Journal of Neuroendocrinology最新文献

{"title":"High fat diet-induced maternal obesity in mice impairs peripartum maternal behaviour","authors":"Rosemary Shanon Eileen Brown,&nbsp;Ireland M. Jacobs,&nbsp;Zin Khant Aung,&nbsp;Pene J. Knowles,&nbsp;David R. Grattan,&nbsp;Sharon R. Ladyman","doi":"10.1111/jne.13350","DOIUrl":"10.1111/jne.13350","url":null,"abstract":"<p>Obesity during pregnancy represents a significant health issue and can lead to increased complications during pregnancy and impairments with breastfeeding, along with long-term negative health consequences for both mother and offspring. In rodent models, diet-induced obesity (DIO) during pregnancy leads to poor outcomes for offspring. Using a DIO mouse model, consisting of feeding mice a high fat diet for 8 weeks before mating, we recapitulate the effect of high pup mortality within the first 3 days postpartum. To examine the activity of the dam around the time of birth, late pregnant control and DIO dams were recorded in their home cages and the behaviour of the dam immediately before and after birth was analysed. Prior to giving birth, DIO dams spent less time engaging in nesting behaviour, while after birth, DIO dams spent less time in the nest with their pups compared to control dams, indicating reduced pup-engagement in the early postpartum period. We have previously reported that lactogenic hormone action, mediated by the prolactin receptor, in the medial preoptic area of the hypothalamus (MPOA) is critical for the onset of normal postpartum maternal behaviour. We hypothesized that DIO dams may have lower lactogenic hormone activity during late pregnancy, which would contribute to impaired onset of normal postpartum maternal behaviour. Day 16 lactogenic activity, transport of prolactin into the brain, and plasma prolactin concentrations around birth were all similar in control and DIO dams. Moreover, endogenous pSTAT5, a marker of prolactin receptor activity, in the MPOA was unaffected by DIO. Overall, these data indicate that lactogenic activity in late pregnancy of DIO dams is not different to controls and is unlikely to play a major role in impaired onset of normal postpartum maternal behaviour.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.13350","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71482609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic work-up and surgical management of insulinoma: A retrospective analysis from a tertiary referral center","authors":"Valentina Andreasi,&nbsp;Stefano Partelli,&nbsp;Francesca Muffatti,&nbsp;Anna Battistella,&nbsp;Francesca Fermi,&nbsp;Gianpaolo Balzano,&nbsp;Stefano Crippa,&nbsp;Domenico Tamburrino,&nbsp;Nicolò Pecorelli,&nbsp;Francesco De Cobelli,&nbsp;Paolo Giorgio Arcidiacono,&nbsp;Massimo Falconi","doi":"10.1111/jne.13353","DOIUrl":"10.1111/jne.13353","url":null,"abstract":"<p>Insulinoma is a multifaceted disease that poses several challenges in terms of clinical presentation, diagnostic work-up, and surgical management. The aim of this study was to describe diagnostic work-up, surgical management, and postoperative outcomes of patients with insulinoma. All consecutive patients who underwent surgery for insulinoma at San Raffaele Hospital (Milan, Italy) between January 2008 and January 2022 were included. Overall, 98 patients were considered. The median delay between presenting symptoms and insulinoma diagnosis was 10 months (IQR, 4–21). Insulinoma diagnosis was made at our Institution in 45 patients, 20 of whom referred within 6 months from symptoms onset. In this subgroup, the median interval between symptoms presentation and insulinoma diagnosis was 4 months (IQR, 2–6), as compared to 14 months (IQR, 10–26) in patients (<i>n</i> = 25) who referred to our institution after 6 months from symptoms onset (<i>p</i> &lt; .001). The insulinoma was localized preoperatively in all the cases. All patients underwent ≥1 high-quality imaging: computed tomography (CT: <i>n</i> = 87, sensitivity 84%), magnetic resonance imaging (MRI: <i>n</i> = 55, sensitivity 85%) and endoscopic ultrasound (EUS: <i>n</i> = 79, sensitivity 100%). MRI identified the tumor in eight patients with negative CT. EUS localized the insulinoma in three patients with negative CT and negative MRI. Parenchyma-sparing resections were performed in 41 patients. Contact with major vessels, lesion close to Wirsung duct and suspect of malignancy were the main reasons to perform a formal resection. An early referral to high-volume centers is important for reducing diagnostic delay in patients with insulinoma. The diagnostic work-up of insulinoma frequently requires several imaging modalities to be performed, with EUS being the most sensitive one. Parenchyma-sparing surgery for insulinoma should be performed whenever technically and oncologically feasible.