Biology subjects

Reischl, G.

Publications and source records attributed to Reischl, G..

4 recordsLinked to original sources

bioRxiv2025

From stomach to striatum: Ghrelin infusions increase work for rewards

Preclinical evidence demonstrates that gut signals influence motivated behavior through the dopaminergic system. However, translational research in humans is scarce, and it is not known if surges of the stomach-derived hormone ghrelin acutely boost motivation via dopamine transmission. To close this gap, we investigated the effects of acyl ghrelin infusions (vs. saline) on instrumental work for rewards, brain responses, and dopamine transmission in healthy adults in a double-blind, randomized and placebo-controlled crossover study with [11C]raclopride PET-fMRI. In line with preclinical findings, ghrelin enhanced hunger sensations (p = .007), and effort for food and small rewards. Crucially, ghrelin enhanced functional connectivity between the hypothalamus and the striatum (NAcc: pSVC = .016), as well as within the striatum (NAcc<>Putamen: pSVC = .001), pointing to an enhanced coupling between homeostatic and motivational circuits. However, ghrelin did not alter dopamine binding potential (reflecting changes in endogenous tone), but boosted task-free phasic pulses of the NAcc BOLD signal (p = .020), which were negatively associated with binding potential (p = .034). During the task, ghrelin increased cue- (precentral gyrus: pFWE = .003) and effort-evoked brain responses (e.g., VTA/SN: psvc = .002) in accordance with increases in motivation. Together, these findings recapitulate preclinical work that ghrelin primarily boosts phasic dopamine release, reflecting enhanced incentive salience of food and smaller rewards. This highlights the potential of targeting gut-brain interactions to improve motivational symptoms, such as loss of appetite or anhedonia. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=131 SRC="FIGDIR/small/691596v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@4321e6org.highwire.dtl.DTLVardef@166bda5org.highwire.dtl.DTLVardef@2ca69dorg.highwire.dtl.DTLVardef@16e93a9_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2023

Active Suppression of the Nigrostriatal Pathway during Optogenetic Stimulation Revealed by Simultaneous fPET/fMRI

The dopaminergic system is a central component of the brains neurobiological framework, governing motor control, reward responses, and playing an essential role in various brain disorders such as Parkinsons disease and schizophrenia. Within this complex network, the nigrostriatal pathway represents a critical circuit for dopamine transmission from the substantia nigra to the striatum, a connection that is vital to understanding many of the disease-related dysfunctions. However, stand-alone functional magnetic resonance imaging (fMRI) is unable to study the intricate interplay between brain activation and its molecular underpinnings. In our study, the simultaneous use of [18F]FDG functional positron emission tomography (fPET)/BOLD-fMRI provided a new insight that allowed us to demonstrate an active suppression of the nigrostriatal activity during optogenetic stimulation via presynaptic autoinhibition. Our in vivo observation emphasizes that the observed BOLD signal depression during neuronal stimulation does not correlate with neuronal inactivity, but results from an active suppression of neuronal firing as shown by the high [18F]FDG signal increase. This result not only illustrates the potential of simultaneous fPET/fMRI to understand the molecular mechanisms of brain function but also provides a new perspective on how neurotransmitters such as dopamine influence hemodynamic responses in the brain.

neuroscience↗

bioRxiv2023

Western diet increases brain metabolism and adaptive immune responses in a mouse model of amyloidosis

Diet-induced body weight gain is a growing health problem worldwide, leading to several serious systemic diseases such as diabetes. Because it is often accompanied by a low-grade metabolic inflammation that alters systemic function, dietary changes may also contribute to the progression of neurodegenerative diseases. Here we demonstrate disrupted glucose and fatty acid metabolism and a disrupted plasma metabolome in a mouse model of Alzheimers disease following a western diet using a multimodal imaging approach and NMR-based metabolomics. We did not detect glial-dependent neuroinflammation, however using flow cytometry we observed T cell recruitment in the brains of western diet-fed mice. Our study highlights the role of the brain-liver-fat-axis and the adaptive immune system in the disruption of brain homeostasis due to a Western diet.

immunology↗

bioRxiv2022

Neurovascular Uncoupling: Multimodal Imaging Delineates the Acute Effects of MDMA

Psychedelic compounds have attracted increasing interest in recent years due to their therapeutic potential for psychiatric disorders. Methylenedioxymethamphetamine (MDMA) is currently being investigated in clinical trials to treat post-traumatic stress disorder. To understand the acute effects of psychedelic drugs in vivo, functional MR imaging (fMRI) has been widely used in recent years. Notably, fMRI studies have shown that MDMA leads to inhibition of brain activity, challenging earlier hypotheses indicating mainly excitatory effects. However, interpretation of hemodynamic changes induced by psychedelics is challenging because of the potent vascular effects associated with this class of substances. Therefore, this study aimed to investigate the acute effects of MDMA using simultaneous positron emission tomography (PET)/fMRI in rats. For this purpose, hemodynamic changes measured by BOLD-fMRI were related to alterations in glucose utilization and serotonin transporter (SERT) occupancy, investigated using [18F]FDG functional PET (fPET) and [11C]DASB PET. We demonstrate that MDMA induces global hemodynamic decreases accompanied by localized metabolic increases. Elevated metabolism was found primarily in limbic projection areas involved in emotion processing. Concurrent BOLD-fMRI decreases, also found in extracerebral areas, indicate that the BOLD-fMRI reductions observed in the brain are of vascular, non-neuronal origin. We further show that higher SERT occupancy strongly correlates with regional BOLD-fMRI reductions. Therefore, increased serotonin levels induced by SERT blockage may cause a neurovascular uncoupling. Correct understanding of the in vivo mechanism of MDMA not only supports ongoing research but also warrants a reassessment of previous studies on neuronal effects of psychedelics relying on neurovascular coupling.

neuroscience↗