases Tryptophan Hydroxylase-2 mRNA Expression in Distinct Subregions of Rat Midbrain Raphe Nucleus: Association between Gene Expression and Anxiety Behavior in the Open Field

Cited by 139 publications

References 73 publications

Elevated expression of tryptophan hydroxylase-2 mRNA at the neuronal level in the dorsal and median raphe nuclei of depressed suicides

Elevated expression of tryptophan hydroxylase-2 mRNA at the neuronal level in the dorsal and median raphe nuclei of depressed suicides

Analysis of Kalirin-7 Knockout Mice Reveals Different Effects in Female Mice

Amitraz changes NE, DA and 5-HT biosynthesis and metabolism mediated by alterations in estradiol content in CNS of male rats

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