Biology subjects

Horvath, C.

Publications and source records attributed to Horvath, C..

10 recordsLinked to original sources

bioRxiv2026

GPR180 deficiency impairs mitochondrial function and insulin secretion in pancreatic β-cells

ObjectiveG protein-coupled receptor 180 (GPR180) has been implicated in systemic energy metabolism, primarily in adipose tissue and the liver. Given impaired whole-body glucose tolerance following GPR180 dysfunction, we aimed to determine whether GPR180 regulates pancreatic {beta}-cell function. We investigated whether GPR180 contributes to {beta}-cell insulin secretion by modulating metabolic processes that couple glucose sensing to mitochondrial energy production. MethodsPhenotyping of whole-body (Gpr180 -/-) and {beta} cell-specific Gpr180 (bGpr180-KO) knockout mice was combined with gain- and loss-of-function studies in MIN6 cells. Glucose-stimulated insulin secretion, pancreatic endocrine architecture and identity, transcriptomic and metabolic profiles, as well as mitochondrial function were assessed using in vivo and in vitro approaches, including metabolic challenge tests, histology, RNA sequencing, targeted metabolomics, respirometry, and transmission electron microscopy. ResultsLoss of GPR180 impaired first-phase insulin secretion and glucose tolerance without affecting insulin sensitivity. These defects were {beta}-cell-autonomous, as confirmed in the bGpr180-KO mice and in MIN6 cells. Functional studies revealed that GPR180 regulates mitochondrial substrate utilization, anaplerotic support of the TCA cycle, and ATP generation without affecting glucose uptake or mitochondrial biogenesis. In particular, Gpr180-deficient {beta} cells showed mitochondrial membrane depolarization, reduced oxygen consumption, and endoplasmic reticulum remodeling, altering the local mitochondrial microenvironment. In vivo, Gpr180 deletion in {beta} cells led to downregulation of mitochondrial gene programs in islets, along with altered endocrine cell identity. ConclusionsGPR180 is a previously unrecognized regulator of pancreatic {beta}-cell metabolic competence and identity, linking defects in insulin secretion with alterations in mitochondrial function and endocrine cell identity. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=198 SRC="FIGDIR/small/720098v1_ufig1.gif" ALT="Figure 1"> View larger version (87K): org.highwire.dtl.DTLVardef@1f24a65org.highwire.dtl.DTLVardef@1f2371eorg.highwire.dtl.DTLVardef@10096a5org.highwire.dtl.DTLVardef@1a242be_HPS_FORMAT_FIGEXP M_FIG C_FIG

physiology↗

bioRxiv2026

Polymer-based flexible multi-shank probes for simultaneous intracortical microstimulation and two-photon calcium imaging

Intracortical microstimulation is an essential tool for basic neuroscience and sensory restoration, yet the spatiotemporal effects of advanced multielectrode stimulation strategies on cortical networks remain poorly understood. This study presents a versatile experimental platform featuring polymer-based, flexible multi-shank electrode arrays integrated with a custom high-density neurostimulator. The polyimide penetrating probes contain densely spaced iridium oxide microelectrodes on thin, flexible shanks with sharp tips designed to minimize mechanical mismatch, tissue damage, and brain dimpling. The system was validated in transgenic GCaMP6 mice through simultaneous two-photon calcium imaging and electrical stimulation in layer 2/3 of the visual cortex. Monopolar stimulation reliably evoked robust, parameter-dependent neuronal activation, with neuronal recruitment increasing as a function of current intensity and pulse duration. Bipolar stimulation produced activation patterns distinct from monopolar stimulation, with neuronal responses that were more spatially confined when bipolar electrodes were positioned in close proximity. Furthermore, static current steering--implemented by varying the current ratio between the selected electrode pair--successfully shifted the centroid of activated neuronal populations, enabling fine spatial control over the site of activation. The developed platform provides a flexible framework for investigating local neuronal responses to complex electrical stimulation paradigms, facilitating the development of neural prostheses with higher spatial precision.

neuroscience↗

bioRxiv2025

Sex Hormone Binding Globulin Controls Gender Specific Lipolytic Activity in Human Abdominal Subcutaneous Adipocytes

