Repetitive transcranial magnetic stimulation (rTMS) has increasingly been studied over the past decade to determine whether it has a therapeutic benefit on focal cerebral ischemia. However, the underlying mechanism of rTMS in this process remains unclear. In the current study, we investigated the effects of rTMS on the proliferation of adult neural stem cells (NSCs) and explored microRNAs (miRNAs) that were affected by rTMS. Our data showed that 10 Hz rTMS significantly increased the proliferation of adult NSCs after focal cerebral ischemia in the subventricular zone (SVZ), and the expression of miR-25 was obviously up-regulated in the ischemic cortex after rTMS. p57, an identified miR-25 target gene that regulates factors linked to NSC proliferation, was also evaluated, and it exhibited down-regulation. To further verify the role of miR-25, rats were injected with a single dose of antagomir-25 and were subjected to focal cerebral ischemia followed by rTMS treatment. The results confirmed that miR-25 could be repressed specifically and could drive the up-regulation of its target gene (p57), which resulted in the inhibition of adult NSC proliferation in the SVZ after rTMS. Thus, our studies strongly indicated that 10 Hz rTMS can promote the proliferation of adult NSCs in the SVZ after focal cerebral ischemia by regulating the miR-25/p57 pathway.
BackgroundNeural Tube Defects (NTDs) are among the most prevalent and most severe congenital malformations worldwide. Polymorphisms in key genes involving the folate pathway have been reported to be associated with the risk of NTDs. However, the results from these published studies are conflicting. We surveyed the literature (1996–2011) and performed a comprehensive meta-analysis to provide empirical evidence on the association.Methods and FindingsWe investigated the effects of 5 genetic variants from 47 study populations, for a total of 85 case-control comparisons MTHFR C677T (42 studies; 4374 cases, 7232 controls), MTHFR A1298C (22 studies; 2602 cases, 4070 controls), MTR A2756G (9 studies; 843 cases, 1006 controls), MTRR A66G (8 studies; 703 cases, 1572 controls), and RFC-1 A80G (4 studies; 1107 cases, 1585 controls). We found a convincing evidence of dominant effects of MTHFR C677T (OR 1.23; 95%CI 1.07–1.42) and suggestive evidence of RFC-1 A80G (OR 1.55; 95%CI 1.24–1.92). However, we found no significant effects of MTHFR A1298C, MTR A2756G, MTRR A66G in risk of NTDs in dominant, recessive or in allelic models.ConclusionsOur meta-analysis strongly suggested a significant association of the variant MTHFR C677T and a suggestive association of RFC-1 A80G with increased risk of NTDs. However, other variants involved in folate pathway do not demonstrate any evidence for a significant marginal association on susceptibility to NTDs.
Autism spectrum disorder (ASD) is a severe neurological disorder with a high degree of heritability. Reelin gene (RELN), which plays a crucial role in the migration and positioning of neurons during brain development, has been strongly posed as a candidate gene for ASD. Genetic variants in RELN have been investigated as risk factors of ASD in numerous epidemiologic studies but with inconclusive results. To clearly discern the effects of RELN variants on ASD, the authors conducted a meta-analysis integrating case-control and transmission disequilibrium test (TDT) studies published through 2001 to 2013. Odds ratios (ORs) with 95% confidence intervals were used to estimate the associations between three RELN variants (rs736707, rs362691, and GGC repeat variant) and ASD. In overall meta-analysis, the summary ORs for rs736707, rs362691, and GGC repeat variant were 1.11 [95% confidence interval (CI): 0.80-1.54], 0.69 (95% CI: 0.56-0.86), and 1.09 (95% CI: 0.97-1.23), respectively. Besides, positive result was also obtained in subgroup of broadly-defined ASD for rs362691 (OR = 0.67, 95% CI: 0.52-0.86). Our meta-analysis revealed that the RELN rs362691, rather than rs736707 or GGC repeat variant, might contribute significantly to ASD risk.
Cognitive impairment is a serious mental deficit caused by stroke that can severely affect the quality of a survivor's life. Repetitive transcranial magnetic stimulation (rTMS) is a well-known rehabilitation modality that has been reported to exert neuroprotective effects after cerebral ischemic injury. In the present study, we evaluated the therapeutic efficacy of rTMS against post-stroke cognitive impairment (PSCI) and investigated the mechanisms underlying its effects in a middle cerebral artery occlusion (MCAO) rat model. The results showed that rTMS ameliorated cognitive deficits and tended to reduce the sizes of cerebral lesions. In addition, rTMS significantly improved cognitive function via a mechanism involving increased neurogenesis and decreased apoptosis in the ipsilateral hippocampus. Moreover, brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase B (TrkB), were clearly upregulated in ischemic hippocampi after treatment with rTMS. Additionally, further studies demonstrated that rTMS markedly enhanced the expression of the apoptosis-related B cell lymphoma/leukemia gene 2 (Bcl-2) and decreased the expression of the Bcl-2-associated protein X (Bax) and the number of TUNEL-positive cells in the ischemic hippocampus. Both protein levels and mRNA levels were investigated. Our findings suggest that after ischemic stroke, treatment with rTMS promoted the functional recovery of cognitive impairments by inhibiting apoptosis and enhancing neurogenesis in the hippocampus and that this mechanism might be mediated by the BDNF signaling pathway.
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