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71424351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual action of serotonin on local excitatory and inhibitory neural circuits regulating the corticotropin-releasing factor neurons in the paraventricular nucleus of the hypothalamus","authors":"Takayuki Sato,&nbsp;Takuma Sugaya,&nbsp;Ashraf Hossain Talukder,&nbsp;Yuki Tsushima,&nbsp;Shotaro Sasaki,&nbsp;Katsuya Uchida,&nbsp;Tatsuya Sato,&nbsp;Yoko Ikoma,&nbsp;Kenji Sakimura,&nbsp;Atsuo Fukuda,&nbsp;Ko Matsui,&nbsp;Keiichi Itoi","doi":"10.1111/jne.13351","DOIUrl":"10.1111/jne.13351","url":null,"abstract":"<p>Serotonergic neurons originating from the raphe nuclei have been proposed to regulate corticotropin-releasing factor (CRF) neurons in the paraventricular nucleus of the hypothalamus (PVH). Since glutamate- and γ-aminobutyric acid (GABA)-containing neurons, constituting the hypothalamic local circuits, innervate PVH CRF neurons, we examined whether they mediate the actions of serotonin (5-hydroxytryptamine [5-HT]) on CRF neurons. Spontaneous excitatory postsynaptic currents (sEPSCs) or spontaneous inhibitory postsynaptic currents (sIPSCs) were recorded in PVH CRF neurons, under whole cell patch-clamp, using the <i>CRF-modified yellow fluorescent protein</i> (<i>Venus</i>) <i>ΔNeo</i> mouse. Serotonin elicited an increase in the frequency of sEPSCs in 77% of the cells and a decrease in the frequency of sIPSCs in 71% of the cells, tested in normal medium. Neither the amplitude nor decay time of sEPSC and sIPSC was affected, thus the site(s) of action of serotonin may be presynaptic. In the presence of tetrodotoxin (TTX), serotonin had no significant effects on either parameter of sEPSC or sIPSC, indicating that the effects of serotonin are action potential-dependent, and that the presynaptic interneurons are largely intact within the slice; distant neurons may exist, though, since some 20%–30% of neurons did not respond to serotonin without TTX. We next examined through what receptor subtype(s) serotonin exerts its effects on presynaptic interneurons. DOI (5-HT_2A/2C agonist) mimicked the action of serotonin on the sIPSCs, and the serotonin-induced decrease in sIPSC frequency was inhibited by a selective 5-HT_2C antagonist RS102221. 8-OH-DPAT (5-HT_1A/7 agonist) mimicked the action of serotonin on the sEPSCs, and the serotonin-induced increase in sEPSC frequency was inhibited by a selective 5-HT₇ antagonist SB269970. Thus, serotonin showed a dual action on PVH CRF neurons, by upregulating glutamatergic- and downregulating GABAergic interneurons; the former may partly be mediated by 5-HT₇ receptors, whereas the latter by 5-HT_2C receptors. The <i>CRF-Venus ΔNeo</i> mouse was useful for the electrophysiological examination.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71412604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduction of body weight by increased loading is associated with activation of norepinephrine neurones in the medial nucleus of the solitary tract","authors":"Jovana Zlatkovic,&nbsp;Adrià Dalmau Gasull,&nbsp;Daniel Hägg,&nbsp;Ferran Font-Gironès,&nbsp;Jakob Bellman,&nbsp;Björn Meister,&nbsp;Vilborg Palsdottir,&nbsp;Johan Ruud,&nbsp;Claes Ohlsson,&nbsp;Suzanne L. Dickson,&nbsp;Fredrik Anesten,&nbsp;John-Olov Jansson","doi":"10.1111/jne.13352","DOIUrl":"10.1111/jne.13352","url":null,"abstract":"<p>We previously provided evidence supporting the existence of a novel leptin-independent body weight homeostat (“the gravitostat”) that senses body weight and then initiates a homeostatic feed-back regulation of body weight. We, herein, hypothesize that this feed-back regulation involves a CNS mechanism. To identify populations of neurones of importance for the putative feed-back signal induced by increased loading, high-fat diet-fed rats or mice were implanted