scholarly journals Regulation of Serine (Ser)-31 and Ser40 Tyrosine Hydroxylase Phosphorylation during Morphine Withdrawal in the Hypothalamic Paraventricular Nucleus and Nucleus Tractus Solitarius-A2 Cell Group: Role of ERK1/2

Endocrinology ◽  
2007 ◽  
Vol 148 (12) ◽  
pp. 5780-5793 ◽  
Author(s):  
Cristina Núñez ◽  
M. Luisa Laorden ◽  
M. Victoria Milanés
Keyword(s):  
Tyrosine Hydroxylase ◽  
Paraventricular Nucleus ◽  
Nucleus Tractus Solitarius ◽  
Morphine Withdrawal ◽  
Hypothalamic Paraventricular Nucleus ◽  
Cell Group ◽  
Erk Activation ◽  
Catecholamine Biosynthesis ◽  
Hpa Axis Activity

Our previous studies have shown that naloxone-induced morphine withdrawal increases the hypothalamic-pituitary-adrenocortical (HPA) axis activity, which is dependent on a hyperactivity of noradrenergic pathways [nucleus tractus solitarius (NTS) A2] innervating the hypothalamic paraventricular nucleus (PVN). Short-term regulation of catecholamine biosynthesis occurs through phosphorylation of tyrosine hydroxylase (TH), which enhances enzymatic activity. In the present study, the effect of morphine withdrawal on site-specific TH phosphorylation in the PVN and NTS-A2 was determined by quantitative blot immunolabeling and immunohistochemistry using phosphorylation state-specific antibodies. We show that naloxone-induced morphine withdrawal phosphorylates TH at Serine (Ser)-31 but not Ser40 in PVN and NTS-A2, which is associated with both an increase in total TH immunoreactivity in NTS-A2 and an enhanced TH activity in the PVN. In addition, we demonstrated that TH neurons phosphorylated at Ser31 coexpress c-Fos in NTS-A2. We then tested whether pharmacological inhibition of ERK activation by ERK kinase contributes to morphine withdrawal-induced phosphorylation of TH at Ser31. We show that the ability of morphine withdrawal to stimulate phosphorylation at this seryl residue is reduced by SL327, an inhibitor of ERK1/2 activation. These results suggest that morphine withdrawal increases noradrenaline turnover in the PVN, at least in part, via ERK1/2-dependent phosphorylation of TH at Ser31.

scholarly journals Elevated Glucocorticoid Levels Are Responsible for Induction of Tyrosine Hydroxylase mRNA Expression, Phosphorylation, and Enzyme Activity in the Nucleus of the Solitary Tract during Morphine Withdrawal

Endocrinology ◽  
2009 ◽  
Vol 150 (7) ◽  
pp. 3118-3127 ◽  
Author(s):  
Cristina Núñez ◽  
Anna Földes ◽  
Domingo Pérez-Flores ◽  
J. Carlos García-Borrón ◽  
M. Luisa Laorden ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Tyrosine Hydroxylase ◽  
Mrna Expression ◽  
Morphine Withdrawal ◽  
Morphine Dependence ◽  
Cell Group ◽  
Solitary Tract ◽  
Catecholamine Biosynthesis ◽  
Protein Levels ◽  
Noradrenergic Pathway

Chronic opiate exposure induces neurochemical adaptations in the noradrenergic system. Enhanced responsiveness of the hypothalamo-pituitary-adrenal axis after morphine withdrawal has been associated with hyperactivity of ascending noradrenergic input from the nucleus of the solitary tract (NTS-A2) cell group to the hypothalamic paraventricular nucleus (PVN). This study addressed the role of morphine withdrawal-induced corticosterone (CORT) release in regulation of tyrosine hydroxylase (TH), the rate-limiting enzyme of catecholamine biosynthesis in adrenalectomized (ADX) rats supplemented with low CORT pellet (ADX plus CORT). Present results show that in sham-ADX rats, noradrenergic neurons in the NTS-A2 became activated during morphine withdrawal, as indicated by increased TH mRNA expression. However, this induction of TH expression is not detected in ADX plus CORT rats that are unable to mount CORT secretory response to morphine withdrawal. Total TH protein levels were elevated in the NTS-A2 from sham-operated rats during morphine dependence and withdrawal, whereas we did not find any alteration in ADX plus CORT animals. Furthermore, high levels of TH phosphorylated (activated) at Ser31 (but not at Ser40) were found in the A2 area from sham-morphine withdrawn rats. Consistent with these effects, we observed an increase in the enzyme activity of TH in the PVN. However, induction of morphine withdrawal to ADX plus CORT animals did not alter the phosphorylation (activation) of TH in NTS-A2 and decreased TH activity in the PVN. These results suggest the existence of a positive reverberating circle in which elevated glucocorticoids during morphine abstinence play a permissive role in morphine withdrawal-induced activation of noradrenergic pathway innervating the PVN.

