The Distribution and Neurochemistry of the Parathyroid Hormone 2 Receptor in the Rat Hypothalamus

Dobolyi, Árpád; Irwin, Sarah; Wang, Jing; Usdin, Ted B.

doi:10.1007/s11064-005-9011-9

Cited by 24 publications

(57 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In several brain regions, PTH2Rs have been shown to be located on glutamatergic nerve terminals (11,19). We found that this colocalization is also the case in the LC area.…”

Section: Resultssupporting

confidence: 65%

Neuropathic and inflammatory pain are modulated by tuberoinfundibular peptide of 39 residues

Dimitrov

Kuo

Kohno

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Nociceptive information is modulated by a large number of endogenous signaling agents that change over the course of recovery from injury. This plasticity makes understanding regulatory mechanisms involved in descending inhibition of pain scientifically and clinically important. Neurons that synthesize the neuropeptide TIP39 project to many areas that modulate nociceptive information. These areas are enriched in its receptor, the parathyroid hormone 2 receptor (PTH2R). We previously found that TIP39 affects several acute nociceptive responses, leading us to now investigate its potential role in chronic pain. Following nerve injury, both PTH2R and TIP39 knockout mice developed less tactile and thermal hypersensitivity than controls and returned to baseline sensory thresholds faster. Effects of hindpaw inflammatory injury were similarly decreased in knockout mice. Blockade of α-2 adrenergic receptors increased the tactile and thermal sensitivity of apparently recovered knockout mice, returning it to levels of neuropathic controls. Mice with locus coeruleus (LC) area injection of lentivirus encoding a secreted PTH2R antagonist had a rapid, α-2 reversible, apparent recovery from neuropathic injury similar to the knockout mice. Ablation of LC area glutamatergic neurons led to local PTH2R-ir loss, and barley lectin was transferred from local glutamatergic neurons to GABA interneurons that surround the LC. These results suggest that TIP39 signaling modulates sensory thresholds via effects on glutamatergic transmission to brainstem GABAergic interneurons that innervate noradrenergic neurons. TIP39's normal role may be to inhibit release of hypoalgesic amounts of norepinephrine during chronic pain. The neuropeptide may help maintain central sensitization, which could serve to enhance guarding behavior.supraspinal pain | allodynia | partial sciatic nerve ligation | Freund's adjuvant

show abstract

“…In several brain regions, PTH2Rs have been shown to be located on glutamatergic nerve terminals (11,19). We found that this colocalization is also the case in the LC area.…”

Section: Resultssupporting

confidence: 65%

Neuropathic and inflammatory pain are modulated by tuberoinfundibular peptide of 39 residues

Dimitrov

Kuo

Kohno

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Every fourth free-floating section was first stained for TIP39 using FITC-tyramide amplification fluorescent immunocytochemistry. An affinity-purified antiserum from a rabbit immunized with rat TIP39, which can be absorbed with synthetic TIP39 (Dobolyi et al 2002), and labels cell bodies with the same distribution as observed by in situ hybridization histochemistry (Dobolyi et al 2006a, b), was used as primary antiserum. This antiserum (1:3000) was applied for 48 h at room temperature, followed by incubation of the sections in biotinylated donkey anti-rabbit secondary antibody (1:1000; Jackson ImmunoResearch), then in ABC complex (1:500; Vector Laboratories) for 2 h. Sections were subsequently incubated with FITC-tyramide (1:8000) and H 2 O 2 in Tris hydrochloride buffer (0.1 M, pH 8.0) for 6 min.…”

Section: Methodsmentioning

confidence: 99%

Maternally involved galanin neurons in the preoptic area of the rat

et al. 2016

Self Cite

View full text Add to dashboard Cite

Recent selective stimulation and ablation of galanin neurons in the preoptic area of the hypothalamus established their critical role in control of maternal behaviors. Here, we identified a group of galanin neurons in the anterior commissural nucleus (ACN), and a distinct group in the medial preoptic area (MPA). Galanin neurons in ACN but not the MPA co-expressed oxytocin. We used immunodetection of phosphorylated STAT5 (pSTAT5), involved in prolactin receptor signal transduction, to evaluate the effects of suckling-induced prolactin release and found that 76 % of galanin cells in ACN, but only 12 % in MPA were prolactin responsive. Nerve terminals containing tuberoinfundibular peptide 39 (TIP39), a neuropeptide that mediates effects of suckling on maternal motivation, were abundant around galanin neurons in both preoptic regions. In the ACN and MPA, 89 and 82 % of galanin neurons received close somatic appositions, with an average of 2.9 and 2.6 per cell, respectively. We observed perisomatic innervation of galanin neurons using correlated light and electron microscopy. The connection was excitatory based on the glutamate content of TIP39 terminals demonstrated by post-embedding immunogold electron microscopy. Injection of the anterograde tracer biotinylated dextran amine into the TIP39-expressing posterior intralaminar complex of the thalamus (PIL) demonstrated that preoptic TIP39 fibers originate in the PIL, which is activated by suckling. Thus, galanin neurons in the preoptic area of mother rats are innervated by an excitatory neuronal pathway that conveys suckling-related information. In turn, they can be topographically and neurochemically divided into two distinct cell groups, of which only one is affected by prolactin.

