Attenuation of Corpus Callosum Axon Myelination and Remyelination in the Absence of Circulating Sex Hormones

Sex differences in the structure and organization of the corpus callosum (CC) can be attributed to genetic, hormonal or environmental effects, or a combination of these factors. To address the role of gonadal hormones on axon myelination, functional axon conduction and immunohistochemistry analysis of the CC in intact, gonadectomized and hormone‐replaced gonadectomized animals were used. These groups were subjected to cuprizone diet‐induced demyelination followed by remyelination. The myelinated component of callosal compound action potential was significantly decreased in ovariectomized and castrated animals under normal myelinating condition. Compared to gonadally intact cohorts, both gonadectomized groups displayed more severe demyelination and inhibited remyelination. Castration in males was more deleterious than ovariectomy in females. Callosal conduction in estradiol‐supplemented ovariectomized females was significantly increased during normal myelination, less attenuated during demyelination, and increased beyond placebo‐treated ovariectomized or intact female levels during remyelination. In castrated males, the non‐aromatizing steroid dihydrotestosterone was less efficient than testosterone and estradiol in restoring normal myelination/axon conduction and remyelination to levels of intact males. Furthermore, in both sexes, estradiol supplementation in gonadectomized groups increased the number of oligodendrocytes. These studies suggest an essential role of estradiol to promote efficient CC myelination and axon conduction in both sexes.     

β-石竹烯对小鼠脑缺血/再灌注白质损伤的保护作用研究

目的研究β-石竹烯(β-caryophyllene,BCP)对小鼠脑缺血/再灌注(cerebral ischemia-reperfusion,CIR)白质损伤的保护作用。方法随机将C57BL/6小鼠分为正常对照组(Control)、模型组(CIR)、治疗组(36、72、144 mg·kg^-1)。线栓法建立小鼠大脑中动脉栓塞(middle cerebral artery oc-clusion,MCAO)模型。缺血1 h,再灌注24 h,TTC染色确定脑梗死体积,并进行神经行为学评分;干湿重法测脑含水量;HE染色及透射电镜观察胼胝体损伤情况;Luxol Fast Blue(LFB)染色标记脑神经髓鞘;Western blot测胼胝体髓鞘碱性蛋白(mbp)、神经丝蛋白(NF)、Bcl-2、Bax和caspase-3的表达。结果与模型组比较,BCP可降低神经行为学评分,减小脑梗死体积,减轻脑水肿和胼胝体髓鞘损伤,升高髓鞘染色光密度(optical density,OD),上调mbp、NF、Bcl-2表达,降低Bax和caspase-3表达。结论BCP对小鼠脑缺血/再灌注白质损伤有保护作用,可能与Bax/Bcl-2凋亡通路有关。     

Polymicrogyria with dysmorphic basal ganglia? Think tubulin!

Dominant mutations in TUBB2B have been reported in patients with polymicrogyria. We further explore the phenotype associated with mutations in TUBB2B. Twenty patients with polymicrogyria (five unilateral) were tested for mutations in TUBB2B by Sanger sequencing. We identified two novel de novo mutations, c.743C>T (p.Ala248Val) and c.1139G>T (p.Arg380Leu) in exon 4 of TUBB2B in three unrelated families. Brain magnetic resonance images showed polymicrogyria involving predominantly the perisylvian regions. In addition, there was a dysmorphic appearance of the basal ganglia, thin corpus callosum, enlargement of the ventricles, thinning of the white matter and hypoplasia of pons and cerebellar vermis. This combination of associated features was absent in all 17 patients with polymicrogyria in whom no mutation was identified. This report underlines that the association of polymicrogyria with thin or absent corpus callosum, dysmorphic basal ganglia, brainstem and vermis hypoplasia is highly likely to result from mutations in TUBB2B and provides further insight in how mutations in TUBB2B affect protein function.     

The effect of corpus luteum on hormonal composition of follicular fluid from different sized follicles and their relationship to serum concentrations in dairy cows

ObjectiveTo investigate the effect of the presence or absence of corpus luteum on hormonal composition of follicular fluid (FF) from different sized follicles and their relationship to serum concentrations in dairy cows.MethodsOvaries were collected from 30 clinically healthy adult female cows (Holstein Friesian) 4–7 years of age with clinically normal reproductive tracts after slaughtering. Blood samples were collected from the jugular vein before slaughter from each cow. The stage of the cycle in the cows was determined postmortem. The ovaries collected from per cow were classified with corpus luteum (CL⁺) and without corpus luteum (CL⁻). FF was aspirated from small (3-5 mm), medium (6-9 mm), and large (10-20 mm) follicles in CL⁺ and CL⁻ ovaries. Serum and FF samples were analyzed for estradiol-17β, progesterone, testosterone, T₃ and T₄ concentrations.ResultsResults demonstrated that the FF concentrations of estradiol-17β, progesterone and testosterone in different sized follicles categories (small, medium and large follicles in CL⁺ and CL⁻ ovaries) were significantly higher (P≤0.05) when compared with the serum. The FF concentrations of estradiol-17β and testosterone in same follicle size categories in CL⁺ and CL⁻ ovaries were also significant (P<0.05). Indeed, concentrations of these hormones in the CL⁻ ovaries were higher than those of the CL⁺ ovaries. However, there was a statistically significant difference between medium and large follicles for progesterone concentration in CL⁺ and CL⁻ ovaries (P<0.05). There was a significant correlation between concentration of hormones in serum and FF with increased follicular diameter.ConclusionsThese results indicated that the levels of hormonal composition in the FF were related to follicular size and interestingly to the presence or absence of a corpus luteum. Indeed, the corpus luteum locally affects neighboring follicular compositions during the luteal phase of the estrous cycle in dairy cows.     

