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This study was to observe the changes in the expression of calcium homeostasis modulator 1 in trigeminal nucleus of trigeminal neuralgia rats with the infraorbital nerve-chronic constrictive nerve injury and to explore the role of calcium homeostasis modulator 1 in trigeminal neuralgia. Thirty Sprague Dawley rats were randomly assigned to 5 groups, control group, sham group, infraorbital nerve-chronic constrictive nerve injury group, ruthenium red group and normal saline group, with 6 rats in each group. All experimental rats were tested for pain behaviour 1 d before surgery, 1, 3, 5, 7, 9, 11 and 14 d after surgery, including the mechanical pain threshold of Von Frey filament in the trigeminal innervated skin area and number of faces captured in video recording. The expression of calcium homeostasis modulator 1 in the trigeminal spinal nucleus was detected on d 15 after surgery in all experimental groups. The expression of calcium homeostasis modulator 1 in the trigeminal spinal nucleus of the infraorbital nerve-chronic constrictive nerve injury group was significantly higher than that of the control and the sham group on the 3rd and 15th d after modelling. Intraperitoneal injection of ruthenium red, a calcium homeostasis modulator 1 inhibitor, increased the mechanical pain threshold of infraorbital nerve-chronic constrictive nerve injury rats and significantly reduced the number of scratches, but did not change the expression of calcium homeostasis modulator 1 in the trigeminal spinal nucleus. In conclusion, the expression of calcium homeostasis modulator 1 protein in the trigeminal spinal nucleus is involved in the central sensitization of trigeminal neuralgia pain. Moreover, the hyperalgesia can be improved by using calcium homeostasis modulator 1 inhibitor without affecting the calcium homeostasis modulator 1 expression. [ABSTRACT FROM AUTHOR]

ATP release from urinary bladder is vital for afferent signaling. The aims of this study were to localize calcium homeostasis modulator 1 (CALHM1) and pannexin-1 expression and to determine their involvement in mediating ATP release in the bladder. To determine gene expression and cellular distribution, PCR and immunohistochemistry were performed, respectively, in the porcine bladder. CALHM1 and pannexin-1-mediated ATP release in response to hypotonic solution (0.45% NaCl)-induced stretch, and extracellular Ca2+ depletion ([Ca2+]0) was measured in isolated urothelial, suburothelial, and detrusor muscle cells. CALHM1 and pannexin-1 mRNA and immunoreactivity were detected in urothelial, suburothelial, and detrusor muscle layers, with the highest expression on urothelium. Hypotonic stretch caused a 2.7-fold rise in ATP release from all three cell populations (P < 0.01), which was significantly attenuated by the pannexin-1 inhibitor, 10Panx1, and by the CALHM1 antibody. Brefeldin A, a vesicular transport inhibitor, and ruthenium red, a nonselective CALHM1 channel blocker, also significantly inhibited stretch-mediated ATP release from urothelial cells. [Ca2+]0 caused a marked, but transient, elevation of extracellular ATP level in all three cell populations. CALHM1 antibody and ruthenium red inhibited [Ca2+]0-induced ATP release from urothelial cells, but their effects on suburothelial and detrusor cells were insignificant. 10Panx1 showed no significant inhibition of [Ca2+]0-induced ATP release in any types of cells. The results presented here provide compelling evidence that pannexin-1 and CALHM1, which are densely expressed in the porcine bladder, function as ATP release channels in response to bladder distension. Modulation of extracellular Ca2+ may also regulate ATP release in the porcine bladder through voltage-gated CALHM1 ion channels. [ABSTRACT FROM AUTHOR]

Objectives Recently, many epidemiological studies have demonstrated an association between P86L polymorphism of calcium homeostasis modulator 1 (CALHM1) and risk for Alzheimer’s disease (AD). However, the results of these association studies are inconsistent. In this study, we re-evaluated the relation between CALHM1 P86L polymorphism and risk for AD in a meta-analysis. Methods This meta-analysis was performed using the PubMed, Science Direct, Scopus and Google Scholar databases up to June 2015 using the search terms “CALHM1” and “polymorphism or SNP or variant” in combination with “Alzheimer’s disease”. A meta-analysis with pooled odds ratios and 95% confidence intervals was carried out to assess the associations between P86L polymorphism and the risks for Alzheimer’s disease under four genetic models with fixed or random effects models. Results Sixteen studies (twenty-four subgroup studies involving 9795 cases and 15,335 controls) were included in our meta-analysis. Our meta-analysis results indicated that several genetic models of CALHM1 P86L polymorphism were significantly associated with increased risk for AD in overall and Caucasian populations. Conclusions In conclusion, our comprehensive meta-analysis indicated that P86L polymorphism is significantly associated with an increased risk for AD. Our data suggest that CALHM1 polymorphism may be potential biomarker in patients with AD. [ABSTRACT FROM AUTHOR]

