Thyrotropin-Releasing Hormone Receptor 1-Deficient Mice Display Increased Depression and Anxiety-Like Behavior

Zeng, Hongkui; Schimpf, Brian A.; Rohde, Alex; Pavlova, Maria N.; Gragerov, Alexander; Bergmann, John E.

doi:10.1210/me.2007-0048

Cited by 64 publications

(49 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was not a goal of this study to characterize the effects of deleting both TRH receptor subtypes in mice in the absence of TRH analog administration. Previous reports have described effects on CNS function in R1ko (Zeng et al, 2007) and R2ko mice (Sun et al, 2009). R1ko were found to exhibit increased depression-like and increased anxiety-like behaviors whereas female, but not male, R2/ko mice exhibited moderately increased depression-like and reduced anxiety-like phenotypes.…”

Section: Discussionmentioning

confidence: 93%

“…We studied previously reported TRH-R1 knockout (R1ko) (Zeng et al, 2007) and R2ko mice (Sun et al, 2009), and newly generated R1/R2ko mice and compared them to WT mice. TRH-R1 and TRH-R2 mRNA levels were similar in WT brains ( Figure 2).…”

Section: Resultsmentioning

confidence: 99%

“…These findings suggest that TRH-R1 may be involved in maintaining a conscious state under normal physiological conditions. Also, R1ko mice were found to be mildly hypothyroid (Zeng et al, 2007), and this may have affected basal sleeping time in R1ko and R1/R2ko animals given pentobarbital. Of note for this study, however, is that the pharmacologic effects of TRH on pentobarbital-induced sedation are not affected by hypothyroidism (Breese et al, 1975).…”

Section: Discussionmentioning

confidence: 99%

“…TRH-R1 þ / À male mice in 129S1/SvImJ background were obtained (Omeros Corporation, Seattle, WA) and bred with WT 129S1/SvImJ females. Resulting heterozygous mice were bred to obtain homozygous TRH-R1 À / À (R1ko) mice (Zeng et al, 2007). TRH-R2-deficient (R2ko) mice in a mixed 129/Svev background were generated and bred as reported (Sun et al, 2009).…”

Section: Mouse Studiesmentioning

confidence: 99%

See 3 more Smart Citations

Thyrotropin-Releasing Hormone Receptor Type 1 (TRH-R1), not TRH-R2, Primarily Mediates Taltirelin Actions in the CNS of Mice

Thirunarayanan

Nir

Raaka

et al. 2012

Neuropsychopharmacol

View full text Add to dashboard Cite

Thyrotropin-releasing hormone receptor type 2 (TRH-R2), not TRH-R1, has been proposed to mediate the CNS effects of TRH and its more effective analog taltirelin (TAL). Consistent with this idea, TAL exhibited higher binding affinity and signaling potency at mouse TRH-R2 than TRH-R1 in a model cell system. We used TRH-R1 knockout (R1ko), R2ko and R1/R2ko mice to determine which receptor mediates the CNS effects of TAL. There was no TRH-R1 mRNA in R1ko and R1/R2ko mice and no TRH-R2 mRNA in R2ko and R1/R2ko mice. Specific [ 3 H]MeTRH binding to whole brain membranes was 5% of wild type (WT) for R1ko mice, 100% for R2ko mice and 0% for R1/R2ko mice, indicating TRH-R1 is the predominant receptor expressed in the brain. In arousal assays, TAL shortened sleep time with pentobarbital sedation in WT and R2ko mice by 44 and 49% and with ketamine/xylazine sedation by 66 and 55%, but had no effect in R1ko and R1/R2ko mice. In a tail flick assay of nociception, TAL increased response latency by 65 and 70% in WT and R2ko mice, but had no effect in R1ko and R1/R2ko mice. In a tail suspension test of depression-like behavior, TAL increased mobility time by 49 and 37% in WT and R2ko mice, but had no effect in R1ko and R1/R2ko mice. Thus, in contrast to the generally accepted view that the CNS effects of TAL are mediated by TRH-R2, these effects are mediated primarily if not exclusively by TRH-R1 in mice. Neuropsychopharmacology (2013) 38, 950-956;

show abstract

Section: Discussionmentioning

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Mouse Studiesmentioning

confidence: 99%

See 2 more Smart Citations

Thyrotropin-Releasing Hormone Receptor Type 1 (TRH-R1), not TRH-R2, Primarily Mediates Taltirelin Actions in the CNS of Mice

