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Investigating the Role of Astrocyte-Neuron Lactate Shuttling in the Anterior Cingulate Cortex in Mouse Models of Inflammatory Pain

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Title: Investigating the Role of Astrocyte-Neuron Lactate Shuttling in the Anterior Cingulate Cortex in Mouse Models of Inflammatory Pain
Author: Tang, James
Department: Department of Biomedical Sciences
Program: Biomedical Sciences
Advisor: Descalzi, Giannina
Abstract: Chronic pain is one of the most prevalent debilitating conditions, affecting an estimated 1 in 5 Canadians. Despite the current treatment options, many who suffer from the condition report inadequate pain management, demonstrating a need to improve our understanding of the molecular and cellular processes underlying the condition such that new therapies can be developed. Synaptic plasticity within the central nervous system has been repeatedly implicated in the functional changes to pain-associated neural networks in chronic pain. Increasing evidence shows that astrocytes contribute to synaptic plasticity and are also involved in the pathogenesis of chronic pain. The astrocyte-neuron lactate shuttle (ANLS), where astrocytes export lactate that neurons can take up and use for energy metabolism, plays a critical role in hippocampal synaptic plasticity and in animal models of long-term memory. This thesis investigated the possible contribution of the ANLS to pain-associated synaptic plasticity in the anterior cingulate cortex (ACC), an area of the brain associated with pain and emotion, and consistently shows altered activity in both clinical populations as well as in animal models of chronic pain. Following induction of chronic hindpaw inflammation, our results indicate the development of hypersensitive pain-like behavior and a temporal pattern of increased lactate levels in the ACC. Additionally, our preliminary findings suggest that inhibiting neuronal lactate uptake via monocarboxylate transporter 2 genetic knockdown may inhibit the expression of inflammation-induced pain-like behavior.
URI: https://hdl.handle.net/10214/26472
Date: 2021-08
Rights: Attribution 4.0 International
Related Publications: Tang, J., Bair, M., and Descalzi, G. (2021). Reactive Astrocytes: Critical Players in the Development of Chronic Pain. Frontiers in Psychiatry. 12. 809. https://doi.org/10.3389/fpsyt.2021.682056


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Attribution 4.0 International Except where otherwise noted, this item's license is described as Attribution 4.0 International