Biology subjects

Enoki, R.

Publications and source records attributed to Enoki, R..

5 recordsLinked to original sources

bioRxiv2026

R-spondin 1 restores hypothalamic glucose-sensing and systemic glucose homeostasis via Wnt signaling in diet-induced obese mice

High-fat diet (HFD) feeding disrupts systemic glucose metabolism, yet the underlying neural mechanisms remain incompletely understood. Here, we demonstrate that glucose-excited (GE) neurons in the ventromedial hypothalamus (VMHGE) are essential for acute glucose regulation and that their function is compromised by HFD via structural synaptic remodeling. We found that HFD feeding suppresses canonical Wnt signaling and downregulates R-spondin 1 (RSPO1), a Wnt enhancer, in the VMH. This Wnt inhibition leads to a loss of dendritic spines and blunted glucose-sensing in VMHGE neurons. Conversely, central administration of RSPO1 restores Wnt/{beta}-catenin signaling, promotes synaptogenesis, and recovers neuronal glucose responsiveness. Consequently, RSPO1 treatment ameliorates HFD-induced glucose intolerance by enhancing peripheral glucose utilization. These findings identify the RSPO1-Wnt signaling axis as a critical regulator of VMH neuronal plasticity and metabolic homeostasis, providing a mechanistic link between diet-induced synaptic pathology and systemic metabolic dysfunction. Highlights- Glucose-excited neurons in VMH were labeled with TRAP - VMH glucose-excited neurons regulates systemic glucose metabolism - Wnt signaling regulates synaptogenesis in VMH and maintain neuronal glucose-sensitivity - R-spondin1 recovers VMH neuronal glucose sensitivity in HFD fed obese mice

neuroscience↗

bioRxiv2025

Artificial hibernation uncovers distinct synaptic engram architecture for memory retention

The memory trace at the neuronal and synaptic levels remains controversial. Stable, larger spines are thought to support memory, but the high turnover of dendritic spines and the drifting of neuronal representations following memory formation suggest alternative possibilities. To elucidate a structural trace underlying memory retention, we utilize a mouse model of artificial hibernation. During hibernation, hippocampal neurons exhibited a substantial reduction in their activity and an extensive elimination of dendritic spines and synapses. Despite these changes, their memory and associated hippocampal neuronal representations are intact after arousal. We find that a subset of spines is maintained during hibernation. These spatially clustered engram-engram synapses are exclusively protected from elimination and characterized by synaptic contacts with multi-synaptic boutons. These findings suggest that synaptic engram architecture, rather than larger spines per se, is resilient to network remodeling and underlies long-term memory retention.

neuroscience↗

bioRxiv2024

Amyloid-β-induced Alteration of Fast and Localized Calcium Elevations in Cultured Astrocytes

Alzheimers disease (AD) is a progressive neurodegenerative disorder that causes cognitive decline. Uncovering the mechanisms of neurodegeneration in the early stages is essential to establish a treatment for AD. Recent research has proposed the hypothesis that amyloid-{beta} (A{beta}) oligomers elicit an excessive glutamate release from astrocytes toward synapses through intracellular free Ca2+ ([Ca2+]i) elevations in astrocytes, finally resulting in neuronal dendritic spine loss. Under physiological conditions, astrocytic [Ca2+]i elevations range spatially from microdomains to network-wide propagation and temporally from milliseconds to tens of seconds. Astrocytic localized and fast [Ca2+]i elevations might correlate with glutamate release; however, the A{beta}-induced alteration of localized, fast astrocytic [Ca2+]i elevations remains unexplored. In this study, we quantitatively investigated the A{beta} dimers-induced changes in the spatial and temporal patterns of [Ca2+]i in a primary culture of astrocytes by two-photon excitation spinning-disk confocal microscopy. The frequency of fast [Ca2+]i elevations occurring locally in astrocytes ([≤]0.5 s, [≤]35 {micro}m2) and [Ca2+]i event occupancy relative to cell area significantly increased after exposure to A{beta} dimers. The effect of A{beta} dimers appeared dose-dependently above 500 nM, and these A{beta} dimers-induced [Ca2+]i elevations were primarily mediated by a metabotropic purinergic receptor (P2Y1 receptor) and Ca2+ release from the endoplasmic reticulum. Our findings suggest that the A{beta} dimers-induced alterations and hyperactivation of astrocytic [Ca2+]i is a candidate cellular mechanism in the early stages of AD.

