The role of microRNAs in the pathophysiology of human central nervous system: A focus on neurodegenerative diseases.

microRNAs (miRNAs) are suggested to play substantial roles in regulating the development and various physiologic functions of the central nervous system (CNS). These include neurogenesis, cell fate and differentiation, morphogenesis, formation of dendrites, and targeting non-neural mRNAs. Notably, deregulation of an increasing number of miRNAs is associated with several neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis and CNS tumors. They are particularly known to affect the amyloid ß (Aß) cleavage and accumulation, tau protein homeostasis, and expression of alpha-synuclein (α-syn), Parkin, PINK1, and brain-derived neurotrophic factor (BDNF) that play pivotal roles in the pathogenesis of neurodegenerative diseases. These include miR-16, miR-17-5p, miR-20a, miR-106a, miR-106b, miR-15a, miR-15b, miR-103, miR-107, miR-298, miR-328, miR-195, miR-485, and miR-29. In CNS tumors, several miRNAs, including miR-31, miR-16, and miR-21 have been identified to modulate tumorigenesis through impacting tumor invasion and apoptosis. In this review article, we have a look at the recent advances on our knowledge about the role of miRNAs in human brain development and functions, neurodegenerative diseases, and their clinical potentials.

Potential role of FKBP5 single-nucleotide polymorphisms in functional seizures.

OBJECTIVE: We investigated the associations between FKBP5 single-nucleotide polymorphisms (SNPs) and functional seizures (FS). METHODS: Seventy patients with FS, 140 with major depressive disorder (MDD), and 140 healthy controls were studied. Their DNAs were analyzed for the rs1360780 in the 3' region and rs9470080 in the 5' region of the FKBP5. Childhood trauma questionnaire and hospital anxiety and depression scale were used. RESULTS: Patients with FS and those with MDD had less GG and more AA genotypes in both rs9470080 and rs1360780 SNPs compared with those in healthy controls. Similar results were observed for allelic frequencies. There were no significant differences between FS and MDD groups in terms of genotype and allelic frequencies for both SNPs. The results of multinomial logistic regression analysis showed that FKBP5 polymorphisms were not associated with the diagnosis. SIGNIFICANCE: Patients with FS and those with MDD had significantly different genotypes in both rs9470080 and rs1360780 SNPs compared with those in healthy controls. However, it seems that FKBP5 polymorphisms were not associated with FS in the absence of depression. Further genetic investigations of patients with FS may increase our understanding of the neurobiological underpinnings of this condition, but such studies should be large enough and very well designed; they should include a comparison group with depression in addition to a healthy control group.

Migraine and gastric disorders: Are they associated?

BACKGROUND: Migraine is a common disorder which affects quality of life. There has been an increasing interest for discovering the association of gastrointestinal (GI) disorders with migraine during past years. This study aims to evaluate the association of Helicobacter pylori contamination, gastroesophageal reflux disease (GERD), gastric ulcer (GU), and duodenal ulcer (DU) with migraine in patients who underwent upper GI endoscopy due to refractory dyspepsia. MATERIALS AND METHODS: In this observational cross-sectional study, 341 dyspeptic patients who underwent upper GI endoscopy in Shahid Beheshti Hospital, Qom, Iran, included during 2016-2018. A checklist was used for collecting demographics, symptoms, and results from endoscopy and H. pylori testing. Diagnosis of migraine was made according to the International Headache Society criteria in patients who had headache. Data were analyzed using Chi-square and independent samples t-tests in SPSS 16 (SPSS Inc., Chicago, IL, USA) with P < 0.05 as significance level. RESULTS: Among 341 patients, 141 (% 41.3) were male and 200 (58.7%) were female. 149 (43.7%) patients were diagnosed with migraine, from which 48 (32.2%) were male and 101 (67.8%) were female. The observed difference in migraine prevalence among male and female was statistically significant (P = 0.003). 198 (58.06%) patients were H. pylori contaminated, among these 138 (69.7%) suffered from migraine. Among 143 H. pylori-negative patients, there were 11 (7.7%) migraineurs. The difference in the prevalence of migraine among H. pylori positive and negative patients was significant. H. pylori and GERD were associated with migraine with P < 0.001. Patients with DU were more commonly suffering from migraine (P = 0.001). The association in patients with GU was not statistically significant (P = 0.863). CONCLUSION: Migraine might be associated with GERD, H. pylori infection, and DU, and the treatment of the underlying GI disorder may control headaches.

Myasthenia gravis development and crisis subsequent to multiple sclerosis.

During the last decade, sporadic combination of multiple sclerosis (MS) and myasthenia gravis (MG) has been reported repeatedly. Although these are anecdotal, they are important enough to raise concerns about co-occurrence of MG and MS. Here, we present a case of an MS patient who developed an MG crisis. She had received interferon for relapsing remitting MS. Interestingly, she developed an MG crisis 4 years after the diagnosis of MS. MS and MG have relatively the same distribution for age, corresponding to the younger peak of the bimodal age distribution in MG. They also share some HLA typing characteristics. Furthermore, some evidences support the role of systemic immune dysregulation due to a genetic susceptibility that is common to these two diseases. The association may be underdiagnosed because of the possible overlap of symptoms especially bulbar manifestations in which either MG or MS can mimic each other, leading to underestimating incidence of the combination. The evidence warrants physicians, especially neurologists, to always consider the possibility of the other disease when encountering any patients either with MS or MG. Anecdotal and sporadic reports of combination of multiple sclerosis (MS) and myasthenia gravis (MG) have been raised concerns about co-occurrence of them.