Astrocytic and microglial interleukin-1β mediates complement C1q-triggered orofacial mechanical allodynia

Hong, Chaoli; Hayashi, Yoshinori; Hitomi, Suzuro; Kurisu, Ryoko; Urata, Kentaro; Shibuta, Ikuko; Toyofuku, Akira; Iwata, Koichi; Shinoda, Masamichi

doi:10.1016/j.neures.2022.10.009

Cited by 4 publications

(3 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, this effect was observed in WGA + and WGA- cells suggesting the role of Csf1/Csf1R signaling in females may not be restricted to the tongue tissue. Similar to Csf1R, the contribution of C1q proteins in pain including orofacial pain as been reported to be in microglia 70 – 72 . Therefore, the sensory neuronal role of C1q proteins in pain is entirely unexplored possibly due to the fact that most studies are conducted in males that do not express neuronal C1q.…”

Section: Discussionmentioning

confidence: 64%

Sex-dependent differences in the genomic profile of lingual sensory neurons in naïve and tongue-tumor bearing mice

Ibrahim,

Wu,

Wang

et al. 2023

Sci Rep

View full text Add to dashboard Cite

Mechanisms of sex-dependent orofacial pain are widely understudied. A significant gap in knowledge exists about comprehensive regulation of tissue-specific trigeminal sensory neurons in diseased state of both sexes. Using RNA sequencing of FACS sorted retro-labeled sensory neurons innervating tongue tissue, we determined changes in transcriptomic profiles in males and female mice under naïve as well as tongue-tumor bearing conditions Our data revealed the following interesting findings: (1) FACS sorting obtained higher number of neurons from female trigeminal ganglia (TG) compared to males; (2) Naïve female neurons innervating the tongue expressed immune cell markers such as Csf1R, C1qa and others, that weren’t expressed in males. This was validated by Immunohistochemistry. (3) Accordingly, immune cell markers such as Csf1 exclusively sensitized TRPV1 responses in female TG neurons. (4) Male neurons were more tightly regulated than female neurons upon tumor growth and very few differentially expressed genes (DEGs) overlapped between the sexes, (5) Male DEGs contained higher number of transcription factors whereas female DEGs contained higher number of enzymes, cytokines and chemokines. Collectively, this is the first study to characterize the effect of sex as well as of tongue-tumor on global gene expression, pathways and molecular function of tongue-innervating sensory neurons.

show abstract

Section: Discussionmentioning

confidence: 64%

Sex-dependent differences in the genomic profile of lingual sensory neurons in naïve and tongue-tumor bearing mice

Ibrahim,

Wu,

Wang

et al. 2023

Sci Rep

View full text Add to dashboard Cite

show abstract

“…The expression of C1QA , a key microglial gene involved in microglia activation [28, 29], was slightly but significantly downregulated in both PD and control transplanted microglia compared to in vitro differentiated microglia. Additionally, the expression of genes coding for the pro-inflammatory cytokines IL1B and TNF was significantly downregulated, and the expression of the gene coding for IL10, an anti-inflammatory cytokine, was significantly upregulated in transplanted control microglia compared to in vitro differentiated control microglia.…”

Section: Resultsmentioning

confidence: 99%

The A53T mutation in α-synuclein enhances pro-inflammatory activation in human microglia

Krzisch,

Yuan,

Chen

et al. 2023

Preprint

View full text Add to dashboard Cite

Parkinson's disease (PD) is characterized by the aggregation of alpha-synuclein into Lewy bodies and Lewy neurites in the brain. Microglia-driven neuroinflammation may contribute to neuronal death in PD, however the exact role of microglia remains unclear and has been understudied. The A53T mutation in the gene coding for alpha-synuclein has been linked to early-onset PD, and exposure to A53T-mutant human alpha-synuclein increases the potential for inflammation of murine microglia. To date, its effect has not been studied in human microglia. Here, we used 2-dimensional cultures of human iPSC-derived microglia and transplantation of these cells into the mouse brain to assess the effects of the A53T mutation on human microglia. We found that A53T-mutant human microglia had an intrinsically increased propensity towards pro-inflammatory activation upon inflammatory stimulus. Additionally, A53T mutant microglia showed a strong decrease in catalase expression in non-inflammatory conditions, and increased oxidative stress. Our results indicate that A53T mutant human microglia display cell-autonomous phenotypes that may worsen neuronal damage in early-onset PD.

show abstract

“…Csf1R in microglia and macrophages has been reported to be activated in neuropathic pain via its ligand Csf1 expressed in sensory neurons (70). Similarly, the contribution of microglia-expressed C1q proteins have also been reported in pain including orofacial pain (72)(73)(74). Additionally, it has been shown that Csf1R exerts its action in a sex-specific manner by favoring a response in males compared to females(75).…”

Section: Discussionmentioning

confidence: 99%

Sex-dependent Differences in the Genomic Profile of Lingual Sensory Neurons in Naïve and Tongue-Tumor Bearing Mice

Ibrahim

Wang

et al. 2023

Preprint

View full text Add to dashboard Cite

While sex-specific prevalence of orofacial pain is established, mechanisms of sex-dependent orofacial pain are widely understudied. To this end, a significant gap in knowledge exists about comprehensive regulation of tissue-specific trigeminal sensory neurons in diseased state of males and females. Using RNA sequencing of FACS sorted retro-labeled sensory neurons innervating tongue tissue, we determined changes in transcriptomic profiles in males and female mice under naive as well as tongue-tumor bearing conditions Our data revealed the following interesting findings: 1) Tongue tissue of female mice was innervated with higher number of trigeminal neurons compared to males; 2) Naive female neurons innervating the tongue exclusively expressed immune cell markers such as Csf1R, C1qa and others, that werent expressed in males. This was validated by Immunohistochemistry. 3) Male neurons were more tightly regulated than female neurons upon tumor growth; 4) While very few differentially expressed genes (DEGs) overlapped between males and females post-tumor growth, several biological processes (BPs) were similar between two sexes. However, additional distinct processes were sex-specific; 5) Post-tumor growth, male DEGs contained an equal mix of transcription factors, ligands, growth factors, receptors and channels, whereas female DEGs predominantly contained channels/receptors, enzymes, cytokines and chemokines. Taken together, this is the first study to characterize the effect of sex as well as of tongue-tumor on global gene expression, biological pathways and molecular function of tongue-innervating sensory neurons.

show abstract

Astrocytic and microglial interleukin-1β mediates complement C1q-triggered orofacial mechanical allodynia

Cited by 4 publications

References 38 publications

Sex-dependent differences in the genomic profile of lingual sensory neurons in naïve and tongue-tumor bearing mice

Sex-dependent differences in the genomic profile of lingual sensory neurons in naïve and tongue-tumor bearing mice

The A53T mutation in α-synuclein enhances pro-inflammatory activation in human microglia

Sex-dependent Differences in the Genomic Profile of Lingual Sensory Neurons in Naïve and Tongue-Tumor Bearing Mice

Contact Info

Product

Resources

About