@article{MTMT:34566049, title = {Cholinergic control of GnRH neuron physiology and luteinizing hormone secretion in male mice: involvement of ACh/GABA co-transmission}, url = {https://m2.mtmt.hu/api/publication/34566049}, author = {Vastagh, Csaba and Farkas, Imre and Csillag, Veronika and Watanabe, Masahiko and Kalló, Imre and Liposits, Zsolt}, doi = {10.1523/JNEUROSCI.1780-23.2024}, journal-iso = {J NEUROSCI}, journal = {JOURNAL OF NEUROSCIENCE}, volume = {44}, unique-id = {34566049}, issn = {0270-6474}, abstract = {GnRH-synthesizing neurons orchestrate reproduction centrally. Early studies have proposed the contribution of acetylcholine (ACh) to hypothalamic control of reproduction, although the causal mechanisms haven't been clarified. Here, we report that in vivo pharmacogenetic activation of the cholinergic system increased the secretion of luteinizing hormone (LH) in orchidectomized mice. 3DISCO immunocytochemistry and electron microscopy revealed the innervation of GnRH neurons by cholinergic axons. Retrograde viral labeling initiated from GnRH-Cre neurons identified the medial septum and the diagonal band of Broca as exclusive sites of origin for cholinergic afferents of GnRH neurons. In acute brain slices, ACh and the ACh receptor (AChR) agonist carbachol evoked a biphasic effect on the firing rate in GnRH neurons, first increasing and then diminishing it. In the presence of tetrodotoxin, carbachol induced an inward current, followed by a decline in the frequency of mPSCs, indicating a direct influence on GnRH cells. RT-PCR and whole-cell patch-clamp studies revealed that GnRH neurons expressed both nicotinic (α4β2, α3β4, and α7) and muscarinic (M1-M5) ACh receptors. The nicotinic AChRs contributed to the nicotine-elicited inward current and the rise in firing rate. Muscarine via M1 and M3 receptors increased, while via M2 and M4 reduced the frequency of both miniature postsynaptic currents (mPSCs) and firing. Optogenetic activation of channelrhodopsin-2-tagged cholinergic axons modified GnRH neuronal activity and evoked co-transmission of ACh and GABA from a subpopulation of boutons. These findings confirm that the central cholinergic system immensely regulates GnRH neurons and activates the HPG-axis via ACh and ACh/GABA neurotransmissions in male mice.}, year = {2024}, eissn = {1529-2401}, orcid-numbers = {Vastagh, Csaba/0000-0002-5008-0999; Farkas, Imre/0000-0002-0159-4408; Liposits, Zsolt/0000-0002-3508-2750} } @article{MTMT:32600821, title = {Characterization of orexin input to dopamine neurons of the ventral tegmental area projecting to the medial prefrontal cortex and shell of nucleus accumbens}, url = {https://m2.mtmt.hu/api/publication/32600821}, author = {Kalló, Imre and Omrani, Azar and Meye, Frank J. and de Jong, Han and Liposits, Zsolt and Adan, Roger A. H.}, doi = {10.1007/s00429-021-02449-8}, journal-iso = {BRAIN STRUCT FUNC}, journal = {BRAIN STRUCTURE & FUNCTION}, volume = {227}, unique-id = {32600821}, issn = {1863-2653}, keywords = {Dopamine; prefrontal cortex; Ventral tegmental area; nucleus accumbens; orexin}, year = {2022}, eissn = {1863-2661}, pages = {1083-1098}, orcid-numbers = {Liposits, Zsolt/0000-0002-3508-2750; Adan, Roger A. H./0000-0001-8994-0661} } @article{MTMT:32110195, title = {Expression of type one cannabinoid receptor in different subpopulation of kisspeptin neurons and kisspeptin afferents to GnRH neurons in female mice}, url = {https://m2.mtmt.hu/api/publication/32110195}, author = {Wilheim, Tamás and Nagy, Krisztina and Mahendravarman Mohanraj, Mahendravarman and Ziarniak, Kamil and Watanabe, Masahiko and Sliwowska, Joanna and Kalló, Imre}, doi = {10.1007/s00429-021-02339-z}, journal-iso = {BRAIN STRUCT FUNC}, journal = {BRAIN STRUCTURE & FUNCTION}, volume = {226}, unique-id = {32110195}, issn = {1863-2653}, year = {2021}, eissn = {1863-2661}, pages = {2387-2399} } @article{MTMT:31781718, title = {Effects of Ovariectomy and Sex Hormone Replacement on Numbers of Kisspeptin-, Neurokinin B- and Dynorphin A-immunoreactive Neurons in the Arcuate Nucleus of the Hypothalamus in Obese and Diabetic Rats.