A genotyping study of 13 cases of early-onset Charcot-Marie-Tooth disease / 中国当代儿科杂志

OBJECTIVE@#To study the clinical characteristics and genetic variation of early-onset Charcot-Marie-Tooth disease (CMT).@*METHODS@#Children with a clinical diagnosis of early-onset CMT were selected for the study. Relevant clinical data were collected, and electromyogram and CMT-related gene detection were performed and analyzed.@*RESULTS@#A total of 13 cases of early-onset CMT were enrolled, including 9 males (69%) and 4 females (31%). The mean age at consultation was 4.0±2.1 years. Among them, 12 children (92%) had an age of onset less than 2 years, 9 children (69%) were diagnosed with CMT type 1 (including 6 cases of Dejerine-Sottas syndrome), 1 child (8%) with intermediate form of CMT, and 3 children (23%) with CMT type 2. The genetic test results of these 13 children showed 6 cases (46%) of PMP22 duplication mutation, 3 cases (23%) of MPZ gene insertion mutation and point mutation, 3 cases (23%) of MFN2 gene point mutation, and 1 case (8%) of NEFL gene point mutation. Eleven cases (85%) carried known pathogenic mutations and 2 cases (15%) had novel mutations. The new variant c.394C>G (p.P132A) of the MPZ gene was rated as "possibly pathogenic" and the new variant c.326A>G (p.K109R) of the MFN2 gene was rated as "pathogenic".@*CONCLUSIONS@#Early-onset CMT is mainly caused by PMP22 gene duplication mutation and MPZ gene mutations. The clinical phenotype is mainly CMT type 1, among which Dejerine-Sottas syndrome accounts for a considerable proportion.

Cannabinoid receptor 1 expression and pathological changes in rat hippocampus after deprivation of rapid eye movement sleep / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To observe the expression of cannabinoid receptor 1 (CB1R) mRNA and pathological changes in rat hippocampus after deprivation of rapid eye movement (REM) sleep.</p><p><b>METHODS</b>Totally 42 Sprague-Dawley male rats were randomly divided into cage control (CC), tank control (TC) and the sleep deprivation groups (SD). The SD and TC rats were sacrificed at the end of 1 d, 3 d and 5 d sleep deprivation periods, respectively. The modified multiple platform methods were established for the REM sleep deprivation. CB1R mRNA was measured by reverse transcription-polymerase chain reaction (RT-PCR). The hippocampus sections of different stages were observed with electron microscope.</p><p><b>RESULT</b>In SD 1 d group, the expression of CB1R mRNA was significantly increased compared with the CC, TC, SD 3 d and SD 5 d groups (P <0.05) while in SD 3 d group it was reduced. The expression of CB1R mRNA of SD 5 d group was significantly higher than that of the SD 3 d group (P <0.05). Neuron apoptosis was found in SD 3 d and SD 5 d groups.</p><p><b>CONCLUSION</b>Sleep deprivation can cause brain injury with the changes of CB1R mRNA expression.</p>

Time-course of mu-calpain activation, c-Fos, c-Jun, HSP70 and HSP27 expression in hypoxic-ischemic neonatal rat brain / 中华儿科杂志

<p><b>OBJECTIVE</b>The cascade of physiological events underlying hypoxic-ischemic brain damage (HIBD) remains to be fully established. The perinatal brain shows both an increased tolerance to hypoxic-ischemic (HI) injury and a faster and more complete recovery than the adult. It is, therefore, important to understand the sequence of events following hypoxia and ischemia in young animals. The present study aimed to clarify the time-course of the activation of the mu-calpain, and the expression of c-Fos, c-Jun, HSP70 and HSP27 proteins following severe HI (2 h hypoxia) and their relationship with each other.</p><p><b>METHODS</b>A modified newborn rat model of HIBD that included a combination of hypoxia and ischemia as described by Rice was used. Forty-two postnatal 7-day-old Sprague-Dawley rats were randomly divided into seven groups (6 rats in each): 6 time-window groups and a normal control group. Samples were collected at 0, 1, 2, 4, 12 and 24 h after HI insults. The protein concentration was determined using a modified Bradford assay. mu-calpain activation, c-Fos, c-Jun, HSP70 and HSP27 expressions were observed respectively by Western blot from cortical and hippocampal samples.</p><p><b>RESULTS</b>The cleavage of cytosolic mu-calpain was observed from both cortical and hippocampal samples in neonatal rats after HI. The ratio 76:80 of mu-calpain was increased significantly post-HI and reached a maximum at 24 h in cortex and at 12 h in hippocampus after HI. The expressions of c-Fos and c-Jun from both cortical and hippocampal samples in neonatal rats were up-regulated and peaked at 2 or 4 h after HI, demonstrating significant differences at 1, 2, 4, and 12 h compared with that observed in the control (P < 0.05). When compared with that observed in cortex, the nuclear c-Fos expression from hippocampal samples was highly elevated at 2, 4 and 12 h but significantly decreased at 24 h after HI (P < 0.05), while the nuclear c-Jun expression from hippocampal samples was highly elevated at 0 and 1 h but significantly decreased at 4 and 24 h after HI (P < 0.05). Similarly, the expressions of HSP70 and HSP27 from both cortical and hippocampal samples were up-regulated and reached a maximum at 12 or 24 h after HI, demonstrating significant differences at 12 or 24 h both in cortex and hippocampus for HSP70, and at 24 h in cerebral cortex as well as at 12 and 24 h in hippocampus for HSP27 compared with the control (P < 0.05). Furthermore, in comparison with that observed in cortex, the HSP70 expression from hippocampal samples was highly elevated at 1 h, but significantly decreased at 4, 12 and 24 h after HI (P < 0.05), while the HSP27 expression was permanently elevated in hippocampus after HI.</p><p><b>CONCLUSION</b>The neuronal injury induced by HI insults appears to involve many ongoing and simultaneous mechanisms. HI activates the calpains immediately, which may contribute to neuron apoptosis, and induces a significant brain neuroprotection, since there is an increased HSP70 expression and a relatively late remarkable HSP27 expression in hypoxic-ischemic neonatal rat brain. Nuclear c-Fos and c-Jun may participate in the pathogenesis of HIBD.</p>