Chemogenetic modulation of astrocytes and microglia: State‐of‐the‐art and implications in neuroscience

Bossuyt, Jo; Herrewegen, Yana Van Den; Nestor, Liam; Buckinx, An; Bundel, Dimitri De; Smolders, Ilse Julia

doi:10.1002/glia.24390

Cited by 14 publications

(7 citation statements)

References 321 publications

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“…While chemogenetic techniques have been extensively utilized for their ability to impact neuronal signaling (Keifer et al, 2020; Urban & Roth, 2015), this method has only recently begun to be optimized for use in non-neuronal cell types (Bossuyt et al, 2023; Dheer et al, 2024; Parusel et al, 2023). AAVs, particularly AAV1, have been determined to effectively transduce microglial cells across the brain (Aschauer et al, 2013) and the activity of these cells, along with the resulting pro-inflammatory cytokine release, have also been shown to be regulated through GPCR-mediated mechanisms (Hayashi et al, 2011; Hoffmann et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

“…AAVs, particularly AAV1, have been determined to effectively transduce microglial cells across the brain (Aschauer et al, 2013) and the activity of these cells, along with the resulting pro-inflammatory cytokine release, have also been shown to be regulated through GPCRmediated mechanisms (Hayashi et al, 2011;Hoffmann et al, 2003). Importantly, viral transduction into microglia has been observed to have regional heterogeneity (Aschauer et al, 2013;Bossuyt et al, 2023), these are the first experiments to assess the LC and observe a high level of microglial transduction within this region. Further, species specific differences in microglial genetics, primarily the ~6x higher levels of CD68 RNA observed in resting microglia from rat cells versus those from mice (Lam et al, 2017), may influence differential rates of transfection between the species.…”

Section: Discussionmentioning

confidence: 99%

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The functional role of locus coeruleus microglia in the female stress response

Smiley,

Pate,

Bouknight

et al. 2024

Preprint

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Neuropsychiatric disorders that result from stress exposure, including post-traumatic stress disorder and substance abuse, are highly associated with central inflammation. Our previous work established that females selectively exhibit increased proinflammatory cytokine release within the noradrenergic locus coeruleus (LC) in response to witnessing social stress, which was associated with a hypervigilant phenotype. Thus, neuroimmune activation in the LC may be responsible for the heightened risk of developing mental health disorders following stress in females. Further, ablation of microglia using pharmacological techniques reduces the hypervigilant behavioral response exhibited by females during social stress. Therefore, these studies were designed to further investigate the impact of stress-induced neuroimmune signaling on the long-term behavioral and neuronal consequences of social stress exposure in females using DREADDs. We first characterized the use of an AAV-CD68-Gi-DREADD virus targeted to microglia within the LC. While the use of AAVs in preclinical research has been limited by observations regarding poor transfection efficiency in mice, recent data suggest that species specific differences in microglial genetics may render rats more receptive to chemogenetic targeting of microglia using a CD68 promoter. Therefore, clozapine-n-oxide (CNO) was used to activate the microglial expressed hM4Di to inhibit microglial activity during acute exposure to vicarious social defeat (witness stress, WS) in female rats. Neuroimmune activity within the LC, quantified by microglial morphology and cytokine release, was augmented by WS and prevented by chemogenetic microglial inhibition. Following confirmation of DREADD selectivity and efficacy, we utilized this technique to inhibit microglial activity during repeated WS. Subsequently, rats were tested in a marble burying paradigm and exposed to the WS cues and context to measure hypervigilant behaviors. Chemogenetic-mediated inhibition of microglial activity prior to each WS exposure prevented both acute and long-term hypervigilant responses induced by WS across multiple behavioral paradigms. Further, a history of microglial inactivation during WS prevented the heightened LC activity typically observed in response to stress cues. These studies are among the first to use a chemogenetic approach to inhibit microglia within the female brainin vivoand establish LC inflammation as a key mechanism underlying the behavioral and neuronal responses to social stress in females.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The functional role of locus coeruleus microglia in the female stress response

Smiley,

Pate,

Bouknight

et al. 2024

Preprint

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“…This alteration of movement could generate intestinal dysbiosis [ 14 ]. Intestinal dysbiosis alters the function of the microbiota, which dysfunction alerts spinal and central glial cells, as well as astrocytes in the brain [ 15 , 16 ]. The intestine can produce different molecules (microbe-derived neurotransmitters) able to pass the various intestinal and peritoneal barriers and reach the medulla and/or the central nervous system (brain-intestine axis) [ 15 ].…”