}, url = {https://m2.mtmt.hu/api/publication/31781718}, author = {Ziarniak, Kamil and Kołodziejski, Paweł A and Pruszyńska-Oszmałek, Ewa and Dudek, Monika and Kalló, Imre and Sliwowska, Joanna H}, doi = {10.1016/j.neuroscience.2020.10.003}, journal-iso = {NEUROSCIENCE}, journal = {NEUROSCIENCE}, volume = {451}, unique-id = {31781718}, issn = {0306-4522}, abstract = {KNDy neurons co-expressing kisspeptin (KP), neurokinin B (NKB) and dynorphin A (DYN A) in the arcuate nucleus of the hypothalamus (ARC) are key regulators of reproduction. Their activity is influenced by metabolic and hormonal signals. Previously, we have shown that orchidectomy alters the KP-, NKB-, and DYN A-immunoreactivity in the high-fat diet-induced (HFD) obesity and diabetes type 2 (DM2) models. Considering the potential sex difference in the response of KNDy neurons, we have hypothesized that ovariectomy (OVX) and post-ovariectomy replacement with estradiol (OVX+E2) or estradiol and progesterone (OVX+E2+P4) will also affect these neurons in HFD and DM2 females. Thus, each of these treatment protocols were employed for control, HFD, and DM2 groups of rats leading to nine experimental conditions within which we have determined the number of KP-, NKB-, or DYN-immunoreactive (-ir) neurons and assessed the metabolic and hormonal profiles of the animals. Accordingly: (1) no effects of group and surgery were observed on the number of KP-ir neurons; (2) the overall number of NKB-ir neurons was higher in the OVX+E2+P4 and OVX+E2 animals compared to OVX; (3) overall, the number of DYN A-ir neurons was higher in DM2 vs. control group, and surgery had an effect on the number of DYN A-ir neurons; (4) the metabolic and hormonal profiles were altered in HFD and DM2 animals compared to controls. Current data together with our previously published results indicate sex-specific differences in the response of KNDy neurons to DM2.}, keywords = {reproduction; Diabetes; Ovariectomy; high-fat diet; KNDy neurons}, year = {2020}, eissn = {1873-7544}, pages = {184-196} } @article{MTMT:30844179, title = {Enhancement of Acoustic Microscopy Lateral Resolution: A Comparison Between Deep Learning and Two Deconvolution Methods}, url = {https://m2.mtmt.hu/api/publication/30844179}, author = {Makra, Ákos and Bost, Wolfgang and Kalló, Imre and Horváth, András and Fournelle, Marc and Gyöngy, Miklós}, doi = {10.1109/TUFFC.2019.2940003}, journal-iso = {IEEE T ULTRASON FERR}, journal = {IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL}, volume = {67}, unique-id = {30844179}, issn = {0885-3010}, year = {2020}, eissn = {1525-8955}, pages = {136-145} } @article{MTMT:30744376, title = {Blunted leptin sensitivity during hedonic overeating can be reinstated by activating galanin 2 receptors (Gal2R) in the lateral hypothalamus.}, url = {https://m2.mtmt.hu/api/publication/30744376}, author = {Leidmaa, Este and Gazea, Mary and Patchev, Alexandre V and Pissioti, Anna and Gassen, Nils Christian and Kimura, Mayumi and Liposits, Zsolt and Kalló, Imre and Almeida, Osborne F X}, doi = {10.1111/apha.13345}, journal-iso = {ACTA PHYSIOL}, journal = {ACTA PHYSIOLOGICA}, volume = {228}, unique-id = {30744376}, issn = {1748-1708}, abstract = {Since foods with high hedonic value are often consumed in excess of energetic needs, this study was designed to identify the mechanisms that may counter anorexigenic signalling in the presence of hedonic foods in lean animals.Mice, in different states of satiety (fed/fasted, or fed/fasted and treated with ghrelin or leptin, respectively), were