Transcriptional and epigenetic regulation of microglia in substance use disorders

Vilca, Samara J.; Margetts, Alexander V.; Pollock, Tate A.; Tuesta, Luis M.

doi:10.1016/j.mcn.2023.103838

Cited by 9 publications

(2 citation statements)

References 197 publications

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“…Specifically, H3K4 methylation and H3K27 acetylation, markers of active gene promoters and enhancers ( Calo and Wysocka, 2013 ), are linked to innate immune memory in macrophages ( Kaikkonen et al, 2013 ; Ostuni et al, 2013 ), and more recently in microglia ( Meleady et al, 2023 ). These histone post-translational modifications, along with other epigenetic enzymes and chromatin remodeling complexes, have implicated microglia in the progression of neurodegenerative disease and aging ( Cho et al, 2015 , Yeh and Ikezu, 2019 , Huang et al, 2023 ), as well as substance use disorders ( Schwarz et al, 2011 ; Crews et al, 2023 ; Vilca et al, 2023 ). Therefore, future studies will be needed to examine the underlying epigenetic machinery in microglia that may govern the lasting transcriptional and morphological changes effected by methamphetamine administration and during abstinence to the drug.…”

Section: Discussionmentioning

confidence: 99%

Microglia contribute to methamphetamine reinforcement and reflect persistent transcriptional and morphological adaptations to the drug

Vilca,

Margetts,

Höglund

et al. 2024

Brain, Behavior, and Immunity

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Section: Discussionmentioning

confidence: 99%

Microglia contribute to methamphetamine reinforcement and reflect persistent transcriptional and morphological adaptations to the drug

Vilca,

Margetts,

Höglund

et al. 2024

Brain, Behavior, and Immunity

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“…Specifically, H3K4 methylation and H3K27 acetylation, markers of active gene promoters and enhancers (Calo and Wysocka 2013), are linked to innate immune memory in macrophages (Kaikkonen, Spann et al 2013, Ostuni, Piccolo et al 2013), and more recently in microglia (Meleady, Towriss et al 2023). These histone post-translational modifications, along with other epigenetic enzymes and chromatin remodeling complexes, have implicated microglia in the progression of neurodegenerative disease and aging (Cho, Chen et al 2015, Yeh and Ikezu 2019, Huang, Malovic et al 2023), as well as substance use disorders (Schwarz, Hutchinson et al 2011, Crews, Coleman et al 2023, Vilca, Margetts et al 2023). Therefore, future studies will be needed to examine the underlying epigenetic machinery in microglia that may govern the lasting transcriptional and morphological changes effected by methamphetamine administration and during abstinence to the drug.…”

Section: Discussionmentioning

confidence: 99%

Microglia contribute to methamphetamine reinforcement and reflect persistent transcriptional and morphological adaptations to the drug

Vilca,

Margetts,

Fleites

et al. 2023

Preprint

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Methamphetamine use disorder (MUD) is a chronic, relapsing disease that is characterized by repeated drug use despite negative consequences and for which there are currently no FDA approved cessation therapeutics. Repeated methamphetamine (METH) use induces long-term gene expression changes in brain regions associated with reward processing and drug-seeking behavior, and recent evidence suggests that methamphetamine-induced neuroinflammation may also shape behavioral and molecular responses to the drug. Microglia, the resident immune cells in the brain, are principal drivers of neuroinflammatory responses and contribute to the pathophysiology of substance use disorders. Here, we investigated transcriptional and morphological changes in striatal microglia in response to methamphetamine-taking and during methamphetamine abstinence, as well as their functional contribution to drug-taking behavior. We show that methamphetamine self-administration induces transcriptional changes related to protein folding, mRNA processing, immune signaling, and neurotransmission in striatal microglia. Importantly, many of these transcriptional changes persist through abstinence, a finding supported by morphological analysis. Functionally, we report that microglial ablation increases methamphetamine-taking, possibly involving neuroimmune and neurotransmitter regulation. In contrast, microglial depletion did not alter methamphetamine-seeking behavior following 21 days of abstinence, highlighting the complexity of drug-seeking behaviors. Taken together, these results suggest that methamphetamine induces both short and long-term changes in striatal microglia that contribute to altered drug-taking behavior and may be leveraged for preclinical development of methamphetamine cessation therapeutics.

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Neuroscience and addiction research: current advances and perspectives

Darcq,

Kieffer

2024

J Neural Transm

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Transcriptional and epigenetic regulation of microglia in substance use disorders

Cited by 9 publications

References 197 publications

Microglia contribute to methamphetamine reinforcement and reflect persistent transcriptional and morphological adaptations to the drug

Microglia contribute to methamphetamine reinforcement and reflect persistent transcriptional and morphological adaptations to the drug

Microglia contribute to methamphetamine reinforcement and reflect persistent transcriptional and morphological adaptations to the drug

Neuroscience and addiction research: current advances and perspectives

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