Cyclic adenosine monophosphate differentiated β-endorphin neurons promote immune function and prevent prostate cancer growth

Sarkar, Dipak K.; Boyadjieva, Nadka; Chen, Cui Ping; Ortigüela, María; Reuhl, Kenneth R.; Clement, Emily; Kühn, Peter; Marano, Jason

doi:10.1073/pnas.0800289105

Cited by 41 publications

(54 citation statements)

References 40 publications

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“…We developed and described in detail isolation and characterization of β-EP-producing cells derived from neural stem cells (NSCs) (Sarkar et al, 2008). Briefly, NSCs were isolated from mediobasal hypothalamic tissue of 17-day old fetal Sprague-Dawley rats (Charles River).…”

Section: Methodsmentioning

confidence: 99%

β‐Endorphin Neuronal Transplantation Into the Hypothalamus Alters Anxiety‐Like Behaviors in Prenatal Alcohol‐Exposed Rats and Alcohol‐Non‐Preferring and Alcohol‐Preferring Rats

Logan

Wynne

Maglakelidze

et al. 2015

Alcoholism Clin & Exp Res

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Background Alcohol exposure has adverse effects on stress physiology and behavioral reactivity. This is suggested to be due, in part, to the effect of alcohol on β-endorphin (β-EP) producing neurons in the hypothalamus. In response to stress, β-EP normally provides negative feedback to the HPA axis and interacts with other neurotransmitter systems in the amygdala to regulate behavior. We examined whether β-EP neuronal function in the hypothalamus reduces the corticosterone response to acute stress, attenuates anxiety-like behaviors, and modulates alcohol drinking in rats. Methods To determine if β-EP neuronal transplants modulate the stress response, anxiety behavior and alcohol drinking, we implanted differentiated β-EP neurons into the paraventricular nucleus of the hypothalamus (PVN) of normal, prenatal alcohol exposed, and alcohol-preferring (P) and non-preferring (NP) rats. We then assessed corticosterone levels in response to acute restraint stress and other markers of stress response in the brain, and anxiety-like behaviors in the elevated plus maze and open-field assays. Results We showed that β-EP neuronal transplants into the PVN reduced the peripheral corticosterone response to acute stress and attenuated anxiety-like behaviors. Similar transplants completely reduced the hyper-corticosterone response and elevated anxiety behaviors in prenatal alcohol exposed adult rats. Moreover, we showed that β-EP reduced anxiety behavior in P rats with minimal effects on alcohol drinking during and following restraint stress. Conclusions These data further establish a role of β-EP neurons in the hypothalamus for regulating physiological stress response and anxiety behavior, and resembles a potential novel therapy for treating stress-related psychiatric disorders in prenatal alcohol exposed children and those genetically predisposed to increased alcohol consumption.

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Section: Methodsmentioning

confidence: 99%

β‐Endorphin Neuronal Transplantation Into the Hypothalamus Alters Anxiety‐Like Behaviors in Prenatal Alcohol‐Exposed Rats and Alcohol‐Non‐Preferring and Alcohol‐Preferring Rats

Logan

Wynne

Maglakelidze

et al. 2015

Alcoholism Clin & Exp Res

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“…2A, a vs a). PACAP contributes to neuronal stem cell proliferation [24], energy balance [25], and differentiation [26,27]. Cell growth of PRNCs was not affected by PACAP-27/38 (Fig.…”

Section: Discussionmentioning

confidence: 99%

Pituitary Adenylate Cyclase Activating Polypeptide Elicits Neuroprotection Against Acute Ischemic Neuronal Cell Death Associated with NMDA Receptors