Regulation of lipid metabolism is fundamental for metabolic health, and adipose tissue is a central component in this process. Adipose tissue differs dramatically between women and men with a higher subcutaneous capacity for storage and healthy metabolism in women. Sex hormone-binding globulin (SHBG) contributes to the regulation of circulating sex hormone bioavailability and has been shown to predict risk of metabolic dysfunction. We here investigate the sex-specific relationship of SHBG with metabolic status and adipocyte-dependent lipolysis. We measured serum concentrations of sex hormones, SHBG, fasting glucose and insulin in a cohort of 63 women and 27 men from which adipose biopsies were collected and mature adipocytes were isolated. We found that, in women, high serum SHBG concentrations were strongly associated with low HOMA-IR in vivo, and lower baseline lipolysis but higher responsiveness to isopropanol-induced lipolysis ex vivo. In contrast, no effect of SHBG on the above-mentioned parameters were observed in men. In vitro, cultured adipocytes also increased lipolytic capacity in response to SHBG, but only in the absence of testosterone, suggesting that testosterone inhibits the catecholmine-induced lipolysis of SHBG in adipose tissue. In conclusion, we here define a novel role for SHBG in adipocyte lipolysis. At the same time, our data emphasize sex-dependent differences in adipocyte lipid metabolism, and we propose testosterone binding to SHBG as a driving factor mediating these differences.

physiology↗

bioRxiv2024

Hepatic GCGR is required for the superior weight loss effects of a structurally related analogue of the dual GCGR/GLP1R agonist survodutide

The dual glucagon/glucagon-like peptide 1 receptor (GCGR/GLP1R) agonists have superior efficacy in promoting weight loss and metabolic improvements in obesity and metabolic dysfunction-associated steatohepatitis (MASH) than current available mono-agonists. However, the mechanisms underlying these benefits are not fully understood. While the effects on appetite regulation and glucose control through GLP1R agonism are well established, the role of GCGR agonism in promoting weight loss and metabolic changes is less defined. Using a dual GCGR/GLP1R agonist BI 456908 and a selective GLP1R agonist semaglutide, we could show that the dual agonist achieved superior weight loss efficacy by engaging hepatic GCGR without adversely affecting glucose control. Furthermore, we could demonstrate that hepatic GCGR is critical for facilitating plasma and liver lipid clearance stimulated by the dual agonist. Overall, these findings highlight the crucial metabolic contributions of hepatic GCGR to the efficacy of combined GCGR/GL1R activation.

physiology↗

bioRxiv2023

DREDge: robust motion correction for high-density extracellular recordings across species

High-density microelectrode arrays (MEAs) have opened new possibilities for systems neuroscience in human and non-human animals, but brain tissue motion relative to the array poses a challenge for downstream analyses, particularly in human recordings. We introduce DREDge (Decentralized Registration of Electrophysiology Data), a robust algorithm which is well suited for the registration of noisy, nonstationary extracellular electrophysiology recordings. In addition to estimating motion from spikes in the action potential (AP) frequency band, DREDge enables automated tracking of motion at high temporal resolution in the local field potential (LFP) frequency band. In human intraoperative recordings, which often feature fast (period <1s) motion, DREDge correction in the LFP band enabled reliable recovery of evoked potentials, and significantly reduced single-unit spike shape variability and spike sorting error. Applying DREDge to recordings made during deep probe insertions in nonhuman primates demonstrated the possibility of tracking probe motion of centimeters across several brain regions while simultaneously mapping single unit electrophysiological features. DREDge reliably delivered improved motion correction in acute mouse recordings, especially in those made with an recent ultra-high density probe. We also implemented a procedure for applying DREDge to recordings made across tens of days in chronic implantations in mice, reliably yielding stable motion tracking despite changes in neural activity across experimental sessions. Together, these advances enable automated, scalable registration of electrophysiological data across multiple species, probe types, and drift cases, providing a stable foundation for downstream scientific analyses of these rich datasets.

neuroscience↗

bioRxiv2023

Propagating population activity patterns during spontaneous slow waves in the thalamus of rodents