show abstract

“…Free-floating sections were then pretreated with 1% bovine serum albumin in PBS containing 0.6% Triton X-100 for 30 min at room temperature. The sections were then placed in anti-TIP39 primary antiserum (1:3000 for tyramide amplification and 1:600 for DAB reaction) for 48 hours at room temperature or anti-PTH2 receptor primary antiserum (1:60000 for tyramide amplification and 1:15000 for DAB reaction) for 24 hours at room temperature as described previously (Dobolyi et al, 2006;Usdin et al, 1999a;Usdin et al, 1999b;Wang et al, 2000). The sections were then incubated in biotinylated anti-rabbit secondary antibody (1:600 dilution; Vector Laboratories, Burlingame, CA) for 2 hours followed by incubation in a solution containing avidin-biotin-peroxidase complex (1:150; Vector Laboratories, Burlingame, CA) for 2 hours.…”

Section: Immunocytochemistrymentioning

confidence: 99%

“…The distributions of TIP39 fibers (Dobolyi et al, 2003b) and the PTH2 receptor in the central nervous system have recently been described in young male rats. PTH2 receptors and TIP39 fibers have similar distributions in many brain regions, suggesting that they form a neuromodulator system (Dobolyi et al, 2006). TIP39 fibers and PTH2 receptors are abundant in the medial prefrontal cortex, the lateral septum, the amygdala, several different hypothalamic nuclei, the paraventricular thalamic nucleus, and the parabrachial nuclei (Dobolyi et al, 2006;Dobolyi et al, 2003b;Wang et al, 2000) suggesting limbic-endocrine functions for TIP39 (Dobolyi et al, 2003a;Usdin et al, 2003).…”

Section: Introductionmentioning

confidence: 98%

“…PTH2 receptors and TIP39 fibers have similar distributions in many brain regions, suggesting that they form a neuromodulator system (Dobolyi et al, 2006). TIP39 fibers and PTH2 receptors are abundant in the medial prefrontal cortex, the lateral septum, the amygdala, several different hypothalamic nuclei, the paraventricular thalamic nucleus, and the parabrachial nuclei (Dobolyi et al, 2006;Dobolyi et al, 2003b;Wang et al, 2000) suggesting limbic-endocrine functions for TIP39 (Dobolyi et al, 2003a;Usdin et al, 2003). Initial functional studies suggest that TIP39 is involved in the transmission of nociceptive information towards higher nociceptive centers (Dobolyi et al, 2002;.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Postnatal development and gender‐dependent expression of TIP39 in the rat brain

Dobolyi

Wang

Irwin

et al. 2006

J of Comparative Neurology

Self Cite

View full text Add to dashboard Cite

Tuberoinfundibular peptide of 39 residues (TIP39) is a selective agonist of the parathyroid hormone 2 (PTH2) receptor. The topographical distributions of TIP39 and the PTH2 receptor in the brain, described in young male rats, suggested that TIP39 has limbic and endocrine functions. In the present study, we investigated the expression of TIP39 and the PTH2 receptor in male and female rat brain during postnatal development by means of in situ hybridization histochemistry, quantitative RT-PCR and immunocytochemistry. TIP39's distribution and expression levels are similar in young female and male brains. TIP39 mRNA levels peak at postnatal day 14 and subsequently decline both in the subparafascicular area and the medial paralemniscal nucleus, the two major sites where TIP39 is synthesized. A greater developmental decrease in TIP39 expression in males leads to greater levels in older females than older males. The decrease is partially reversed by pre-pubertal but not post-pubertal gonadectomy. TIP39 peptide levels in cell bodies change in parallel with mRNA levels, while TIP39 appears and disappears somewhat later in nerve fibers. In addition, TIP39 peptide levels are also sexually dimorphic in older rats. In contrast, PTH2 receptor expression in the brain does not decrease during puberty and is not sexually dimorphic even in old animals. The appearance of TIP39 during early, and decline during late, postnatal development together with the gender dependent levels in mature animals suggest that TIP39 may play a role in sexual maturation or gender specific functions. Indexing termstuberoinfundibular peptide of 39 residues; parathyroid hormone 2 receptor; TIP39 and PTH2 receptor in situ hybridization and immunocytochemistry and quantitative

show abstract

The Distribution and Neurochemistry of the Parathyroid Hormone 2 Receptor in the Rat Hypothalamus

Cited by 24 publications

References 30 publications

Neuropathic and inflammatory pain are modulated by tuberoinfundibular peptide of 39 residues

Neuropathic and inflammatory pain are modulated by tuberoinfundibular peptide of 39 residues

Maternally involved galanin neurons in the preoptic area of the rat

Postnatal development and gender‐dependent expression of TIP39 in the rat brain

Contact Info

Product

Resources

About