allowed to choose between high-fat/high-sucrose and standard foods. Intake of each food type and the activity of hypothalamic neuropetidergic neurons that regulate appetite were monitored. In some cases, food choice was monitored in leptin-injected fasted mice that received microinjections of galanin receptor agonists into the lateral hypothalamus.Appetite-stimulating orexin neurons in the lateral hypothalamus are rapidly activated when lean, satiated mice consume a highly palatable food (PF); such activation (upregulated c-Fos expression) occurred even after administration of the anorexigenic hormone leptin and despite intact leptin signalling in the hypothalamus. The ability of leptin to restrain PF eating is restored when a galanin receptor 2 (Gal2R) agonist is injected into the lateral hypothalamus.Hedonically-loaded foods interrupt the inhibitory actions of leptin on orexin neurons and interfere with the homeostatic control of feeding. Overeating of palatable foods can be curtailed in lean animals by activating Gal2R in the lateral hypothalamus. This article is protected by copyright. All rights reserved.}, keywords = {GALANIN; Ghrelin; leptin; LATERAL HYPOTHALAMUS; orexin; hedonia; overeating}, year = {2020}, eissn = {1748-1716}, orcid-numbers = {Liposits, Zsolt/0000-0002-3508-2750} } @article{MTMT:30830798, title = {Hypothalamic dopamine signaling regulates brown fat thermogenesis.}, url = {https://m2.mtmt.hu/api/publication/30830798}, author = {Folgueira, Cintia and Beiroa, Daniel and Porteiro, Begoña and Duquenne, Manon and Puighermanal, Emma and Fondevila, Marcos F and Barja-Fernández, Silvia and Gallego, Rosalia and Hernández-Bautista, René and Castelao, Cecilia and Senra, Ana and Seoane, Patricia and Gómez, Noemi and Aguiar, Pablo and Guallar, Diana and Fidalgo, Miguel and Romero-Pico, Amparo and Adan, Roger and Blouet, Clemence and Labandeira-García, Jose Luís and Jeanrenaud, Françoise and Kalló, Imre and Liposits, Zsolt and Salvador, Javier and Prevot, Vincent and Dieguez, Carlos and Lopez, Miguel and Valjent, Emmanuel and Frühbeck, Gema and Seoane, Luisa M and Nogueiras, Ruben}, doi = {10.1038/s42255-019-0099-7}, journal-iso = {NAT METAB}, journal = {NATURE METABOLISM}, volume = {1}, unique-id = {30830798}, abstract = {Dopamine signaling is a crucial part of the brain reward system and can affect feeding behavior. Dopamine receptors are also expressed in the hypothalamus, which is known to control energy metabolism in peripheral tissues. Here we show that pharmacological or chemogenetic stimulation of dopamine receptor 2 (D2R) expressing cells in the lateral hypothalamic area (LHA) and the zona incerta (ZI) decreases body weight and stimulates brown fat activity in rodents in a feeding-independent manner. LHA/ZI D2R stimulation requires an intact sympathetic nervous system and orexin system to exert its action and involves inhibition of PI3K in the LHA/ZI. We further demonstrate that, as early as 3 months after onset of treatment, patients treated with the D2R agonist cabergoline experience an increase in energy expenditure that persists for one year, leading to total body weight and fat loss through a prolactin-independent mechanism. Our results may provide a mechanistic explanation for how clinically used D2R agonists act in the CNS to regulate energy balance.}, keywords = {Dopamine; DOPAMINE-RECEPTOR; PROLACTIN; cholesterol; sex hormone binding globulin; triacylglycerol; stress activated protein kinase; protein kinase B; Fibroblast growth factor 21; orexin receptor; high-density lipoprotein cholesterol; orexin receptors; low density lipoprotein-cholesterol}, year = {2019}, eissn = {2522-5812}, pages = {811-829}, orcid-numbers = {Liposits, Zsolt/0000-0002-3508-2750} } @article{MTMT:30809153, title = {MCH Regulates SIRT1/FoxO1 and Reduces POMC Neuronal Activity to Induce Hyperphagia, Adiposity and Glucose Intolerance.