Slow waves (SWs) represent the most prominent electrophysiological events in the thalamocortical system under anesthesia and during deep sleep. Recent studies have revealed that SWs have complex spatiotemporal dynamics and propagate across neocortical regions. However, it is still unclear whether neuronal activity in the thalamus exhibits similar propagation properties during SWs. Here, we report propagating population activity in the thalamus of ketamine/xylazine-anesthetized rats and mice visualized by high-density silicon probe recordings. In both rodent species, propagation of spontaneous thalamic activity during up-states was most frequently observed in dorsal thalamic nuclei such as the higher order posterior (Po), lateral posterior (LP) or laterodorsal (LD) nuclei. The preferred direction of thalamic activity spreading was along the dorsoventral axis, with over half of the up-states exhibiting a gradual propagation in the ventral-to-dorsal direction. Furthermore, simultaneous neocortical and thalamic recordings demonstrated that there is a weak but noticeable interrelation between propagation patterns observed during cortical up-states and those displayed by thalamic population activity. In addition, using chronically implanted silicon probes, we detected propagating activity patterns in the thalamus of naturally sleeping rats during slow-wave sleep. However, in comparison to propagating up-states observed under anesthesia, these propagating patterns were characterized by a reduced rate of occurrence and a faster propagation speed. Our findings suggest that the propagation of spontaneous population activity is an intrinsic property of the thalamocortical network during synchronized brain states such as deep sleep or anesthesia. Additionally, our data implies that the neocortex may have partial control over the formation of propagation patterns within the dorsal thalamus.

neuroscience↗

bioRxiv2023

Daily rhythms, demographics and health: findings from a nationally representative survey

The timing of daily activity in humans have been associated with various demographic and health-related factors, but the possibly complex patterns of confounding and interaction between these has not been systematically explored. We use data from Hungarostudy 2021, a nationally representative survey of 7000 Hungarians to assess the relationship between self- reported chronotype, social jetlag (using the Munich Chronotype Questionnaire), demographic variables and self-reported health and demographic variables, including ethnic and sexual minority membership. Supporting the validity of self-reports, participants with later chronotypes reported the lowest daytime sleepiness at a later clock time. We found that older age, female sex, a more eastward and southward geographical position, residence in a smaller settlement, less education and income, religiousness and cohabiting with small children were associated with an earlier chronotype. Younger age, higher education and income, and cohabiting with small children were associated with increased social jetlag. Of the 48 health-related variables surveyed, the relationship with both chronotype and social jetlag were mostly accounted for by age, sex, and socioeconomic effects, but we identified alcohol consumption, smoking, and physical activity as predictors of both social jetlag and chronotype, while a number of disorders were either positively or negatively associated with chronotype and social jetlag. Our findings from a large, nationally representative sample indicate that both biological and social factors influence chronotype and identified both demographic and health-related variables as risk factors for social jetlag. Our results, however, do not support a causal relationship between light exposure and mental health.

neuroscience↗

bioRxiv2022

Whole genome analysis sheds light on the genetic origin of Huns, Avars and conquering Hungarians

Huns, Avars and conquering Hungarians were Migration Period nomadic groups which arrived in three successive waves in the Carpathian Basin between the 5th and 9th centuries. Based on historical data each of these groups are thought to have arrived from Asia, although their exact origin and relation to other ancient and modern populations has been debated. In this study we have sequenced 9 Hun, 143 Avar and 113 Hungarian conquest period samples, and identified three core populations, representing immigrants from each period, with no recent European ancestry. Our results suggest that this "immigrant core" of both Huns and Avars originated in present day Mongolia, and their origin can be traced back to Xiongnus. On the other hand, the "immigrant core" of the conquering Hungarians derived from an earlier admixture of Mansis, early Sarmatians and descendants of late Xiongnus. In addition, we detected shared Hun-related ancestry in numerous Avar and Hungarian conquest period genetic outliers indicating a genetic link between these successive nomadic groups. Aside from the immigrant core groups we identified that the majority of the individuals from each period were local residents, harboring "native European" ancestry.

genetics↗

bioRxiv2020

A new set of composite, non-redundant electroencephalogram measures of non-rapid eye movement sleep based on the power law scaling of the Fourier spectrum

