Loss of SLC9A6/NHE6 impairs nociception in a mouse model of Christianson syndrome

Petitjean, Hugues; Fatima, Tarheen; Mouchbahani-Constance, Stephanie; Davidova, Albena; Ferland, Catherine; Orlowski, John; Sharif‐Naeini, Reza

doi:10.1097/j.pain.0000000000001961

Cited by 13 publications

(7 citation statements)

References 43 publications

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“…NHE6, an endosomal sodium-hydrogen exchanger known to be important in the regulation of endosomal pH, is encoded by Solute carrier family 9 member A6 (SLC9A6) ( Yamashiro et al, 1984 ; Xinhan et al, 2011 ). Defects in the SLC9A6/NHE6 transporter have been linked to changes in somatosensory functions, according to a recent study ( Sikora et al, 2016 ; Petitjean et al, 2020 ). Defects in the spinal cord, the nociceptor level, or supraspinal locations can cause sensory impairments.…”

Section: Discussionmentioning

confidence: 99%

LncRNA/miRNA/mRNA ceRNA network analysis in spinal cord injury rat with physical exercise therapy

Wang

et al. 2022

PeerJ

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Noncoding RNAs have been implicated in the pathophysiology of spinal cord injury (SCI), including cell death, glial scar formation, axonal collapse and demyelination, and inflammation. The evidence suggests that exercise therapy is just as effective as medical treatment in SCI. However, studies of competing endogenous RNA (ceRNA)-mediated regulation mechanisms in the therapy of SCI with exercise are rare. The focus of this research was to investigate the effect of exercise therapy on the expression levels of long noncoding RNA (lncRNA), microRNA (miRNA), and mRNA in rats with SCI. The RNA-seq technology has been used to examine the differentially expressed circRNAs (DECs), lncRNAs (DELs), miRNAs (DEMs), and genes (DEGs) between SCI and exercise therapy rats. The ceRNA network was established using interactions between miRNAs and mRNAs, as well as between miRNAs and lncRNAs/circRNAs. The Database for Annotation, Visualization, and Integrated Discovery was used to anticipate the underlying functions of mRNAs. Our current study identified 76 DELs, 33 DEMs, and 30 DEGs between groups of SCI rats and exercise therapy rats. Subsequently, these newly discovered ceRNA interaction axes could be important targets for the exercise treatment of SCI.

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Section: Discussionmentioning

confidence: 99%

LncRNA/miRNA/mRNA ceRNA network analysis in spinal cord injury rat with physical exercise therapy

Wang

et al. 2022

PeerJ

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“…Therefore, one can hypothesize that monoterpene will induce a desensitization of TRPM8 and TRPA1, leading to a decrease of mechanical and cold thresholds, eventually leading to analgesia. Comparable mechanism exists for the TRP vanilloid 1 (TRPV1), a channel involved in the detection of nociceptive hot temperatures and activated by the red chili pepper active compound, capsaicin 17 : plantar capsaicin injection induces in naïve animals nocifensives reactions and pain hypersensitivities 41,42 , while long exposure of capsaicin induces a long-term desensitization of the TRPV1 contributing to capsaicin-induced analgesia.…”

Section: Discussionmentioning

confidence: 99%

Anti-Inflammatory and Analgesic Properties of Pulegone, a Major Component in Calamintha Nepeta

Charlet

Petitjean²,

Hilfiger

et al. 2021

Preprint

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Monoterpenes are small molecules, composed of two isoprene units, able to pass through the blood brain barrier, allowing to target both peripheral and central pain pathways. They are the main components of essential oils, responsible for their diverse well-known biological activities. Menthol, the main monoterpene found in Mentha piperita (L.) is known to modulate nociceptive threshold and is present in different curative preparations that reduces sensory hypersensitivities in pain conditions. While pulegone is a menthol-like monoterpene, only a limited number of studies focuses on its putative analgesic effects. Pulegone is the most abundant monoterpene presents in Calamintha nepeta (L.), a Laminaceae plant used in traditional medicine to alleviate rheumatic disorders, a chronic inflammatory disease. Here, we compared the impacts of menthol and pulegone on pain and inflammation. First, we described that both monoterpenes are anti-inflammatory compounds. Secondly, we found that while menthol is highly cytotoxic at anti-inflammatory concentrations, the cytotoxic effects of pulegone are limited, if not absent. Finally, in a model of peripheral inflammatory-induced pain a pulegone treatment exerts a significantly higher anti-hyperalgesic effect than menthol in response to mechanical stimuli, heat and cold thermal stimulations than a menthol treatment. In conclusion we demonstrated that pulegone is an anti-inflammatory compound and it is acting a potent pain-killer in acute inflammatory pain condition.

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“…CS is a rare but increasingly diagnosed neurodevelopmental and degenerative form of X-linked intellectual disability disorder. NHE6 regulates recycling endosomal pH homeostasis and trafficking (Petitjean et al, 2020). The ion transporter is abundantly expressed in the central nervous system (CNS), which may explain why the neural phenotype of CS is so complex and diverse.…”

Section: Discussionmentioning

confidence: 99%

Case Report: Christianson Syndrome Caused by SLC9A6 Mutation: From Case to Genotype-Phenotype Analysis

Lan

et al. 2021

Front. Genet.

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Christianson syndrome (CS) is an X-linked neurodevelopmental syndrome characterized by microcephaly, epilepsy, ataxia, and severe generalized developmental delay. Pathogenic mutations in the SLC9A6 gene, which encodes the Na+/H+ exchanger protein member 6 (NHE6), are associated with CS and autism spectrum disorder in males. In this study, whole exome sequencing (WES) and Sanger sequencing revealed a novel de novo frameshift variant c.1548_1549insT of SLC9A6 in a 14-month-old boy with early-onset seizures. According to The American College of Medical Genetics and Genomics (ACMG)/the Association for Molecular Pathology (AMP) guidelines, the variant was classified as pathogenic. The proband presented with several core symptoms of typical epilepsy, including microcephaly, motor delay, distal muscle weakness, micrognathia, occasional unprovoked laughter, swallowing and speech difficulties. Electroencephalography (EEG) showed spikes-slow waves in frontal pole, frontal, anterior temporal and frontal midline point areas. Gesell development schedules (GDS) indicated generalized developmental delay. We also summarized all the reported variants and analyzed the correlation of genotype and phenotype of CS. Our study extends the mutation spectrum of the SLC9A6 gene, and it might imply that the phenotypes of CS are not correlated with SLC9A6 genotypes.

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Loss of SLC9A6/NHE6 impairs nociception in a mouse model of Christianson syndrome

Cited by 13 publications

References 43 publications

LncRNA/miRNA/mRNA ceRNA network analysis in spinal cord injury rat with physical exercise therapy

LncRNA/miRNA/mRNA ceRNA network analysis in spinal cord injury rat with physical exercise therapy

Anti-Inflammatory and Analgesic Properties of Pulegone, a Major Component in Calamintha Nepeta

Case Report: Christianson Syndrome Caused by SLC9A6 Mutation: From Case to Genotype-Phenotype Analysis

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