Thirunarayanan

Nir

Raaka

et al. 2012

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…TRH-R1 knock-out mice showed central dysfunction of HPT axis, mild hyperglycemia and only slight changes in growth, body weight and food intake. In these animals, an increased level of depressive and anxiogenic behavior was observed [56]. In contrast, in TRH-R2 knock-outs, neither the function of the HPT axis, metabolism of glucose, development nor growth were disturbed when compared to wild type mice.…”

Section: Stimulatory Effects Of Trh In the Cns And Its Potential Clinmentioning

confidence: 88%

Tyreoliberin (Trh) – The Regulatory Neuropeptide of Cns Homeostasis

Jantas¹

2010

Advances in Cell Biology

View full text Add to dashboard Cite

Summary:The physiological role of thyreoliberin (TRH) is the preservation of homeostasis within four systems (i) the hypothalamic-hypophsysiotropic neuroendocrine system, (ii) the brain stem/midbrain/spinal cord system, (iii) the limbic/cortical system, and (iv) the chronobiological system. Thus TRH, via various cellular mechanisms, regulates a wide range of biological processes (arousal, sleep, learning, locomotive activity, mood) and possesses the potential for unique and widespread applications for treatment of human illnesses. Since the therapeutic potential of TRH is limited by its pharmacological profile (enzymatic instability, short half-life, undesirable effects), several synthetic analogues of TRH were constructed and studied in mono-or adjunct therapy of central nervous system (CNS) disturbances. The present article summarizes the current state of understanding of the physiological role of TRH and describes its putative role in clinical indications in CNS maladies with a focus on the action of TRH analogues.

show abstract

Efferent projections of thyrotropin‐releasing hormone‐synthesizing neurons residing in the anterior parvocellular subdivision of the hypothalamic paraventricular nucleus

Wittmann¹,

Füzesi²,

Singru³

et al. 2009

J of Comparative Neurology

View full text Add to dashboard Cite

The anterior parvocellular subdivision of the PVN (aPVN) contains non-hypophysiotropic TRH neurons that are densely innervated by feeding-related neuronal groups of the hypothalamic arcuate nucleus. To determine how these TRH neurons are integrated within the brain, the major projection fields of this cell group was studied by anterograde and retrograde tract-tracing methods. Projection sites were identified by injection of the anterograde tracer Phaseolus vulgaris leuco-agglutinin (PHAL) into the aPVN, and subsequent double immunofluorescent staining was used to visualize axons containing both PHAL and proTRH. To distinguish between the projection sites of TRH neurons residing in the aPVN and the closely situated perifornical area. the retrograde tracer, cholera toxin B subunit (CTB), was injected into regions where PHAL/proTRHcontaining axons were densely accumulated. TRH neurons in the aPVN were found to project to the hypothalamic arcuate, dorsomedial and ventral premammillary nuclei, medial preoptic region, tuber cinereum area, paraventricular thalamic nucleus, bed nucleus of the stria terminalis, lateral septal nucleus and central amygdaloid nucleus. Projection fields of perifornical TRH neurons were in partial overlap with that of the aPVN TRH cells. In addition, these neurons also innervated the hypothalamic ventromedial nucleus, the medial amygdaloid nucleus and the amygdalohippocampal area. These data suggest that through its efferent connections, aPVN TRH neurons may be involved in the regulation of energy homeostasis co-ordinately with effects on behavior, locomotor activity and thermogenesis. In addition, the major differences in the projection fields of aPVN and perifornical TRH neurons suggest that these two TRH-synthesizing neuronal groups are functionally different.

show abstract

Thyrotropin-Releasing Hormone Receptor 1-Deficient Mice Display Increased Depression and Anxiety-Like Behavior

Cited by 64 publications

References 50 publications

Thyrotropin-Releasing Hormone Receptor Type 1 (TRH-R1), not TRH-R2, Primarily Mediates Taltirelin Actions in the CNS of Mice

Thyrotropin-Releasing Hormone Receptor Type 1 (TRH-R1), not TRH-R2, Primarily Mediates Taltirelin Actions in the CNS of Mice

Tyreoliberin (Trh) – The Regulatory Neuropeptide of Cns Homeostasis

Efferent projections of thyrotropin‐releasing hormone‐synthesizing neurons residing in the anterior parvocellular subdivision of the hypothalamic paraventricular nucleus

Contact Info

Product

Resources

About