JAK2/STAT3 Pathway is Required for α7nAChR-Dependent Expression of POMC and AGRP Neuropeptides in Male Mice

Souza, Camilla M.; Amaral, Camilla Libardi do; Souza, Suleyma Costa; Souza, Anelise C. P.; Martins, Ísis de Cássia Alves; Contieri, Letícia S.; Milanski, Marciane; Torsoni, Adriana Souza; Ignácio-Souza, Letícia Martins; Torsoni, Márcio Alberto

doi:10.33594/000000166

Cited by 19 publications

(4 citation statements)

References 31 publications

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“…In the past few years, our group has shown that α7nAchR activation in mice hypothalamus plays an important role in regulating the expression of anorexigenic neuropeptides, resulting in the reduction of food intake [ 14 ]. However, hypothalamic expression of α7nAchR can be impaired under pro-inflammatory conditions.…”

Section: Introductionmentioning

confidence: 99%

Activation of the α7 Nicotinic Acetylcholine Receptor Prevents against Microglial-Induced Inflammation and Insulin Resistance in Hypothalamic Neuronal Cells

Amaral

Martins

Verás

et al. 2022

Cells

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Neuronal hypothalamic insulin resistance is implicated in energy balance dysregulation and contributes to the pathogenesis of several neurodegenerative diseases. Its development has been intimately associated with a neuroinflammatory process mainly orchestrated by activated microglial cells. In this regard, our study aimed to investigate a target that is highly expressed in the hypothalamus and involved in the regulation of the inflammatory process, but still poorly investigated within the context of neuronal insulin resistance: the α7 nicotinic acetylcholine receptor (α7nAchR). Herein, we show that mHypoA-2/29 neurons exposed to pro-inflammatory microglial conditioned medium (MCM) showed higher expression of the pro-inflammatory cytokines IL-6, IL-1β, and TNF-α, in addition to developing insulin resistance. Activation of α7nAchR with the selective agonist PNU-282987 prevented microglial-induced inflammation by inhibiting NF-κB nuclear translocation and increasing IL-10 and tristetraprolin (TTP) gene expression. The anti-inflammatory role of α7nAchR was also accompanied by an improvement in insulin sensitivity and lower activation of neurodegeneration-related markers, such as GSK3 and tau. In conclusion, we show that activation of α7nAchR anti-inflammatory signaling in hypothalamic neurons exerts neuroprotective effects and prevents the development of insulin resistance induced by pro-inflammatory mediators secreted by microglial cells.

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Section: Introductionmentioning

confidence: 99%

Activation of the α7 Nicotinic Acetylcholine Receptor Prevents against Microglial-Induced Inflammation and Insulin Resistance in Hypothalamic Neuronal Cells

Amaral

Martins

Verás

et al. 2022

Cells

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“…Stattic was given according to previous study (Souza et al, 2019). The cannula was connected with a polyethylene tube to a Hamilton syringe.…”

Section: Drug Administrationmentioning

confidence: 99%

Adiponectin Promotes Neurogenesis After Transient Cerebral Ischemia Through STAT3 Mediated BDNF Upregulation in Astrocytes

Wang

Xia

et al. 2022

Neurochem Res

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Newborn neurons from the subventricular zone (SVZ) are essential to functional recovery following ischemic stroke. However, most of these newly generated neurons die quickly and fail to form functional connections with surrounding neurons. Thus, methods to promote neurogenesis and the survival of newborn neurons are of signi cance to post-stroke recovery. Adiponectin could increase neurogenesis in the dentate gyrus of hippocampus in neurodegenerative diseases. Therefore, we wonder whether adiponectin could also promote neurogenesis in SVZ and improve functional recovery after ischemic stroke. In addition, the critical role of astrocyte-derived BDNF in promotion of the neurogenesis should be veri ed. Here, we adopted the middle cerebral artery occlusion model of mice, and started the adiponectin treatment on day 3 of reperfusion. Neurogenesis and brain atrophy were analyzed by morphological methods, and neurological function was assessed by the adhesive removal test and the forepaw grip strength. The levels of BDNF and p-STAT3 were detected by western blotting. The adeno associated virusencoded BDNF shRNA with GFAP promoter and a STAT3 inhibitor Stattic were used. We found that adiponectin improved neurological recovery, reduced brain atrophy, and increased both the doublecortinpositive cells and NeuN/BrdU double-positive cells. Mechanically, adiponectin increased the protein levels of p-STAT3 and BDNF in astrocytes, while silence of BDNF diminished the adiponectin-induced neurogenesis and functional recovery. Moreover, inhibition of STAT3 not only reversed the increase of BDNF but also the neurogenesis and functional recovery. Collectively, we conclude that adiponectin enhances neurogenesis and functional recovery after ischemic stroke via STAT3/BDNF pathway in astrocytes.

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“…Additionally, the association of α7 nAChR with Janus kinase 2 (JAK2) has been described, and this association leads to activation of the signal transducer and activator of transcription 3 (STAT3), resulting in a localization of STAT3 to the nucleus in neuronal mypHoA-POMC/GFP cells, where it then serves as transcription factor [ 101 ] ( Figure 1 ). However, α7 is not the only nAChR coupled to JAK2.…”

Section: Metabotropic Signaling Of Nicotinic Acetylcholine Receptorsmentioning

confidence: 99%

Nicotinic Acetylcholine Receptors in the Respiratory Tract

Hollenhorst

Krasteva‐Christ

2021

Molecules

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Nicotinic acetylcholine receptors (nAChR) are widely distributed in neuronal and non-neuronal tissues, where they play diverse physiological roles. In this review, we highlight the recent findings regarding the role of nAChR in the respiratory tract with a special focus on the involvement of nAChR in the regulation of multiple processes in health and disease. We discuss the role of nAChR in mucociliary clearance, inflammation, and infection and in airway diseases such as asthma, chronic obstructive pulmonary disease, and cancer. The subtype diversity of nAChR enables differential regulation, making them a suitable pharmaceutical target in many diseases. The stimulation of the α3β4 nAChR could be beneficial in diseases accompanied by impaired mucociliary clearance, and the anti-inflammatory effect due to an α7 nAChR stimulation could alleviate symptoms in diseases with chronic inflammation such as chronic obstructive pulmonary disease and asthma, while the inhibition of the α5 nAChR could potentially be applied in non-small cell lung cancer treatment. However, while clinical studies targeting nAChR in the airways are still lacking, we suggest that more detailed research into this topic and possible pharmaceutical applications could represent a valuable tool to alleviate the symptoms of diverse airway diseases.

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JAK2/STAT3 Pathway is Required for α7nAChR-Dependent Expression of POMC and AGRP Neuropeptides in Male Mice

Abstract: This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission.

Cited by 19 publications

References 31 publications

Activation of the α7 Nicotinic Acetylcholine Receptor Prevents against Microglial-Induced Inflammation and Insulin Resistance in Hypothalamic Neuronal Cells

Activation of the α7 Nicotinic Acetylcholine Receptor Prevents against Microglial-Induced Inflammation and Insulin Resistance in Hypothalamic Neuronal Cells

Adiponectin Promotes Neurogenesis After Transient Cerebral Ischemia Through STAT3 Mediated BDNF Upregulation in Astrocytes

Nicotinic Acetylcholine Receptors in the Respiratory Tract

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