Agenesis of the corpus callosum: symptoms consistent with developmental disability in two siblings

Agenesis of the corpus callosum (AgCC) is a congenital disorder that disrupts the development of neurological structures connecting the right and left hemispheres of the brain. In addition to neurological symptoms, many individuals with AgCC demonstrate marked deficits in social, communication, and adaptive skills. This paper presents two case studies of congenital AgCC in siblings with socioemotional and behavioral symptoms consistent with developmental disability, but with notably different symptom presentations and clinical needs. Conclusions from these cases suggest that unique symptom profiles of individuals with AgCC warrant careful consideration for referral to appropriate academic and habilitative services.     

160 kb deletion in ISPD unmasking a recessive mutation in a patient with Walker–Warburg syndrome

Walker–Warburg syndrome (WWS) is a severe muscular dystrophy with eye and brain malformations. On a molecular level, WWS is a disorder of the O-linked glycosylation of α-dystroglycan and therefore referred to as one of the dystroglycanopathies. The disease family of muscular dystrophy–dystroglycanopathy (MDDG) contains a spectrum of severe to mild disorders, designated as MDDG type A to C. WWS, as the most severe manifestation, corresponds to MDDG type A. Defects in the genes POMT1, POMT2, POMGNT1, FKTN, FKRP, LARGE, GTDC2, G3GALNT2, GMPPB, B3GNT1, TMEM5 and COL4A1 and ISPD have been described as causal for several types of MDDG including WWS, but can only be confirmed in about 60–70% of the clinically diagnosed individuals. The proteins encoded by these genes are involved in the posttranslational modification of α-dystroglycan. Mutations in POMT1, POMT2, POMGNT1, FKTN, FKRP, LARGE, GMPPB, TMEM5 and COL4A1 and ISPD lead to a wide spectrum of phenotypes of congenital muscular dystrophies with or without eye and brain abnormalities. Patients with WWS frequently demonstrate a complete lack of psychomotor development, severe eye malformations, cobblestone lissencephaly and a hypoplastic cerebellum and brainstem, seizures, hydrocephalus and poor prognosis. Here, we present a boy with WWS who showed compound heterozygous changes in ISPD and discuss the clinical and radiological phenotype and the molecular genetic findings, including a novel pathogenic mutation in ISPD.     

胼胝体变性六例影像学特点和临床表现

目的 探讨胼胝体变性(Marchiafava-Bignami disease,MBD)的影像学特点和临床表现.方法 对我院诊治的6例MBD患者进行回顾性分析,包括影像学检查(如头颅CT、MRI)、实验室检查、临床症状和随访情况.结果 6例患者MRI检查均表现为胼胝体肿胀及T1WI等或低信号,T2WI高信号,液体衰减反转恢复序列高信号,弥散加权成像示弥散受限.其中例1、例4和例6以急性意识障碍起病,CT和MRI检查除累及整个胼胝体外双侧半卵圆区也受累,预后较差.例2和例3以反应迟钝、记忆力下降起病,CT和MRI检查病变主要累及胼胝体膝部和压部,经积极治疗,患者基本恢复正常.例5以双下肢麻木无力、反应迟钝起病,MRI检查病变累及胼胝体压部及体部,经治疗后也恢复正常.结论 MBD临床表现复杂,但具有特征性影像学表现,其起病形式和影像学特征可作为反映其预后的重要因素之一.     

奥氮平诱导性肥胖大鼠血清和纹状体TNF—α表达变化

目的观察奥氮平诱导性肥胖大鼠血清和大脑纹状体肿瘤坏死因子-α（TNF-α）含量的影响。方法40只SD雄性大鼠随机分为对照组和奥氮平组,各20只,前者采用普通饲料喂养,后者在普通饲粮喂养基础上灌胃奥氮平（1．2mg·kg^-1）4周建立奥氮平诱导肥胖大鼠。采用酶联免疫测定法测定血清中TNF-α的含量,生化比色法测定血清葡萄糖（FBS）含量,对脑组织采用HE染色观察形态学变化,采用免疫组织化学方法观察两组大鼠脑组织中TNF-α的表达。结果与对照组比较,奥氮平组大鼠的体重、血糖、血脂和血清TNF-α水平和纹状体TNF-α蛋白表达均有不同程度的升高,差异有统计学意义（P〈0．01）。结论奥氮平可以导致大鼠体重增加,糖脂代谢紊乱,血清及纹状体TNF-α升高,通过调节TNF-α异常变化可能改善奥氮平诱导肥胖大鼠中枢摄食活动。