Showing papers by "Tamas L. Horvath published in 2023"

Impaired Ghrelin Signaling Does Not Lead to Alterations of Anxiety-like Behaviors in Adult Mice Chronically Exposed to THC during Adolescence

Abstract: As marijuana use during adolescence has been increasing, the need to understand the effects of its long-term use becomes crucial. Previous research suggested that marijuana consumption during adolescence increases the risk of developing mental illnesses, such as schizophrenia, depression, and anxiety. Ghrelin is a peptide produced primarily in the gut and is important for feeding behavior. Recent studies have shown that ghrelin and its receptor, the growth hormone secretagogue receptor (GHSR), play important roles in mediating stress, as well as anxiety and depression-like behaviors in animal models. Here, we investigated the effects of chronic tetrahydrocannabinol (THC) administration during late adolescence (P42–55) in GHSR (GHSR −/−) knockout mice and their wild-type littermates in relation to anxiety-like behaviors. We determined that continuous THC exposure during late adolescence did not lead to any significant alterations in the anxiety-like behaviors of adult mice, regardless of genotype, following a prolonged period of no exposure (1 month). These data indicate that in the presence of intact or impaired ghrelin/GHSR signaling, THC exposure during late adolescence has limited if any long-term impact on anxiety-like behaviors in mice.

Two‐Year observational study of autonomic skin function in patients with Parkinson's disease compared to healthy individuals

Abstract: We characterized autonomic pilomotor and sudomotor skin function in early Parkinson's disease (PD) longitudinally.

Neonatal loss of FGFR2 in astroglial cells affects locomotion, sociability, working memory, and glia-neuron interactions in mice

Abstract: Abstract Fibroblast growth factor receptor 2 (FGFR2) is almost exclusively expressed in glial cells in postnatal mouse brain, but its impact in glia for brain behavioral functioning is poorly understood. We compared behavioral effects from FGFR2 loss in both neurons and astroglial cells and from FGFR2 loss in astroglial cells by using either the pluripotent progenitor-driven hGFAP-cre or the tamoxifen-inducible astrocyte-driven GFAP-creER T2 in Fgfr2 floxed mice. When FGFR2 was eliminated in embryonic pluripotent precursors or in early postnatal astroglia, mice were hyperactive, and had small changes in working memory, sociability, and anxiety-like behavior. In contrast, FGFR2 loss in astrocytes starting at 8 weeks of age resulted only in reduced anxiety-like behavior. Therefore, early postnatal loss of FGFR2 in astroglia is critical for broad behavioral dysregulation. Neurobiological assessments demonstrated that astrocyte-neuron membrane contact was reduced and glial glutamine synthetase expression increased only by early postnatal FGFR2 loss. We conclude that altered astroglial cell function dependent on FGFR2 in the early postnatal period may result in impaired synaptic development and behavioral regulation, modeling childhood behavioral deficits like attention deficit hyperactivity disorder (ADHD).

A small-molecule degrader of TET3 as treatment for anorexia nervosa in an animal model

Abstract: Significance Anorexia nervosa is a life-threatening psychiatric illness with poorly understood cellular and molecular mechanisms and limited treatment options. Emerging evidence points to the importance of hypothalamic agouti-related peptide (AgRP) neurons in anorexia nervosa, but the underlying molecular mechanisms linking AgRP neurons to this illness have remained ill-defined. Here, we show that Bobcat339, a synthetic small molecule that controls TET3 in AgRP neurons, is able to mitigate anorexia nervosa and associated anxiety/depressive behaviors in a murine model. We show that Bobcat339 acts to destabilize TET3 protein in AgRP neurons and that this regulation is conserved in human and mouse cells. We propose that Bobcat339 should be pursued as a therapeutic for anorexia nervosa and perhaps cancer-induced anorexia and associated mood disorders.

Hypothalamic thyroid hormone deficiency underlies reversible anorexia in a mammalian hibernator

Abstract: Mammalian hibernators survive prolonged periods of cold and resource scarcity by temporarily modulating normal physiological functions, but the mechanisms underlying these adaptations are poorly understood. The hibernation cycle of thirteen-lined ground squirrels lasts for 5–7 months and comprises weeks of hypometabolic, hypothermic torpor interspersed with 24–48-hour periods of an active-like interbout arousal (IBA) state. We show that ground squirrels, who endure the entire hibernation season without food, have negligible hunger drive during IBAs. These squirrels exhibit reversible inhibition of the hypothalamic feeding center, such that hypothalamic arcuate nucleus neurons exhibit reduced sensitivity to the orexigenic and anorexigenic effects of ghrelin and leptin, respectively. However, hypothalamic infusion of thyroid hormone during an IBA is sufficient to rescue hibernation anorexia. Our results reveal that thyroid hormone deficiency underlies hibernation anorexia and demonstrate the functional flexibility of the hypothalamic feeding center.

A STOP-BANG kérdőív hatékonysága a benignus horkolás és az enyhe obstruktív alvási apnoe kiszűrésében

Abstract: Bevezetés: Az alvásfüggő légzészavarok arany standard diagnosztikus eszköze a poliszomnográfia. A respiratorikus pulzoximetria alkalmazható szűrővizsgálatként, előszűrés céljából pedig számos kérdőív áll rendelkezésünkre az obstruktív alvási apnoe rizikójának felmérésére. A STOP-BANG kérdőív egyszerűen használható, és irodalmi adatok alapján jó hatásfokú. Célkitűzés: A STOP-BANG kérdőív hatékonyságának vizsgálata a benignus horkolók és az enyhe obstruktív alvási apnoe betegségben szenvedők kiszűrésére. Módszer: Retrospektív módon feldolgoztuk az osztályunkon 2021. 06. 20. és 2022. 03. 19. között alvásfüggő légzészavar gyanúja miatt vizsgált betegek adatait. Kórlapelemzés alapján utólagosan STOP-BANG-rizikót állapítottunk meg, melyet összevetettünk a respiratorikus pulzoximetria leletével. Mivel a kérdőív elemei közül egyedül a horkolás erősségét nem ismertük, az elemzést a hangos horkolás vonatkozásában pozitív és negatív eredménnyel is elvégeztük. Szenzitivitást, specificitást, pozitív, illetve negatív prediktív értékeket határoztunk meg. Eredmények: 36 beteg adatait dolgoztuk fel, 1 betegünk vizsgálata kétszer történt meg testsúlyvesztés miatt. A respiratorikus pulzoximetria 19 beteg esetében igazolt benignus horkolást, 9-nél enyhe, 4-nél középsúlyos, 5-nél súlyos obstruktív alvási apnoét. A hangos horkolás kritériumát pozitívnak feltételezve, a habituális horkoló és az enyhe obstruktív alvási apnoés betegeket egészségesnek véve, a STOP-BANG kérdőívre vonatkoztatott szenzitivitás 100%-nak, a specificitás 21%-nak, a pozitív prediktív érték 29%-nak, a negatív prediktív érték 100%-nak igazolódott. Hangos horkolást nem feltételezve, a szenzitivitás 100%-os, a specificitás 54%-os, a pozitív prediktív érték 41%-os, a negatív prediktív érték 100%-os eredményt adott. Következtetés: A STOP-BANG kérdőív hatékony, az alapellátásban is alkalmazható eszköz a benignus horkolók és az enyhe obstruktív alvási apnoés betegek kiszűrésére. Bevezetésével csökkenthetjük a felesleges eszközös vizsgálatok számát, és jelentősen lerövidíthetjük a magas rizikójú betegek várakozási idejét az alvásvizsgálatokra. Orv Hetil. 2023; 164(7): 265–272.