ΔFosB Requires Galanin, but not Leptin, to Increase Bone Mass via the Hypothalamus, but both are needed to increase Energy expenditure

Idelevich, Anna; Sato, Koryu; Nagano, Kenichi; Rowe, Glenn C.; Gori, Francesca; Baron, Roland

doi:10.1002/jbmr.3741

Cited by 13 publications

(7 citation statements)

References 73 publications

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“…The GAL regulation of glucose and energy homeostasis was studied in animal models, where GAL-KO mice were glucose intolerant; data suggests that GAL might also play an inhibitory role in insulin secretion on a neuronal level [ 185 ]. In mice, an increase in metabolism and energy usage is caused by the ΔFosB over-expression mediated by hypothalamic neurons, which need GAL as the inducer [ 186 , 187 ]. In the central nervous system, GAL is co-expressed with serotonin and norepinephrine, of which both are involved in depressive disorder [ 188 ].…”

Section: Neuropeptides In Anxiety and Depressionmentioning

confidence: 99%

Anxiety and Depression: What Do We Know of Neuropeptides?

Kupcová

Danišovič

Grgac

et al. 2022

Behavioral Sciences

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In modern society, there has been a rising trend of depression and anxiety. This trend heavily impacts the population’s mental health and thus contributes significantly to morbidity and, in the worst case, to suicides. Modern medicine, with many antidepressants and anxiolytics at hand, is still unable to achieve remission in many patients. The pathophysiology of depression and anxiety is still only marginally understood, which encouraged researchers to focus on neuropeptides, as they are a vast group of signaling molecules in the nervous system. Neuropeptides are involved in the regulation of many physiological functions. Some act as neuromodulators and are often co-released with neurotransmitters that allow for reciprocal communication between the brain and the body. Most studied in the past were the antidepressant and anxiolytic effects of oxytocin, vasopressin or neuropeptide Y and S, or Substance P. However, in recent years, more and more novel neuropeptides have been added to the list, with implications for the research and development of new targets, diagnostic elements, and even therapies to treat anxiety and depressive disorders. In this review, we take a close look at all currently studied neuropeptides, their related pathways, their roles in stress adaptation, and the etiology of anxiety and depression in humans and animal models. We will focus on the latest research and information regarding these associated neuropeptides and thus picture their potential uses in the future.

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Section: Neuropeptides In Anxiety and Depressionmentioning

confidence: 99%

Anxiety and Depression: What Do We Know of Neuropeptides?

Kupcová

Danišovič

Grgac

et al. 2022

Behavioral Sciences

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“…In previous studies, elevated concentrations of GAL have been detected in the fracture callus of fractured bones (McDonald et al 2003) and demonstrated potential to facilitate bone formation associated with injury by inhibiting excess TNF-α and IL-1β production (McDonald et al 2007). GAL is also necessary for the leptin-independent bone mass–inducing effects of the transcription factor ΔFosB on bone homeostasis via hypothalamic neurons (Idelevich et al 2018; Idelevich et al 2019). Thus, GAL is a prototypical neurogenic effector molecule involved in skeletal homeostasis.…”

Section: Introductionmentioning

confidence: 99%

Successful Application of a Galanin-Coated Scaffold for Periodontal Regeneration

Lyu

Pandya

et al. 2021

J Dent Res

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The nervous system exerts finely tuned control over all aspects of the life of an organism, including pain, sensation, growth, and development. Recent developments in tissue regeneration research have increasingly turned to small molecule peptides to tailor and augment the biological response following tissue loss or injury. In the present study, we have introduced the small molecule peptide galanin (GAL) as a novel scaffold-coating agent for the healing and regeneration of craniofacial tissues. Using immunohistochemistry, we detected GAL and GAL receptors in healthy periodontal tissues and in the proximity of blood vessels, while exposure to our periodontal disease regimen resulted in a downregulation of GAL. In a 3-dimensional bioreactor culture, GAL coating of collagen scaffolds promoted cell proliferation and matrix synthesis. Following subcutaneous implantation, GAL-coated scaffolds were associated with mineralized bone-like tissue deposits, which reacted positively for alizarin red and von Kossa, and demonstrated increased expression and protein levels of RUNX2, OCN, OSX, and iBSP. In contrast, the GAL receptor antagonist galantide blocked the effect of GAL on Runx2 expression and inhibited mineralization in our subcutaneous implantation model. Moreover, GAL coating promoted periodontal regeneration and a rescue of the periodontal defect generated in our periodontitis model mice. Together, these data demonstrate the efficacy of the neuropeptide GAL as a coating material for tissue regeneration. They are also suggestive of a novel role for neurogenic signaling pathways in craniofacial and periodontal regeneration.