Calcium homeostasis modulator 1 (CALHM1), a promising candidate gene for Alzheimer's disease risk, has been recently identified. We tested the hypothesis that the T-allelic variant of the CALHM1 rs2986017 polymorphism confers susceptibility to Alzheimer's disease in a Hungarian case-control sample that was also genotyped for apolipoprotein E. This study included 238 probable patients with Alzheimer's disease who met the diagnostic criteria for National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association and 202 elderly healthy control participants. We failed to detect an association between the CALHM1 polymorphism and the risk for Alzheimer's disease (P=0.153 for genotypes and P=0.090 for alleles), nor did we find an effect on age at onset. However, a potential weak correlation between the presence of the T allele (CT and TT genotypestogether) and Alzheimer's disease was observed (P=0.056). [ABSTRACT FROM AUTHOR]

Abstract: A recent study suggests that the P86L polymorphism (rs2986017) in the calcium homeostasis modulator 1 (CALHM1) gene interferes with calcium homeostasis and increases amyloid β (Aβ) levels. Moreover, in vitro and in vivo data show that both calcium homeostasis and high levels of Aβ play an important role in the induction and maintenance of epileptic seizures in hippocampus, indicating CALHM1 might play a potential role in pathophysiological pathways involved in temporal lobe epilepsy (TLE). The aim of this study was to investigate the genetic contribution of CALHM1 to TLE. Five single-nucleotide polymorphisms (SNPs) of CALHM1 were selected and genotyped using polymerase chain reaction restriction fragment length polymorphism in 560 patients with TLE and 401 healthy controls. We found a positive association between rs11191692 and TLE, but a negative result between rs2986017 and TLE. The rs11191692-A allele frequency was found in 32.4% of the patients and in 26.2% of control subjects (OR=1.35, 95% CI=1.10–1.65, uncorrected P =0.003, corrected P =0.015). Furthermore, the positive association between rs11191692 and TLE independent of apolipoprotein E ε4 was supported by five SNPs haplotype analysis. The results of this study provide the first evidence that the SNP rs11191692 in CALHM1 confers highly increased susceptibility to TLE. [Copyright &y& Elsevier]

A recent study identified a polymorphism (Pro86Leu) in the Calcium homeostasis modulator 1 (CALHM1) gene whose minor Leucine allele showed a higher frequency in Alzheimer's disease (AD) patients compared to controls (29% in AD and 22% in controls). Further studies provided conflicting results in different ethnic groups. In order to assess the involvement of the CALHM1 genetic variant on the risk of developing AD, we analyzed the genotype and allele distributions of the Pro86Leu polymorphism in 758 Italian subjects. Our results did not confirm an association between the CALHM1 variation and AD, thus suggesting a genetic heterogeneity among the various populations. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Mesial temporal lobe epilepsy (MTLE) is one of the most common forms of epilepsies in adults. The calcium homeostasis modulator 1 gene (CALHM1) has been considered one of the candidate genes that play a role in epileptogenesis due to its function in calcium homeostasis and amyloid β (Aβ) regulation. Recently, the association of a single nucleotide polymorphism (rs11191692) of CALHM1 has been reported to be associated with MTLE in Han Chinese, but independent replication is needed. In the present study, rs11191692 and rs2986017 of CALHM1 were determined in 512 MTLE patients and 412 control subjects to investigate the possible involvement of CALHM1 in the etiology of MTLE. Method: Genotyping was determined by polymerase chain reaction-restriction fragment length polymorphism method. Major statistical analyses were performed by SAS. Results: No significant differences in the genotypic or allelic frequencies of both single-nucleotide polymorphisms were revealed between subjects with and without MTLE (rs11191692: P =0.890 and 0.230; rs2986017: P =0.581 and 0.072). Further stratification analysis by gender and age, and analysis of clinical features in relation to MTLE also yielded negative results. Conclusion: rs11191692 and rs2986017 of CALHM1 do not contribute substantially to MTLE in Han Chinese. [Copyright &y& Elsevier]