}, url = {https://m2.mtmt.hu/api/publication/30809153}, author = {Al-Massadi, Omar and Quiñones, Mar and Clasadonte, Jerome and Bautista, René H and Romero-Picó, Amparo and Folgueira, Cintia and Morgan, Donald A and Kalló, Imre and Heras, Violeta and Senra, Ana and Funderburk, Samuel C and Krashes, Michael J and Souto, Yara and Fidalgo, Miguel and Luquet, Serge and Chee, Melissa J and Imbernon, Monica and Beiroa, Daniel and García-Caballero, Lucía and Gallego, Rosalia and Lam, Brian Y H and Yeo, Giles and Lopez, Miguel and Liposits, Zsolt and Rahmouni, Kamal and Prevot, Vincent and Dieguez, Carlos and Nogueiras, Ruben}, doi = {10.2337/db19-0029}, journal-iso = {DIABETES}, journal = {DIABETES}, volume = {68}, unique-id = {30809153}, issn = {0012-1797}, abstract = {Melanin concentrating hormone (MCH) is an important regulator of food intake, glucose metabolism and adiposity. However, the mechanisms mediating these actions remain largely unknown. We used pharmacological and genetic approaches to show that the SIRT1/FoxO1 signaling pathway in the hypothalamic arcuate nucleus (ARC) mediates MCH-induced feeding, adiposity and glucose intolerance. MCH reduces POMC neuronal activity and the SIRT1/FoxO1 pathway regulates the inhibitory effect of MCH on POMC expression. Remarkably, the metabolic actions of MCH are compromised in mice lacking SIRT1 specifically in POMC neurons. Of note, the actions of MCH are independent of AgRP neurons because inhibition of GABA-R in the ARC did not prevent the orexigenic action of MCH; and the hypophagic effect of MCH silencing was maintained after chemogenetic stimulation of AgRP neurons. Central SIRT1 is required for MCH-induced weight gain through its actions on the sympathetic nervous system. The central MCH knockdown causes hypophagia and weight loss in diet-induced obese wild type mice, however, these effects were abolished in mice over-expressing SIRT1 fed a high fat diet. These data reveal the neuronal basis for the effects of MCH on food intake, body weight and glucose metabolism and highlight the relevance of SIRT1/FoxO1 pathway in obesity.}, year = {2019}, eissn = {1939-327X}, pages = {2210-2222}, orcid-numbers = {Liposits, Zsolt/0000-0002-3508-2750} } @article{MTMT:3348809, title = {Chronic Amyloid beta Oligomer Infusion Evokes Sustained Inflammation and Microglial Changes in the Rat Hippocampus via NLRP3.}, url = {https://m2.mtmt.hu/api/publication/3348809}, author = {Fekete, Csaba and Vastagh, Csaba and Dénes, Ádám and Hrabovszky, Erik and Nyíri, Gábor and Kalló, Imre and Liposits, Zsolt and Sárvári, Miklós}, doi = {10.1016/j.neuroscience.2018.02.046}, journal-iso = {NEUROSCIENCE}, journal = {NEUROSCIENCE}, volume = {405}, unique-id = {3348809}, issn = {0306-4522}, abstract = {Microglia are instrumental for recognition and elimination of amyloid beta1-42 oligomers (AbetaOs), but the long-term consequences of AbetaO-induced inflammatory changes in the brain are unclear. Here, we explored microglial responses and transciptome-level inflammatory signatures in the rat hippocampus after chronic AbetaO challenge. Middle-aged Long Evans rats received intracerebroventricular infusion of AbetaO or vehicle for 4weeks, followed by treatment with artificial CSF or MCC950 for the subsequent 4weeks. AbetaO infusion evoked a sustained inflammatory response including activation of NF-kappaB, triggered microglia activation and increased the expression of pattern recognition and phagocytic receptors. Abeta1-42 plaques were not detectable likely due to microglial elimination of infused oligomers. In addition, we found upregulation of neuronal inhibitory ligands and their cognate microglial receptors, while downregulation of Esr1 and Scn1a, encoding estrogen receptor alpha and voltage-gated