Astrocytic lactate dehydrogenase A regulates neuronal excitability and depressive-like behaviors through lactate homeostasis in mice

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Feb. 9, 2023

Abstract Alterations in energy metabolism are associated with depression. However, the role of glycolysis pathogenesis depression and underlying molecular mechanisms remain unexplored. Through an unbiased proteomic screen coupled biochemical verifications, we show that levels lactate dehydrogenase A (LDHA), a glycolytic enzyme catalyzes L-lactate production, reduced dorsomedial prefrontal cortex (dmPFC) stress-susceptible mice chronic social defeat stress (CSDS) model. Conditional knockout LDHA from brain promotes depressive-like behaviors both male female mice, accompanied decreased neuronal excitability dmPFC. Moreover, these phenotypes could be duplicated by knockdown dmPFC or specifically astrocytes. In contrast, overexpression reverses phenotypic changes CSDS-susceptible mice. Mechanistic studies demonstrate through monocarboxylic acid transporter 2 (MCT2) inhibiting large-conductance Ca 2+ -activated potassium (BK) channel. Together, results reveal maintaining to prevent behaviors.

Language: Английский

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Electroacupuncture improves swallowing function in a post-stroke dysphagia mouse model by activating the motor cortex inputs to the nucleus tractus solitarii through the parabrachial nuclei

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Feb. 13, 2023

Abstract As a traditional medical therapy, stimulation at the Lianquan (CV23) acupoint, located depression superior to hyoid bone, has been shown be beneficial in dysphagia. However, little is known about neurological mechanism by which this peripheral approach treats for Here, we first identified cluster of excitatory neurons layer 5 (L5) primary motor cortex (M1) that can regulate swallowing function male mice modulating mylohyoid activity. Moreover, found focal ischemia M1 mimicked post-stroke dysphagia (PSD) pathology, as indicated impaired water consumption and electromyographic responses mylohyoid. This dysfunction could rescued electroacupuncture (EA) CV23 acupoint (EA-CV23) manner dependent on contralateral L5. Furthermore, neuronal activation both parabrachial nuclei (PBN) nucleus tractus solitarii (NTS), was modulated M1, required ability EA-CV23 treatment improve PSD model mice. Together, these results uncover importance M1-PBN-NTS neural circuit driving protective effect against thus reveal potential strategy intervention.

Language: Английский

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The cognitive impact of light: illuminating ipRGC circuit mechanisms

Nature reviews. Neuroscience, Journal Year: 2024, Volume and Issue: 25(3), P. 159 - 175

Published: Jan. 26, 2024

Language: Английский

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40 Hz light flickering promotes sleep through cortical adenosine signaling

Cell Research, Journal Year: 2024, Volume and Issue: 34(3), P. 214 - 231

Published: Feb. 8, 2024

Abstract Flickering light stimulation has emerged as a promising non-invasive neuromodulation strategy to alleviate neuropsychiatric disorders. However, the lack of neurochemical underpinning hampered its therapeutic development. Here, we demonstrate that flickering triggered an immediate and sustained increase (up 3 h after flickering) in extracellular adenosine levels primary visual cortex (V1) other brain regions, function frequency intensity, with maximal effects observed at 40 Hz 4000 lux. We uncovered cortical (glutamatergic GABAergic) neurons, rather than astrocytes, cellular source, intracellular generation from AMPK-associated energy metabolism pathways (but not SAM-transmethylation or salvage purine pathways), efflux mediated by equilibrative nucleoside transporter-2 (ENT2) molecular pathway responsible for generation. Importantly, 20 80 Hz) 30 min enhanced non-rapid eye movement (non-REM) REM sleep 2–3 mice. This somnogenic effect was abolished ablation V1 superior colliculus) neurons genetic deletion gene encoding ENT2 ENT1), but recaptured chemogenetic inhibition focal infusion into dose-dependent manner. Lastly, also promoted children insomnia decreasing onset latency, increasing total time, reducing waking onset. Collectively, our findings establish ENT2-mediated signaling basis flickering-induced unravel novel treatment insomnia, condition affects 20% world population.

Language: Английский

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Modulation of glymphatic system by visual circuit activation alleviates memory impairment and apathy in a mouse model of Alzheimer’s disease

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 2, 2025

Alzheimer's disease is characterized by progressive amyloid deposition and cognitive decline, yet the pathological mechanisms treatments remain elusive. Here we report therapeutic potential of low-intensity 40 hertz blue light exposure in a 5xFAD mouse model disease. Our findings reveal that treatment prevents memory decline 4-month-old mice motivation loss 14-month-old mice, accompanied restoration glial water channel aquaporin-4 polarity, improved brain drainage efficiency, reduction hippocampal lipid accumulation. We further demonstrate beneficial effects are mediated through activation vLGN/IGL-Re visual circuit. Notably, concomitant use anti-Aβ antibody with demonstrates soluble Aβ clearance performance mice. These offer functional evidence on Aβ-related pathologies suggest its as supplementary strategy to augment efficacy antibody-based therapy. Treatments for (AD) limited. Here, authors show activates circuit boost glymphatic drainage, enhances memory, motivation, therapy AD.

Language: Английский

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Mood variation under dual regulation of circadian clock and light

Chronobiology International, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 23

Published: Jan. 22, 2025

The intricate relationship between circadian rhythms and mood is well-established. Disturbances in sleep often precede the development of disorders, such as major depressive disorder (MDD), bipolar (BD), seasonal affective (SAD). Two primary factors, intrinsic clocks light, drive natural fluctuations throughout day, mirroring patterns sleepiness wakefulness. Nearly all organisms possess that coordinate daily rhythms, with light serving environmental cue to synchronize these internal timekeepers 24-hour cycle. Additionally, directly influences states. Disruptions those caused by jet lag, shift work, or reduced daylight hours, can trigger exacerbate symptoms. complex subtle connections disruptions dysregulation suggest focusing solely on individual clock genes insufficient fully understand their etiology progression. Instead, instability may arise from systemic misalignments external cycles synchronization clocks. Here, we synthesize past research independent contributions regulation, drawing particularly insights animal studies illuminate fundamental mechanisms relevant human health.

Language: Английский

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Diversity of intrinsically photosensitive retinal ganglion cells: circuits and functions

Cellular and Molecular Life Sciences, Journal Year: 2020, Volume and Issue: 78(3), P. 889 - 907

Published: Sept. 23, 2020

Language: Английский

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Anti-depression effects of ketogenic diet are mediated via the restoration of microglial activation and neuronal excitability in the lateral habenula

Brain Behavior and Immunity, Journal Year: 2020, Volume and Issue: 88, P. 748 - 762

Published: May 12, 2020

Language: Английский

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Biological rhythms and chronotherapeutics in depression

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Journal Year: 2020, Volume and Issue: 106, P. 110158 - 110158

Published: Nov. 3, 2020

Language: Английский

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Circadian depression: A mood disorder phenotype

Neuroscience & Biobehavioral Reviews, Journal Year: 2021, Volume and Issue: 126, P. 79 - 101

Published: March 7, 2021

Language: Английский

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