Kaneko

Tuazon

et al. 2018

Cell Physiol Biochem

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Background/Aims: The endogenous neurotrophic peptides pituitary adenylate cyclase-activating polypeptides (PACAP-27/38) protect against stroke, but the molecular mechanism remains unknown. Methods: Primary rat neural cells were exposed to PACAP-27 or PACAP-38 before induction of experimental acute ischemic stroke via oxygen-glucose deprivation-reperfusion (OGD/R) injury. To reveal PACAP’s role in neuroprotection, we employed fluorescent live/dead cell viability and caspase 3 assays, optical densitometry of mitochondrial dehydrogenase and cell growth, glutathione disulfide luciferase activity, ELISA for high mobility group box1 extracellular concentration, ATP bioluminescence, Western blot analysis of PACAP, NMDA subunits, apoptosis regulator Bcl-2, social interaction hormone oxytocin, and trophic factor BDNF, and immunocytochemical analysis of PACAP. Results: Both PACAP-27 and PACAP-38 (PACAP-27/38) increased cell viability, decreased oxidative stress-induced cell damage, maintained mitochondrial activity, prevented the release of high mobility group box1, and reduced cytochrome c/caspase 3-induced apoptosis. PACAP-27/38 increased the protein expression levels of BDNF, Bcl-2, oxytocin, and precursor PACAP. N-methyl-D-aspartate receptor (NMDAR)-induced excitotoxicity contributes to the cell death associated with stroke. PACAP-27/38 modulated the protein expression levels of NMDAR subunits. PACAP-27/38 increased the protein expression levels of the GluN1 subunit, and decreased that of the GluN2B and GluN2D subunits. PACAP-27, but not PACAP-38, increased the expression level of the GluN2C subunit. Conclusion: This study provides evidence that PACAP regulated NMDAR subunits, affording neuroprotection after OGD/R injury.

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“…Endogenous opioid peptides, such as endorphin, which is involved in body stress controlling mechanisms, have been shown recently to enhance immune function and prevent cancer growth and progression in various animal models of cancers (Boyadjieva et al 2009;Sarkar et al 2008Sarkar et al , 2011Zhang and Sarkar 2012;Sarkar and Zhang 2013;Murugan et al 2014;Zhang et al 2015). Therefore, targeting the endogenous opioid peptides receptors in the regulation of cancer chemoprevention may offer new promise for the design of therapeutic strategies.…”

Section: Introductionmentioning

confidence: 99%

A combined opiate agonist and antagonist treatment reduces prolactin secreting pituitary tumor growth

Maglakelidze

Wynne

Sarkar

2017

J. Cell Commun. Signal.

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Prolactin secreting pituitary adenomas (prolactinomas) is the most common pituitary tumors in humans. Animal studies have identified aggressive prolactinoma development in fetal alcohol exposed rats. We have recently identified a combination treatment of a μ opioid receptor antagonist naltrexone and a δ opioid receptor agonist D-Ala2-,N-Me-Phe4,Gly-ol Enkephalin (DPDPE) increases innate immune function. In this study, we tested whether naltrexone and DPDPE combination therapy is useful to control pituitary tumor growth. Fetal alcohol exposed and control Fischer 344 female rats at 60 days of age were ovariectomized and received an estrogen implant to induce prolactinomas. Six weeks after the estrogen implant, these animals received treatments of naltrexone and DPDPE or saline. The growth of the pituitary tumor prior to and after opioidergic agent treatments was visualized using magnetic resonance imaging (MRI). At the end of the treatment, pituitary weights, plasma prolactin and splenic levels of cytotoxic factors were determined. Both imaging data and weight data indicated that the volume and the weight of the pituitary were increased more after estrogen treatment in animals exposed to fetal alcohol than control. Naltrexone and DPDPE treatment reduced the weight and volume of the pituitary gland and plasma levels of prolactin in both fetal alcohol exposed and control-fed animals. The treatment of opioidergic agents also increased the levels of cytotoxic factors in the spleen. These data provide a novel possibility in treating pituitary tumors using a combination therapy of naltrexone and DPDPE.

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Cyclic adenosine monophosphate differentiated β-endorphin neurons promote immune function and prevent prostate cancer growth

Cited by 41 publications

References 40 publications

β‐Endorphin Neuronal Transplantation Into the Hypothalamus Alters Anxiety‐Like Behaviors in Prenatal Alcohol‐Exposed Rats and Alcohol‐Non‐Preferring and Alcohol‐Preferring Rats

β‐Endorphin Neuronal Transplantation Into the Hypothalamus Alters Anxiety‐Like Behaviors in Prenatal Alcohol‐Exposed Rats and Alcohol‐Non‐Preferring and Alcohol‐Preferring Rats

Pituitary Adenylate Cyclase Activating Polypeptide Elicits Neuroprotection Against Acute Ischemic Neuronal Cell Death Associated with NMDA Receptors

A combined opiate agonist and antagonist treatment reduces prolactin secreting pituitary tumor growth

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