The Emerging Role of Brain Mitochondria in Fear and Anxiety

Chioino, Alessandro; Sandi, Carmen

doi:10.1007/7854_2024_537

Alessandro Chioino^1,2 &
Carmen Sandi^1,2

Part of the book series: Current Topics in Behavioral Neurosciences

16 Altmetric

Abstract

The functional complexity of brain circuits underlies the broad spectrum of behaviors, cognitive functions, and their associated disorders. Mitochondria, traditionally known for their role in cellular energy metabolism, are increasingly recognized as central to brain function and behavior. This review examines how mitochondria are pivotal in linking cellular energy processes with the functioning of neural circuits that govern fear and anxiety. Following an introductory section in which we summarize current knowledge about fear and anxiety neural circuits, we provide a brief summary of mitochondria fundamental roles (e.g., from energy production and calcium buffering to their involvement in reactive oxygen species (ROS) generation, mitochondrial dynamics, and signaling), particularly emphasizing their contribution to synaptic plasticity, neurodevelopment, and stress response mechanisms. The review’s core focuses on the current state of knowledge regarding how mitochondrial function and dysfunction impact the neural substrates of fear and anxiety. Furthermore, we explore the implications of mitochondrial alterations in the context of posttraumatic stress disorder (PTSD) and anxiety disorders, underscoring the potential of mitochondrial pathways as new therapeutic targets. Integrating insights from genetic, biochemical, neurobiological, behavioral, and clinical studies, we propose a model in which mitochondrial function is critical for regulating the neural circuits that underpin fear and anxiety behaviors, highlighting how mitochondrial dysfunction can lead to their pathological manifestations. This integration emphasizes the potential for developing novel treatments targeting the biological roots of fear, anxiety, and related disorders. By merging mitochondrial biology with behavioral and circuit neuroscience, we enrich our neurobiological understanding of fear and anxiety, uncovering promising avenues for therapeutic intervention.

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Laboratory of Behavioral Genetics, Brain Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
Alessandro Chioino & Carmen Sandi
Synapsy Center for Neuroscience and Mental Health Research, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
Alessandro Chioino & Carmen Sandi

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Chioino, A., Sandi, C. (2024). The Emerging Role of Brain Mitochondria in Fear and Anxiety. In: Current Topics in Behavioral Neurosciences. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7854_2024_537

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Andreazza AC, Andersen ML, Alvarenga TA et al (2010) Impairment of the mitochondrial electron transport chain due to sleep deprivation in mice. J Psychiatr Res 44:775–780. https://doi.org/10.1016/j.jpsychires.2010.01.015
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