intraperitoneally or subcutaneously with capsules weighing ∼15% (Load) or ∼2.5% (Control) of body weight. At 3–5 days after implantation, neuronal activation was assessed in different parts of the brain/brainstem by immunohistochemical detection of FosB. Implantation of weighted capsules, both subcutaneous and intraperitoneal, induced FosB in specific neurones in the medial nucleus of the solitary tract (mNTS), known to integrate information about the metabolic status of the body. These neurones also expressed tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DbH), a pattern typical of norepinephrine neurones. In functional studies, we specifically ablated norepinephrine neurones in mNTS, which attenuated the feed-back regulation of increased load on body weight and food intake. In conclusion, increased load appears to reduce body weight and food intake via activation of norepinephrine neurones in the mNTS.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.13352","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54229572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and efficacy of peptide receptor radionuclide therapy in patients with advanced pheochromocytoma and paraganglioma: A single-institution experience and review of the literature","authors":"Charlene Yu Lin Tang,&nbsp;Wei Ming Chua,&nbsp;Hian Liang Huang,&nbsp;Winnie Wing-Chuen Lam,&nbsp;Lih Ming Loh,&nbsp;David Tai,&nbsp;Simon Yew Kuang Ong,&nbsp;Sean Xuexian Yan,&nbsp;Kelvin S. H. Loke,&nbsp;David Chee-Eng Ng,&nbsp;Wei Ying Tham","doi":"10.1111/jne.13349","DOIUrl":"10.1111/jne.13349","url":null,"abstract":"<p>Introduction: Despite advances in diagnosis and management, patients with advanced pheochromocytomas and paragangliomas (PPGL) face limited treatment options. This study aims to evaluate the safety and efficacy of peptide receptor radionuclide therapy (PRRT) in patients with advanced PPGL, based on a single-institution experience and provide a comprehensive review of the literature. Methods: A retrospective analysis was conducted on patients with advanced pheochromocytoma and paraganglioma who received PRRT at a single institution from April 2012 to March 2022. Clinical characteristics, treatment response, adverse events, and survival outcomes were assessed. A systematic literature review was also performed. Results: A total of 15 patients with advanced PPGL were included, the majority of whom had both metastatic and functional disease. Most patients received four infusions of 177Lu-DOTATATE (73%). The median therapeutic 177Lu-DOTATATE radioactivity for each infusion was 7.4 GBq. Only one patient was treated with one infusion of 90Y-DOTATATE (4.2 GBq) in addition to three infusions of Lu-177 DOTATATE. Overall, PRRT suggests a promising efficacy with disease control rate of 63.6% by RECIST v1.1. The median overall survival (OS) was not reached and the median progression free survival (PFS) was 25.9 months. In terms of safety, PRRT was well tolerated. Review of the literature revealed consistent findings, supporting the efficacy and safety of PRRT in PPGL. Conclusion: This study suggests that PRRT is a safe and effective therapeutic option for patients with PPGL. Our findings align with the existing literature, providing additional evidence to support the use of PRRT in this challenging patient population.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71482610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of maternal hormones in regulating autonomic functions during pregnancy","authors":"T. Georgescu","doi":"10.1111/jne.13348","DOIUrl":"10.1111/jne.13348","url":null,"abstract":"<p>Offspring development relies on numerous physiological changes that occur in a mother's body, with hormones driving many of these adaptations. Amongst these, the physiological functions controlled by the autonomic nervous system are required for the mother to survive and are adjusted to meet the demands of the growing foetus and to ensure a successful birth. The hormones oestrogen, progesterone, and lactogenic hormones rise significantly during pregnancy, suggesting they may also play a role in regulating the maternal adaptations linked to autonomic nervous system functions, including respiratory, cardiovascular, and thermoregulatory functions. Indeed, expression of pregnancy hormone receptors spans multiple brain regions known to regulate these physiological functions. This review examines how respiratory, cardiovascular, and thermoregulatory functions are controlled by these pregnancy hormones by focusing on their action on central nervous system circuits. Inadequate adaptations in these systems during pregnancy can give rise to several pregnancy complications, highlighting the importance in understanding the mechanistic underpinnings of these changes and potentially identifying ways to treat pregnancy-associated afflictions using hormones.