Effects of rolipram and diazepam on the adaptive changes induced by morphine withdrawal in the hypothalamic paraventricular nucleus

2009 ◽  
Vol 620 (1-3) ◽  
pp. 1-8 ◽  
Author(s):  
Cristina Núñez ◽  
Ana González-Cuello ◽  
Lorenzo Sánchez ◽  
M. Luisa Vargas ◽  
M. Victoria Milanés ◽  
...  
Keyword(s):  
Paraventricular Nucleus ◽  
Morphine Withdrawal ◽  
Hypothalamic Paraventricular Nucleus ◽  
Adaptive Changes

scholarly journals The role of SOCS3 in the hypothalamic paraventricular nucleus in rat model of inflammatory pain

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Na Meng ◽  
Ning-Ning Ji ◽  
Ziming Zhou ◽  
Yicheng Qian ◽  
Yu Tang ◽  
...  
Keyword(s):  
Paraventricular Nucleus ◽  
Rat Model ◽  
Inflammatory Pain ◽  
Hypothalamic Paraventricular Nucleus

scholarly journals Acute hypoxia activates neuroendocrine, but not presympathetic, neurons in the paraventricular nucleus of the hypothalamus: differential role of nitric oxide

2017 ◽  
Vol 312 (6) ◽  
pp. R982-R995 ◽  
Author(s):  
K. Max Coldren ◽  
De-Pei Li ◽  
David D. Kline ◽  
Eileen M. Hasser ◽  
Cheryl M. Heesch
Keyword(s):  
Nitric Oxide ◽  
Paraventricular Nucleus ◽  
Median Eminence ◽  
Nucleus Tractus Solitarius ◽  
Acute Hypoxia ◽  
Ventrolateral Medulla ◽  
Specific Cell ◽  
External Zone ◽  
Cell Phenotypes

Hypoxia results in decreased arterial Po2, arterial chemoreflex activation, and compensatory increases in breathing, sympathetic outflow, and neuroendocrine secretions, including increased secretion of AVP, corticotropin-releasing hormone (CRH), adrenocorticotropin hormone (ACTH), and corticosterone. In addition to a brain stem pathway, including the nucleus tractus solitarius (nTS) and the rostral ventrolateral medulla (RVLM), medullary pathways to the paraventricular nucleus of the hypothalamus (PVN) contribute to chemoreflex responses. Experiments evaluated activation of specific cell phenotypes within the PVN following an acute hypoxic stimulus (AH; 2 h, 10% O2) in conscious rats. Retrograde tracers (from spinal cord and RVLM) labeled presympathetic (PreS) neurons, and immunohistochemistry identified AVP- and CRH-immunoreactive (IR) cells. c-Fos-IR was an index of neuronal activation. Hypoxia activated AVP-IR (~6%) and CRH-IR (~15%) cells, but not PreS cells in the PVN, suggesting that sympathoexcitation during moderate AH is mediated mainly by a pathway that does not include PreS neurons in the PVN. Approximately 14 to 17% of all PVN cell phenotypes examined expressed neuronal nitric oxide synthase (nNOS-IR). AH activated only nNOS-negative AVP-IR neurons. In contrast ~23% of activated CRH-IR neurons in the PVN contained nNOS. In the median eminence, CRH-IR terminals were closely opposed to tanycyte processes and end-feet (vimentin-IR) in the external zone, where vascular NO participates in tanycyte retraction to facilitate neuropeptide secretion into the pituitary portal circulation. Results are consistent with an inhibitory role of NO on AVP and PreS neurons in the PVN and an excitatory role of NO on CRH secretion in the PVN and median eminence.

scholarly journals Ascending Brainstem Pathways Are Not Involved in Lipopolysaccharide-Induced Suppression of Thyrotropin-Releasing Hormone Gene Expression in the Hypothalamic Paraventricular Nucleus

Endocrinology ◽  
2005 ◽  
Vol 146 (3) ◽  
pp. 1357-1363 ◽  
Author(s):  
Csaba Fekete ◽  
Praful S. Singru ◽  
Sumit Sarkar ◽  
William M. Rand ◽  
Ronald M. Lechan
Keyword(s):  
Gene Expression ◽  
Paraventricular Nucleus ◽  
Hypothalamic Paraventricular Nucleus ◽  
Nonthyroidal Illness ◽  
Intact Side ◽  
In Situ Hybridization Histochemistry ◽  
Immunocytochemical Detection ◽  
Lps Treatment

The nonthyroidal illness syndrome associated with fasting, infection, and chronic illness is characterized by low thyroid hormone levels and low or inappropriately normal TSH levels in circulating blood and reduced synthesis of TRH in hypophysiotropic neurons residing in the hypothalamic paraventricular nucleus (PVN). To test the hypothesis that ascending brainstem pathways are involved in mediation of bacterial lipopolysaccharide (LPS)-induced suppression of TRH mRNA in the PVN, we unilaterally transected brainstem pathways to the PVN and determined the effects of LPS on TRH gene expression and, as a control, on CRH gene expression in hypophysiotropic neurons using semiquantitative in situ hybridization histochemistry. The efficacy of the transection was determined by immunocytochemical detection of ascending adrenergic pathways in the PVN. In vehicle-treated animals, CRH mRNA in the PVN showed a significant reduction on the transected side compared with the intact side, whereas a significant increase in TRH mRNA was observed on the transected side compared with the intact side. After LPS administration (250 μg/100 g body weight), a dramatic increase in CRH mRNA was observed on the intact side, and a significantly lesser increase was found on the transected side. In contrast, LPS treatment resulted in reduction in TRH mRNA on the transected side compared with the intact side and a significant reduction in TRH mRNA on the transected side compared with vehicle-treated animals. These studies confirm an important role of ascending brainstem projections in LPS-induced activation of CRH gene expression, but indicate that they do not mediate the effect of LPS to inhibit hypophysiotropic TRH gene expression.

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