sodium-channel Na(v)1.1, respectively, was observed. These changes were associated with impaired hippocampus-dependent spatial memory and resembled early neurological changes seen in Alzheimer's disease. To investigate the role of inflammatory actions in memory deterioration, we performed MCC950 infusion, which specifically blocks the NLRP3 inflammasome. MCC950 attenuated AbetaO-evoked microglia reactivity, restored expression of neuronal inhibitory ligands, reversed downregulation of ERalpha, and abolished memory impairments. Furthermore, MCC950 abrogated AbetaO-invoked reduction of serum IL-10. These findings provide evidence that in response to AbetaO infusion microglia change their phenotype, but the resulting inflammatory changes are sustained for at least one month after the end of AbetaO challenge. Lasting NLRP3-driven inflammatory alterations and altered hippocampal gene expression contribute to spatial memory decline.}, keywords = {hippocampus; spatial memory; microglia; Estrogen receptors; NLRP3-inflammasome; amyloid β(1–42) oligomer}, year = {2019}, eissn = {1873-7544}, pages = {35-46}, orcid-numbers = {Vastagh, Csaba/0000-0002-5008-0999; Liposits, Zsolt/0000-0002-3508-2750} } @article{MTMT:30573877, title = {High-fat diet and type 2 diabetes induced disruption of the oestrous cycle and alteration of hormonal profiles, but did not affect subpopulations of KNDy neurones in female rats}, url = {https://m2.mtmt.hu/api/publication/30573877}, author = {Ziarniak, Kamil and Kolodziejski, Pawel A. and Pruszynska-Oszmalek, Ewa and Kalló, Imre and Sliwowska, Joanna H.}, doi = {10.1111/jne.12651}, journal-iso = {J NEUROENDOCRINOL}, journal = {JOURNAL OF NEUROENDOCRINOLOGY}, volume = {30}, unique-id = {30573877}, issn = {0953-8194}, abstract = {Apart from the primary metabolic symptoms of obesity and/or diabetes, there are numerous secondary problems, including disruptions of the reproductive system. The KNDy neurones, which express kisspeptin, neurokinin B and dynorphin A and are located in the arcuate nucleus of the hypothalamus (ARC), are important regulators of reproduction. Their functions are highly influenced by metabolic and hormonal status. We have previously shown that, in male rats with experimentally-induced diabetes type 2 (but not with high-fat diet-induced obesity), there are alterations in the number of these cells. In the present study, we hypothesised that a high-fat diet (HFD) and/or diabetes type 2 (DM2) in female rats affect the oestrous cycle, hormonal profiles and the number of kisspeptin-immunoreactive, neurokinin B-immunoreactive and/or dynorphin A-immunoreactive neurones in the ARC. Rats were assigned to one of three groups: a control group fed a regular chow diet, a high-fat diet group (HFD) and a diabetic group (DM2), with both of the latter two groups receiving a high calorie diet (50% of energy from lard). The third group was additionally treated with streptozotocin to induce DM2. Their oestrous cycles was monitored and their metabolic and hormonal status were assessed. We found that HFD and DM2 female rats, despite having significant alterations in their metabolic and hormonal profiles, as well as disruptions of the oestrous cycle, showed no changes in the number of the kisspeptin-immunoreactive, neurokinin B-immunoreactive and/or dynorphin A-immunoreactive neurones in the ARC. However, slight differences in the rostrocaudal distribution of these neurones among groups were reported. In conclusion, the data from the present study, together with our previously published results in males, indicate sex differences in the response of KNDy neurones to DM2 but not to HFD conditions.}, keywords = {OBESITY; Diabetes; kisspeptin; KNDy neurones; oestrogen}, year = {2018}, eissn = {1365-2826}, orcid-numbers = {Pruszynska-Oszmalek, Ewa/0000-0002-7182-6905} }