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.13348","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71482611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"European Neuroendocrine Tumour Society (ENETS) 2023 guidance paper for nonfunctioning pancreatic neuroendocrine tumours","authors":"Beata Kos-Kudła,&nbsp;Justo P. Castaño,&nbsp;Timm Denecke,&nbsp;Enrique Grande,&nbsp;Andreas Kjaer,&nbsp;Anna Koumarianou,&nbsp;Louis de Mestier,&nbsp;Stefano Partelli,&nbsp;Aurel Perren,&nbsp;Stefan Stättner,&nbsp;Juan W. Valle,&nbsp;Nicola Fazio","doi":"10.1111/jne.13343","DOIUrl":"10.1111/jne.13343","url":null,"abstract":"<p>This ENETS guidance paper for well-differentiated nonfunctioning pancreatic neuroendocrine tumours (NF-Pan-NET) has been developed by a multidisciplinary working group, and provides up-to-date and practical advice on the management of these tumours. Using the extensive experience of centres treating patients with NF-Pan-NEN, the authors of this guidance paper discuss 10 troublesome questions in everyday clinical practice. Our many years of experience in this field are still being verified in the light of the results of new clinical, which set new ways of proceeding in NEN. The treatment of NF-Pan-NEN still requires a decision of a multidisciplinary team of specialists in the field of neuroendocrine neoplasms.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.13343","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50158167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic effects of atypical antipsychotics: Molecular targets","authors":"Maria Fonseca,&nbsp;Francisca Carmo,&nbsp;Fátima Martel","doi":"10.1111/jne.13347","DOIUrl":"10.1111/jne.13347","url":null,"abstract":"<p>Atypical antipsychotics (AAPs) are commonly prescribed drugs in the treatment of schizophrenia, bipolar disorder and other mental diseases with psychotic traits. Although the use of AAPs is associated with beneficial effects in these patients, they are also associated with undesired metabolic side effects, including metabolic syndrome (MetS). MeS is defined by the presence of metabolic abnormalities such as large waist circumference, dyslipidemia, fasting hyperglycemia and elevated blood pressure, which predispose to type 2 diabetes (T2D) and cardiovascular disease. In this review, the molecular and cellular mechanisms involved in these undesired metabolic abnormalities induced by AAPs are described. These mechanisms are complex as AAPs have multiple cellular targets which significantly affect the activities of several hormones and neuromodulators. Additionally, AAPs affect all the relevant metabolic organs, namely the liver, pancreas, adipose tissue, skeletal muscle and intestine, and the central and peripheral nervous system as well. A better understanding of the molecular targets linking AAPs with MetS and of the mechanisms responsible for clinically different side effects of distinct AAPs is needed. This knowledge will help in the development of novel AAPs with less adverse effects as well as of adjuvant therapies to patients receiving AAPs.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49690979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early life stress lastingly alters the function and AMPA-receptor composition of glutamatergic synapses in the hippocampus of male mice","authors":"Niek Brosens,&nbsp;Carla Simon,&nbsp;Helmut W. Kessels,&nbsp;Paul J. Lucassen,&nbsp;Harm J. Krugers","doi":"10.1111/jne.13346","DOIUrl":"10.1111/jne.13346","url":null,"abstract":"<p>Early postnatal life is a sensitive period of development that shapes brain structure and function later in life. Exposure to stress during this critical time window can alter brain development and may enhance the susceptibility to