Psychosocial experiences are associated with human brain mitochondrial biology

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(27)

Published: June 18, 2024

Psychosocial experiences affect brain health and aging trajectories, but the molecular pathways underlying these associations remain unclear. Normal function relies on energy transformation by mitochondria oxidative phosphorylation (OxPhos). Two main lines of evidence position both as targets drivers psychosocial experiences. On one hand, chronic stress exposure mood states may alter multiple aspects mitochondrial biology; other functional variations in OxPhos capacity social behavior, reactivity, mood. But are exposures subjective linked to biology human brain? By combining longitudinal antemortem assessments factors with postmortem (dorsolateral prefrontal cortex) proteomics older adults, we find that higher well-being is greater abundance machinery, whereas negative lower protein content. Combined, positive explained 18 25% variance complex I, primary biochemical entry point energizes mitochondria. Moreover, interrogating psychobiological specific neuronal nonneuronal cells single-nucleus RNA sequencing (RNA-seq) revealed strong cell-type-specific for glia opposite neurons. As a result, “mind-mitochondria” were masked bulk RNA-seq, highlighting likely underestimation true effect sizes tissues. Thus, self-reported phenotypes.

Language: Английский

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Distinct prefrontal projection activity and transcriptional state conversely orchestrate social competition and hierarchy

Neuron, Journal Year: 2023, Volume and Issue: 112(4), P. 611 - 627.e8

Published: Dec. 11, 2023

Language: Английский

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Mitochondrial dynamics and psychiatric disorders: The missing link

Neuroscience & Biobehavioral Reviews, Journal Year: 2024, Volume and Issue: 165, P. 105837 - 105837

Published: July 30, 2024

Language: Английский

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Nucleus Accumbens Corticotropin-Releasing Hormone Neurons Projecting to the Bed Nucleus of the Stria Terminalis Promote Wakefulness and Positive Affective State

Neuroscience Bulletin, Journal Year: 2024, Volume and Issue: 40(11), P. 1602 - 1620

Published: July 9, 2024

Abstract The nucleus accumbens (NAc) plays an important role in various emotional and motivational behaviors that rely on heightened wakefulness. However, the neural mechanisms underlying relationship between arousal emotion regulation NAc remain unclear. Here, we investigated roles of a specific subset inhibitory corticotropin-releasing hormone neurons (NAc CRH ) regulating mice. We found increased activity during wakefulness rewarding stimulation. Activation converts NREM or REM sleep to wakefulness, while inhibition these attenuates Remarkably, activation induces place preference response (PPR) decreased basal anxiety level, whereas their inactivation aversion anxious state. are identified as major projection bed stria terminalis (BNST). Furthermore, -BNST pathway similarly induced positive behaviors. Taken together, forebrain promotes associated with affective states.

Language: Английский

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A platform to map the mind–mitochondria connection and the hallmarks of psychobiology: the MiSBIE study

Trends in Endocrinology and Metabolism, Journal Year: 2024, Volume and Issue: 35(10), P. 884 - 901

Published: Oct. 1, 2024

Language: Английский

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Cannabidiol abrogates cue-induced anxiety associated with normalization of mitochondria-specific transcripts and linoleic acid in the nucleus accumbens shell

Molecular Psychiatry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 15, 2025

Language: Английский

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Mitochondrial control of ciliary gene expression and structure in striatal neurons

The Journal of Physiology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 18, 2025

Abstract Mitochondria play essential metabolic roles and are increasingly understood to interact with other organelles, influencing cellular function disease. Primary cilia, as sensory signalling crucial for neuronal communication function. Emerging evidence suggests that mitochondria primary cilia may regulate processes, recently shown in brain cells such astrocytes. Here, we investigated whether also neurons, focusing on molecular pathways linking both organelles structural components within cilia. We employed a cross‐species, pathway‐focused approach explore connections between mitochondrial ciliary revealing strong associations suggesting coordinated functionality. Furthermore, found viral‐induced downregulation of the fusion gene mitofusin 2 ( Mfn2 ) dopamine D1 receptor‐expressing medium spiny neurons (D1‐MSNs) nucleus accumbens (NAc) altered expression, Crocc – encoding rootletin showing most pronounced downregulation. This reduction expression was linked decreased levels protein, key component rootlet. Notably, viral‐mediated overexpression restored complexity elongation, without compromising adaptation Our findings provide novel functional mitochondria–cilia interaction specifically striatal D1‐MSNs. These results reveal previously unrecognized role dynamics regulating structure potential implications neuropsychiatric neurodegenerative disease mechanisms. image Key points cell structures known producing energy but emerging regulators components, including antenna‐like involved communication. Previous studies suggest influence function, However, this has not been explored neurons. study shows natural variation correlates rats mice. Reducing (Mfn2), protein mitochondria–endoplasmic reticulum interactions, changes specific pathways, notably Crocc, structure, reduces its product, rootletin, which supports integrity. an important highlighting pathway regulation signalling.

Language: Английский

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Hippocampal Pyk2 regulates specific social skills: Implications for schizophrenia

Neurobiology of Disease, Journal Year: 2024, Volume and Issue: 194, P. 106487 - 106487

Published: March 27, 2024

Pyk2 has been shown previously to be involved in several psychological and cognitive alterations related stress, Huntington's disease, Alzheimer's disease. All these disorders are accompanied by different types of impairments sociability, which recently linked improper mitochondrial function. We hypothesize that Pyk2, regulates mitochondria, could associated with the regulation dynamics social skills. In present manuscript, we report a reduction levels mouse pyramidal neurons hippocampus decreased dominance aggressivity. Furthermore, interactions induced robust Pyk2-dependent hippocampal changes oxidative phosphorylation complexes. also observed were increased CA1 schizophrenic subjects, occurring alongside direct indirect regulators function including DISC1 Grp75. Accordingly, overexpressing cells mimicked some specific schizophrenia-like behaviors mice. summary, our results indicate might play role regulating skills likely via there link between disturbances schizophrenia.

Language: Английский

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The Emerging Role of Brain Mitochondria in Fear and Anxiety

Current topics in behavioral neurosciences, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

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Psychosocial experiences are associated with human brain mitochondrial biology

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 6, 2023

Abstract Psychosocial experiences affect brain health and aging trajectories, but the molecular pathways underlying these associations remain unclear. Normal function relies heavily on energy transformation by mitochondria oxidative phosphorylation (OxPhos), two main lines of evidence bi-directionally link as both targets drivers psychosocial experiences. On one hand, chronic stress exposure possibly mood states alter multiple aspects mitochondrial biology; other functional variations in OxPhos capacity social behavior, reactivity, mood. However, knowledge whether positive or negative exposures are linked to biology human is currently unknown. By combining longitudinal antemortem assessments factors with postmortem (dorsolateral prefrontal cortex) proteomics older adults, we found that (e.g. higher well-being) greater abundance machinery, whereas mood) lower protein content. Combined, explained 18% variance complex I, primary biochemical entry point energizes mitochondria. To increase sensitivity our approach, next interrogated psychobiological specific neuronal non-neuronal cells single-nucleus RNA sequencing. These results revealed strong cell type associations, particularly between phenotypes glial cells, neurons tended show opposite associations. Accordingly, bulk transcriptomic analyses where all pooled, RNA-based were masked. Thus, highlight likely underestimation effect sizes tissues, document novel brain. Cell recalibrations represent a potential pathway linking biology. Significance statement predict mechanism remains We abundance. Overall, explain I proteins, (OxPhos) system. At single-cell resolution using single nucleus transcriptomics, related phenotypes. Opposite naturally masked analyses. Our suggest types may health.

Language: Английский

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