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“…Therefore, the extent to which neuropeptide‐producing neurons share bone regulatory functions remains to be elucidated. Previously, we showed that activator protein (AP1) antagonists are also capable of exerting strong regulation of energy metabolism and bone mass . AP1 antagonists are a family of transcription factors forming heterodimers between Jun and Fos proteins, regulating gene expression.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, mice in which ΔFosB or the artificial AP1 antagonist dominant‐negative JunD (DNJunD) are stereotactically targeted to the ventral hypothalamus (VHT) recapitulate the ENO2‐ΔFosB phenotype . Recently, using AP1 antagonism as a tool, we showed that AgRP‐expressing or POMC‐expressing neurons are capable of inducing high trabecular bone mass and high energy metabolism, a process which requires the presence in the VHT of the neuromediator galanin . Here, using the same genetic neuron targeting approach, we investigated whether AP1 antagonism in NPY‐expressing and CART‐expressing neurons also produces changes in energy homeostasis and bone mass.…”

Section: Introductionmentioning

confidence: 99%

“…Previously, we showed that activator protein (AP1) antagonists are also capable of exerting strong regulation of energy metabolism and bone mass. (4,(24)(25)(26)(27)(28)(29) AP1 antagonists are a family of transcription factors forming heterodimers between Jun and Fos proteins, regulating gene expression. ΔFosB is a naturally occurring splice isoform of FosB, which lacks the C-terminal transactivation domain, and thereby exhibits AP1 antagonistic properties.…”

Section: Introductionmentioning

confidence: 99%

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Both NPY-Expressing and CART-Expressing Neurons Increase Energy Expenditure and Trabecular Bone Mass in Response to AP1 Antagonism, But Have Opposite Effects on Bone Resorption

Idelevich

Sato

Avihai

et al. 2020

Journal of Bone and Mineral Research

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Energy metabolism and bone homeostasis share several neuronal regulatory pathways. Within the ventral hypothalamus (VHT), the orexigenic neurons co‐express Agouti‐related peptide (AgRP) and neuropeptide Y (NPY) and the anorexigenic neurons co‐express, α‐melanocyte stimulating hormone derived from proopiomelanocortin (POMC), and cocaine and amphetamine‐regulated transcript (CART). These neurons regulate both processes, yet their relative contribution is unknown. Previously, using genetically targeted activator protein (AP1) alterations as a tool, we showed in adult mice that AgRP or POMC neurons are capable of inducing whole‐body energy catabolism and bone accrual, with different effects on bone resorption. Here, we investigated whether co‐residing neurons exert similar regulatory effects. We show that AP1 antagonists targeted to NPY‐producing or CART‐producing neurons in adult mice stimulate energy expenditure, reduce body weight gain and adiposity and promote trabecular bone formation and mass, yet again via different effects on bone resorption, as measured by serum level of carboxy‐terminal collagen type I crosslinks (CTX). In addition, AP1 antagonists promote neurite expansion, increasing neurite number, length, and surface area in primary hypothalamic neuronal cultures. Overall, our data demonstrate that the orexigenic NPY and anorexigenic CART neurons both have the capacity to stimulate energy burning state and increase bone mass. © 2020 American Society for Bone and Mineral Research.

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ΔFosB Requires Galanin, but not Leptin, to Increase Bone Mass via the Hypothalamus, but both are needed to increase Energy expenditure

Cited by 13 publications

References 73 publications

Anxiety and Depression: What Do We Know of Neuropeptides?

Anxiety and Depression: What Do We Know of Neuropeptides?

Successful Application of a Galanin-Coated Scaffold for Periodontal Regeneration

Both NPY-Expressing and CART-Expressing Neurons Increase Energy Expenditure and Trabecular Bone Mass in Response to AP1 Antagonism, But Have Opposite Effects on Bone Resorption

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