Section: Reviewmentioning

confidence: 99%

“…The intestine can produce different molecules (microbe-derived neurotransmitters) able to pass the various intestinal and peritoneal barriers and reach the medulla and/or the central nervous system (brain-intestine axis) [ 15 ]. These neurotransmitters stimulate glial cells, astrocytes (and oligodendrocytes) to produce pro-inflammatory substances and alter myelin, disturbing the correct neural transmission, and generating a pain and inflammation loop [ 15 , 16 ]. If the pain or dysfunction is chronic there will be a structural and functional change of the nervous system [ 17 ].…”

Section: Reviewmentioning

confidence: 99%

Practice of Peritoneal Adhesions in Osteopathic Medicine: Part 2

Bordoni,

Girgenti,

Escher

2023

Cureus

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Peritoneal adhesions are an unwanted and frequent event following abdominal surgery, with a response rate that can reach 100%. The adhesions can be symptomatic, becoming a source of pain and discomfort for the patient, or asymptomatic, with possible chronic or acute visceral dysfunction. The article reviews what the diagnostic strategies are and discusses what could be the causes that lead to chronic pain in the presence of adhesions. The text reports the knowledge of the literature on the manual treatment of adhesions and illustrates possible symptoms that are not easily recognized by the clinician. To conclude, the article proposes osteopathic manual approaches derived from clinical experience and from what has been explained about the formation of peritoneal adhesions. Research must make further efforts to identify not only the causes triggering the formation of peritoneal neogenesis but also seek the most appropriate non-invasive treatments to help the patient.

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“… 5 Although the research on microglia is increasing, the majority of previous studies on the role of microglia in pain have focused solely on a critical aspect, lacking a comprehensive analysis of the field. Although some reviews provided an overview of the research trends in the field, 6 , 7 there is still a need for quantitative results. Therefore, it is crucial to conduct a bibliometric study on the function of microglia in relation to pain.…”

Section: Introductionmentioning

confidence: 99%

Global Trends and Hotspots on Microglia Associated with Pain from 2002 to 2022: A Bibliometric Analysis

Dong¹,

Li²,

Hui³

et al. 2023

JPR

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Background Researchers have made significant progress in microglia associated with pain in recent years. However, more relevant bibliometric analyses are still needed on trends and directions in this field. The aim of this study is to provide a comprehensive perspective and to predict future directions of pain-related microglia research via bibliometric tools. Methods English articles and reviews related with pain and microglia were extracted from the Web of Science core collection (WosCC) database between 2002 to 2022. Bibliometric tools such as VOSviewer, CiteSpace, and Bibliometrix R package were used to analyze publication characteristics, countries, authors, institutions, journals, research hotspots, and trend topics. Results A total of 2761 articles were included in this analysis. Research on microglia associated with pain has increased significantly over the last two decades. China (n = 1020, 36.94%) and the United States (n = 751, 27.20%) contributed the most in terms of publications and citations, respectively. Kyushu University published the most articles in this field compared to other institutions, and Professor Inoue Kazuhide (n = 54) at this university made outstanding contributions in this field. Molecular Pain (n = 113) was the journal with the most publication, while Journal of Neuroscience had the highest number of citations. According to the authors keywords analysis, the research in this area can be summarized into 7 clusters such as “microglia activation pathways”, “pain treatment research”, “mental symptoms of chronic pain”, and so on. Conclusion This study provides a comprehensive analysis of pain-related microglia research in the past two decades. We identified the countries, institutions, scholars, and journals with the highest number of publications and the most influence in the field, and the research trends identified in this paper may provide new insights for future research.

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Chemogenetic modulation of astrocytes and microglia: State‐of‐the‐art and implications in neuroscience

Cited by 14 publications

References 321 publications

The functional role of locus coeruleus microglia in the female stress response

The functional role of locus coeruleus microglia in the female stress response

Practice of Peritoneal Adhesions in Osteopathic Medicine: Part 2

Global Trends and Hotspots on Microglia Associated with Pain from 2002 to 2022: A Bibliometric Analysis

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