Controlled activation of cortical astrocytes modulates neuropathic pain-like behaviour

Takeda, Ikuko; Yoshihara, Kohei; Cheung, Dennis Lawrence; Kobayashi, Tomoko; Agetsuma, Masakazu; Tsuda, Makoto; Eto, Kojiro; Koizumi, Schuichi; Nabekura, Junichi

doi:10.1038/s41467-022-31773-8

Cited by 24 publications

(13 citation statements)

References 56 publications

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“…Immunofluorescent staining was performed as reported previously (Takeda et al, 2022; Xu et al, 2019). Briefly, mice were perfused with ice-cold 0.9% normal saline, followed by perfusion with ice-code 4% paraformaldehyde.…”

Section: Methods Detailsmentioning

confidence: 99%

A molecularly distinct cell type in the midbrain regulates intermale aggression behaviors in mice

Li,

Miao,

et al. 2023

Preprint

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The periaqueductal gray (PAG) has been suggested as a central hub for defensive responses to threatening stimuli and regulation of aggression. However, little is known on the circuitry and molecular mechanisms that govern this regulation. Here, we investigate the role of a molecularly distinct cell type, Taschykinin 2-expressing neurons (Tac2+), located in dorsomedial PAG (dmPAG), in modulating aggression in a mouse resident-intruder model. Using a rabies-assisted input mapping strategy, we found that dmPAGTac2 neurons received monosynaptic input from the ventromedial hypothalamus, a region implicated in mediating fighting behaviors. Whole-brain Fos mapping and in vivo Ca2+ recording in mice revealed that dmPAGTac2 neurons were exclusively activated by fighting behaviors. Further, we manipulated activity of dmPAGTac2 neurons using chemogenetic tools and found that activation of dmPAGTac2 neurons evoked, while inhibition or genetic ablation of dmPAGTac2 neurons suppressed fighting behaviors. To further reveal molecular pathways that govern this fighting behaviors, we profiled dmPAGTac2 neurons using a viral-based translating ribosome affinity purification (TRAP) approach and revealed that fighting behaviors specifically induced enrichment of serotonin-associated transcripts in dmPAGTac2 neurons. Last, we validated these findings by selectively delivering pharmacological agents into the dmPAG through guide cannula and reversed the behavioral outcomes induced by chemogenetic manipulation of dmPAGTac2 neurons. Collectively, we identify that dmPAGTac2 neuron as a molecularly distinct cell type that regulate mouse aggressive behavior in dmPAG region and thus suggest a novel molecular target for the treatment of exacerbated aggressive behaviors in populations that exhibit high-level of violence.

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Section: Methods Detailsmentioning

confidence: 99%

A molecularly distinct cell type in the midbrain regulates intermale aggression behaviors in mice

Li,

Miao,

et al. 2023

Preprint

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“…DRG neurons project to the spinal cord through the dorsal horn ipsilateral to them, where they synapse with spinal neurons which ultimately relay sensory signals to the brain. The role of astrocytes in neuropathic pain is far from restricted to the spinal cord: impressive work has linked astrocytes in the cortex [ 17 , 18 , 19 , 20 , 21 ], periaqueductal gray, [ 22 , 23 ], and thalamus [ 24 ] to pain. Whether this activity is primary to or a consequence of chronic pain is a complex question beyond the purview of this review, which will focus solely on spinal astrocytes.…”

Section: Sgcs and Astrocytes In Homeostasismentioning

confidence: 99%

The Similar and Distinct Roles of Satellite Glial Cells and Spinal Astrocytes in Neuropathic Pain

McGinnis

2023

Cells

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Preclinical studies have identified glial cells as pivotal players in the genesis and maintenance of neuropathic pain after nerve injury associated with diabetes, chemotherapy, major surgeries, and virus infections. Satellite glial cells (SGCs) in the dorsal root and trigeminal ganglia of the peripheral nervous system (PNS) and astrocytes in the central nervous system (CNS) express similar molecular markers and are protective under physiological conditions. They also serve similar functions in the genesis and maintenance of neuropathic pain, downregulating some of their homeostatic functions and driving pro-inflammatory neuro-glial interactions in the PNS and CNS, i.e., “gliopathy”. However, the role of SGCs in neuropathic pain is not simply as “peripheral astrocytes”. We delineate how these peripheral and central glia participate in neuropathic pain by producing different mediators, engaging different parts of neurons, and becoming active at different stages following nerve injury. Finally, we highlight the recent findings that SGCs are enriched with proteins related to fatty acid metabolism and signaling such as Apo-E, FABP7, and LPAR1. Targeting SGCs and astrocytes may lead to novel therapeutics for the treatment of neuropathic pain.

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“…DRG neurons project to the spinal cord through the dorsal horn ipsilateral to them, where they synapse with spinal neurons which ultimately relay sensory signals to the brain. The role of astrocytes in neuropathic pain is far from restricted to the spinal cord: impressive work has linked astrocytes in cortex (17,18,19,20,21), periaqueductal gray, (22,23), and thalamus (24) to pain. Whether this activity is primary to, or a consequence of, chronic pain is a complex question beyond the prevue of this review, which will focus solely on spinal astrocytes.…”

Section: Locationmentioning

confidence: 99%

The Similar and Distinct Roles of Satellite Glial Cells and Astrocytes in Neuropathic Pain

McGinnis¹,

Ji²

2023

Preprint

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Preclinical studies have identified glial cells as pivotal players in the genesis and maintenance of neuropathic pain after nerve injury associated with diabetes, chemotherapy, major surgeries, and virus infections. Satellite glial cells (SGCs) in the dorsal root and trigeminal ganglia of the peripheral nervous system (PNS) and astrocytes in the central nervous system (CNS) express similar molecular markers and are protective under physiological conditions. They also serve similar functions in the genesis and maintenance of neuropathic pain, downregulating some of their homeostatic functions and driving pro-inflammatory neuro-glial interactions in the PNS and CNS, i.e. “gliopathy”. However, the role of SGCs in neuropathic pain is not simply as “peripheral astrocytes”. We delineate how these peripheral and central glia participate in neuropathic pain by producing different mediators, engaging different parts of neurons, and becoming active at different stages following nerve injury. Finally, we highlight the recent findings that SGCs are enriched with proteins related to fatty acid metabolism and signaling such as Apo-E, FABP7, and LPAR1. Targeting SGCs and astrocytes may lead to novel therapeutics for the treatment of neuropathic pain.

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Controlled activation of cortical astrocytes modulates neuropathic pain-like behaviour

Cited by 24 publications

References 56 publications

A molecularly distinct cell type in the midbrain regulates intermale aggression behaviors in mice

A molecularly distinct cell type in the midbrain regulates intermale aggression behaviors in mice

The Similar and Distinct Roles of Satellite Glial Cells and Spinal Astrocytes in Neuropathic Pain

The Similar and Distinct Roles of Satellite Glial Cells and Astrocytes in Neuropathic Pain

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