Biology subjects

Konopka, W.

Publications and source records attributed to Konopka, W..

4 recordsLinked to original sources

bioRxiv2024

Hormetic curve of dietary mono- and disaccharide content determines weight gain, gut microbiota composition and cognitive ability in mice

Hormesis is defined as dose response phenomenon characterized by low-dose stimulation and high-dose inhibition (Calabrese & Mattson, 2017). To date, low doses of several stressors (intermittent fasting, caloric restriction or selected phytochemicals) have been shown to exert beneficial effects on health (Martin et al., 2006). In the present study, we aimed to determine hormetic factors in a series of diets used in mice. We found that animals fed high-sugar diet (HSD) or high-fat diet (HFD) containing relatively high amounts of mono- and disaccharides become obese compared to animals fed standard diet (STAND) or ketogenic diet (KD) containing low doses of these compounds. Underlying the observed metabolic phenotype may be changes in the composition of the intestinal microbiota, showing u-shaped features in selected species. It is noteworthy that a short-term dietary regimen of several weeks resulted in difficulties in achieving effective scores on a complex cognitive test based on spatial procedural acquisition in the HSD and HFD groups. Our data identify dietary mono- and disaccharide content (commonly known as sugars) as a critical hormetic factor with beneficial/harmful effects at multiple levels of body function.

neuroscience↗

bioRxiv2024

Enhanced purinergic signaling in the paraventricular hypothalamus induces hyperphagic obesity and insulin resistance

Body energy homeostasis is tightly regulated by hypothalamic neural circuits. However, their remodeling upon metabolic challenges remains incompletely characterized, thus complicating the development of safe medications against the surge of metabolic diseases. Oxytocin (OXT) neurons in the paraventricular nucleus of the hypothalamus (PVH) are one of the key effectors regulating energy balance. In this work, we report that high-fat diet (HFD) feeding in mice evokes spatiotemporally selective ATP release from astrocytes (Inflares) in the PVH, accompanied by the expression of hematopoietic lineage-specific ADP/ATP receptor P2Y12 on local OXT (PVHOXT) neurons. Strikingly, increased purinergic signaling leads to impaired responsiveness of PVHOXT neurons accompanied by hyperphagic obesity and insulin resistance in mice. Conversely, loss of P2Y12 in PVHOXT neurons attenuates metabolic phenotypes, illustrating that such remodeling is both necessary and sufficient to induce metabolic phenotypes. Inflares were also induced by hyperglycemia, while emergence of P2Y12 on OXT neurons of patients with diabetes mellitus suggests an evolutionary conserved purinergic response to various metabolic challenges and its potential as a drug target. Accordingly, nasal administration of clinically approved doses of P2Y12 inhibitors counteracts obesity in mice and non-human primates, paving the way for application of these compounds in patients with metabolic disorders.

neuroscience↗

bioRxiv2020

More than a feeling: central amygdala mediates social transfer of information about proximity of danger

To survive, an animal must adequately respond to challenges presented by the environment. Social animals can learn about danger from fear of conspecifics which allows them to avoid predation and other threats without costly, first-hand experience. However, it remains unclear as to whether animals can transmit specific information that helps an individual avoid harm or whether the transmitted social signals simply increase vigilance in a non-specific manner. Here we demonstrate that animals can select appropriate defensive strategies in a novel environment depending on cues from the conspecific and, using opsins targeted to behaviorally activated neurons, identify distinct neuronal circuits in the central amygdala (CeA) that are crucial for choosing a context-appropriate reaction. The identified circuits differ in molecular markers and patterns of connectivity. Thus, we show that social signals carry explicit information about proximity of danger, necessary for choosing a context-appropriate reaction, and that the choosing process is mediated by the CeA circuits.

neuroscience↗

bioRxiv2018

Amot regulates neuronal dendritic tree through Yap1

The Amot-Yap1 complex plays a major role in the regulation of cell contact inhibition, cellular polarity and growth. However, the function of Angiomotin (Amot) and Hippo pathway transcription co-activator Yap1 in the central nervous system remains unclear. In this study, we demonstrate that Amot is a critical mediator of dendritic morphogenesis in cultured hippocampal cells and Purkinje cells in the brain. Amot function in developing hippocampal neurons depends on interactions with Yap1, which is also indispensable for dendrite growth and arborization in vitro. Conditional deletion of Amot or Yap1 in neurons leads to impaired morphogenesis of Purkinje cell dendritic trees, decreased cerebellar size, and causes defects in locomotor coordination of mutant animals. Thus, our studies identified Amot and Yap1 as novel regulators of dendritic tree morphogenesis.

neuroscience↗