psychopathology and neurodegenerative disorders later in life. The developmental effects of early life stress (ELS) on synaptic function are not fully understood, but could provide mechanistic insights into how ELS modifies later brain function and disease risk. We here assessed the effects of ELS on synaptic function and composition in the hippocampus of male mice. Mice were subjected to ELS by housing dams and pups with limited bedding and nesting material from postnatal days (P) 2–9. Synaptic strength was measured in terms of miniature excitatory postsynaptic currents (mEPSCs) in the hippocampal dentate gyrus at three different developmental stages: the early postnatal phase (P9), preadolescence (P21, at weaning) and adulthood at 3 months of age (3MO). Hippocampal synaptosome fractions were isolated from P9 and 3MO tissue and analyzed for protein content to assess postsynaptic composition. Finally, dendritic spine density was assessed in the DG at 3MO. At P9, ELS increased mEPSC frequency and amplitude. In parallel, synaptic composition was altered as PSD-95, GluA3 and GluN2B content were significantly decreased. The increased mEPSC frequency was sustained up to 3MO, at which age, GluA3 content was significantly increased. No differences were found in dendritic spine density. These findings highlight how ELS affects the development of hippocampal synapses, which could provide valuable insight into mechanisms how ELS alters brain function later in life.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71412613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serotonergic neurons are involved in the counter-regulatory response to hypoglycemia","authors":"Hugo Martin,&nbsp;Adeline Coursan,&nbsp;Justine Lallement,&nbsp;Mathieu Di Miceli,&nbsp;Janany Kandiah,&nbsp;Ilyès Raho,&nbsp;Jasmine Buttler,&nbsp;Jean-Philippe Guilloux,&nbsp;Philippe De Deurwaerdere,&nbsp;Sophie Layé,&nbsp;Vanessa H. Routh,&nbsp;Bruno P. Guiard,&nbsp;Christophe Magnan,&nbsp;Céline Cruciani-Guglielmacci,&nbsp;Xavier Fioramonti","doi":"10.1111/jne.13344","DOIUrl":"10.1111/jne.13344","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Intensive insulin therapy provides optimal glycemic control in patients with diabetes. However, intensive insulin therapy causes so-called iatrogenic hypoglycemia as a major adverse effect. The ventromedial hypothalamus (VMH) has been described as the primary brain area initiating the counter-regulatory response (CRR). Nevertheless, the VMH receives projections from other brain areas which could participate in the regulation of the CRR. In particular, studies suggest a potential role of the serotonin (5-HT) network. Thus, the objective of this study was to determine the contribution of 5-HT neurons in CRR control.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Complementary approaches have been used to test this hypothesis in quantifying the level of 5-HT in several brain areas by HPLC in response to insulin-induced hypoglycemia, measuring the electrical activity of dorsal raphe (DR) 5-HT neurons in response to insulin or decreased glucose level by patch-clamp electrophysiology; and measuring the CRR hormone glucagon as an index of the CRR to the modulation of the activity of 5-HT neurons using pharmacological or pharmacogenetic approaches.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>HPLC measurements show that the 5HIAA/5HT ratio is increased in several brain regions including the VMH in response to insulin-induced hypoglycemia. Patch-clamp electrophysiological recordings show that insulin, but not decreased glucose level, increases the firing frequency of DR 5-HT neurons in the DR. In vivo, both the pharmacological inhibition of 5-HT neurons by intraperitoneal injection of the 5-HT1A receptor agonist 8-OH-DPAT or the chemogenetic inhibition of these neurons reduce glucagon secretion, suggesting an impaired CRR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Taken together, these data highlight a new neuronal network involved in the regulation of the CRR. In particular, this study shows that DR 5-HT neurons detect iatrogenic hypoglycemia in response to the increased insulin level and may play an important role in the regulation of CRR.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49678539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}