A novel method for deriving composite, non-redundant measures of non-rapid eye movement (NREM) sleep electroencephalogram (EEG) is developed on the basis of the power law scaling of the Fourier spectra. Measures derived are the spectral intercept, the slope (spectral exponent), as well as the maximal whitened spectral peak amplitude and frequency in the sleep spindle range. As a proof of concept, we apply these measures on a large sleep EEG dataset (N = 175; 81 females; age range: 17-60 years) with previously demonstrated effects of age, sex and intelligence. As predicted, aging is associated with decreased overall spectral slopes (increased exponents) and whitened spectral peak amplitudes in the spindle frequency range. In addition, age associates with decreased sleep spindle spectral peak frequencies in the frontal region. Women were characterized by higher spectral intercepts and higher spectral peak frequencies in the sleep spindle range. No sex differences in whitened spectral peak amplitudes of the sleep spindle range were found. Intelligence correlated positively with whitened spectral peak amplitudes of the spindle frequency range in women, but not in men. Last, age-related increases in spectral exponents did not differ in subjects with average and high intelligence. Our findings replicate and complete previous reports in the literature, indicating that the number of variables describing NREM sleep EEG can be effectively reduced in order to overcome redundancy and Type I statistical errors in future electrophysiological studies of sleep. Author summaryGiven the tight reciprocal relationship between sleep and wakefulness, the objective description of the complex neural activity patterns characterizing human sleep is of utmost importance in understanding the several facets of brain function, like sex differences, aging and cognitive abilities. Current approaches are either exclusively based on visual impressions expressed in graded levels of sleep depth (W, N1, N2, N3, REM), whereas computerized quantitative methods provide an almost infinite number of potential metrics, suffering from significant redundancy and arbitrariness. Our current approach relies on the assumptions that the spontaneous human brain activity as reflected by the scalp-derived electroencephalogram (EEG) are characterized by coloured noise-like properties. That is, the contribution of different frequencies to the power spectrum of the signal are best described by power law functions with negative exponents. In addition, we assume, that stages N2-N3 are further characterized by additional non-random (non-noise like, sinusoidal) activity patterns, which are emerging at specific frequencies, called sleep spindles (9-18 Hz). By relying on these assumptions we were able to effectively reduce 191 spectral measures to 4: (1) the spectral intercept reflecting the overall amplitude of the signal, (2) the spectral slope reflecting the constant ratio of low over high frequency power, (3) the frequency of the maximal sleep spindle activity and (4) the amplitude of the sleep spindle spectral peak. These 4 measures were efficient in characterizing known age-effects, sex-differences and cognitive correlates of sleep EEG. Future clinical and basic studies are supposed to be significantly empowered by the efficient data reduction provided by our approach.

neuroscience↗

bioRxiv2019

Temporary pond loss as a result of pasture abandonment: exploring the social-ecological drivers and consequences on amphibians

Amphibian conservation in farming landscapes should address two challenges. First, to understand the relationship between landuse and amphibian habitat quality and second, to understand and support of the capacity of the local communities to continue those farming practices which supports amphibian friendly habitats. While the first challenge is addressed by several studies, there is virtually no study addressing the socio-economic drivers of landuse change. The major aim of this study to fill this knowledge gap by (i) documenting the temporary pond loss in 10 years in a traditionally managed pasture as a result of land abandonment and (ii) exploring the socio-economic and environmental drivers of abandonment. The results show a dramatic increase of scrub cover in the study area as a result of land abandonment. The formation of temporary ponds was negatively influenced by the increase of scrub cover in the vicinity of ponds. There were no differences between the amphibian species assemblages nor the species richness between the lost- and persisting ponds. The social component of the research highlights possible maladaptive paths in pasture management reinforced by the village depopulation, wrong interpretation of nature protection law by officials, scrub encroachment caused decrease in pasture quality and the demotivation of locals to restart traditional grazing. Conservation efforts in traditional farming landscapes facing land abandonment should (i) target the maximization of the quality of the remaining ponds for amphibians and (ii) should support reviving traditional farming practices within the local community.

ecology↗