neuroscience↗

bioRxiv2024

Body temperature regulates glucose metabolism and torpid

Glucose is a significant energy resource for maintaining physiological activities, including body temperature homeostasis, and glucose homeostasis is tightly regulated in mammals. Although ambient temperature tunes glucose metabolism to maintain euthermia, the significance of body temperature in metabolic regulation remains unclear owing to strict thermoregulation. Activation of Qrfp neurons in the preoptic area induced a harmless hypothermic state known as Q-neuron-induced hypothermia and hypometabolism (QIH), which is suitable for studying glucose metabolism under hypothermia. In this study, we first observed that QIH mice had hyperinsulinemia and insulin resistance. This glucose hypometabolic state was abolished by increasing the body temperature to euthermia. Moreover, QIH-mediated inappetence and locomotor inactivity were recovered in euthermia QIH mice. These results indicate that body temperature is considerably more powerful than ambient temperature in regulating glucose metabolism and behavior, and hypometabolism in QIH is secondary to hypothermia rather than modulated by Qrfp neurons. HighlightsO_LIQIH reorganizes glucose homeostasis which is unchanged by fasting. C_LIO_LIQIH mice exhibit glucose hypometabolism with hyperinsuliemia and insulin resistance. C_LIO_LIIncreased body temperature abolishes QIH-mediated hypometabolism and torpid behaviors. C_LIO_LIBody temperature is a strong factor in controlling metabolism and behavior. C_LIO_LIBody temperature-mediated glucose metabolism is reversible. C_LI

physiology↗

bioRxiv2022

Cold-induced Suspension and Resetting of Ca2+ and Transcriptional Rhythms in the Suprachiasmatic Nucleus Neurons

Mammalian circadian rhythms are coordinated by the master clock located in the hypothalamic suprachiasmatic nucleus (SCN). Under severe environmental conditions, such as during the harsh winter season for food, certain mammalian species reduce their basal metabolism and thermogenesis, thereby undergoing torpor, a controlled state of hypothermia, which naturally returns to the normothermic state. A long-lasting debate focused on whether the SCN with a temperature-compensated clock remains functional during hypothermia. However, so far, no direct and quantitative evidence has been reported of temperature sensitivity in living SCN neurons. In this study, we performed dual-color fluorescence imaging of clock gene transcriptions and intracellular Ca2+ in mouse SCN neurons, using slices at various temperatures. We demonstrated that the Bmal1 transcription and Ca2+ circadian rhythms persisted at 22{degrees}C-28{degrees}C, although the two rhythms underwent temporal dissociation at 22 {degrees}C. Notably, Ca2+, Bmal1, and Per2 rhythms were suspended at 15{degrees}C, coupled with a significant Ca2+ increase, and all rhythms were reset by rewarming to 35{degrees}C. Upon rewarming, the Ca2+ rhythm showed stable oscillations immediately, whereas the Bmal1 and Per2 rhythms took several days to reach stable oscillations and recover their phase relationship with the Ca2+ rhythm. Taken together, we concluded that SCN neurons remain functional under moderate hypothermic conditions at approximately 22{degrees}C-28{degrees}C but stop ticking time in deep hypothermia at 15{degrees}C and that the rhythms reset after deep hypothermia. These data also indicate that the stable Ca2+ oscillation precedes clock gene transcriptional rhythms in the SCN neurons.

neuroscience↗