Anti-LINGO-1 antibody ameliorates cognitive impairment, promotes adult hippocampal neurogenesis, and increases the abundance of CB1R-rich CCK-GABAergic interneurons in AD mice.

In view of the negative regulatory effect of leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 1 (LINGO-1) on neurons, an antibody against LINGO-1 (anti-LINGO-1 antibody) was herein administered to 10-month-old APP/PS1 transgenic Alzheimer's disease (AD) mice for 2 months as an experimental intervention. Behavioral, stereology, immunohistochemistry and immunofluorescence analyses revealed that the anti-LINGO-1 antibody significantly improved the cognitive abilities, promoted adult hippocampal neurogenesis (AHN), decreased the amyloid beta (Aß) deposition, enlarged the hippocampal volume, and increased the numbers of total neurons and GABAergic interneurons, including GABAergic and CCK-GABAergic interneurons rich in cannabinoid type 1 receptor (CB1R), in the hippocampus of AD mice. In contrast, this intervention significantly reduced the number of GABAergic interneurons expressing LINGO-1 and CB1R in the hippocampus of AD mice. More importantly, we also found a negative correlation between LINGO-1 and CB1R on GABAergic interneurons in the hippocampus of AD mice, while the anti-LINGO-1 antibody reversed this relationship. These results indicated that LINGO-1 plays an important role in the process of hippocampal neuron loss in AD mice and that antagonizing LINGO-1 can effectively prevent hippocampal neuron loss and promote AHN. The improvement in cognitive abilities may be attributed to the improvement in AHN, and in the numbers of GABAergic interneurons and CCK-GABAergic interneurons rich in CB1Rs in the hippocampus of AD mice induced by the anti-LINGO-1 antibody. Collectively, the double target effect (LINGO-1 and CB1R) initiated by the anti-LINGO-1 antibody may provide an important basis for the study of drugs for the prevention and treatment of AD in the future.

Discordant intrauterine transfusion in dichorionic twin pregnancy with Rh isoimmunization.

Discordant intrauterine transfusion (IUT) in twin pregnancy with Rh isoimmunization is uncommon and complicated. We report a gravida 3, para 2 woman with a dichorionic diamniotic (DCDA) twin pregnancy and two fetuses received discordant transfusions. Middle cerebral artery peak systolic velocity (MCA-PSV) was used to evaluate the anemic degree in each foetus. IUT was performed 3 times in twin A and 4 times in twin B to reverse foetal anaemia. Transfusions were distinct due to the different tolerance to IUT, and the procedure could be continued in one foetus even if the other one underwent complications. Two male babies were born at 36 weeks of gestation and were given different treatments after birth. Twins were subsequently healthy after 2 years of follow up. The discordant IUT was due to the different tolerance to transfusion in the DCDA twins. Zygosity is important for the management and treatment of haemolytic anaemia in twin pregnancies.

Antagonizing LINGO-1 reduces activated microglia and alleviates dendritic spine loss in the hippocampus of APP/PS1 transgenic mice.

In Alzheimer's disease (AD), microglia are involved in synaptic pruning and mediate synapse loss. LINGO-1 is a negative regulator of nerve growth, and whether antagonizing LINGO-1 can attenuate synaptic pruning by microglia and rescue dendritic spines in the hippocampus in AD is still unclear. On this basis, the anti-LINGO-1 antibody, which binds to LINGO-1 protein and antagonizes the effects of LINGO-1, was administered to 10-month-old APP/PS1 transgenic mice for 2 months. The Morris water maze test, immunohistochemical and stereological methods, immunofluorescence and 3D reconstruction were used. Compared to wild-type mice, APP/PS1 transgenic mice had worse performance on behavioral tests, fewer dendritic spines but more microglia in the hippocampus. Meanwhile, the microglia in APP/PS1 transgenic mice had more branches of medium length (4-6 µm) and a cell body area with greater variability. Moreover, APP/PS1 transgenic mice had more postsynaptic termini colocalized with microglia in the hippocampus than wild-type mice. The anti-LINGO-1 antibody significantly reversed these changes in AD, indicating that the anti-LINGO-1 antibody can improve hippocampus-dependent learning and memory abilities and effectively rescue dendritic spines in the hippocampus of AD mice and that microglia might participate in this progression in AD. These results provide a scientific basis for further studying the mechanism of the anti-LINGO-1 antibody in AD and help to elucidate the role of LINGO-1 in the treatment of AD.

[Perinatal outcome of monochorionic diamniotic twins with selective intrauterine growth restriction].

OBJECTIVE: To evaluate the perinatal outcome of three types of monochorionic diamniotic (MCDA) twins with selective intrauterine growth restriction (sIUGR). METHODS: From January 2005 to June 2012, clinical data of 42 pairs of MCDA twins (84 fetuses) with sIUGR and 71 pairs of normal MCDA twins (142 fetuses) in the same period were analyzed retrospectively in the First Affiliated Hospital of Sun Yat-Sen University. Fetuses with sIUGR were classified into three groups based on umbilical artery Doppler flow.There were 25 cases of type I, 11 cases of type II and 6 cases of type III. The perinatal outcome was compared between sIUGR and normal MCDA twins, and among the three types of sIUGR as well. Perinatal outcomes included gestational age at delivery, rate of intrauterine fetal death (IUFD), birth weight, intertwin discordance of birth weight, neonatal death and survival rate at 6 months. RESULTS: (1) The gestational age of sIUGR at delivery was significantly earlier than the control group [(34±3), (36±2) weeks, respectively], and the rate of IUFD of both fetuses of sIUGR was significantly higher (4.8%, 0, respectively). In the sIUGR group, the average birth weight of large or small twins [(2130±350), (1520±400) g, respectively] was smaller than those in the control group [(2470±500), (2340±460) g, respectively]. The difference was statistically significant (P<0.05, P<0.01, respectively). The intertwin discordance of birth weight in sIUGR group was significantly larger (27.6%) than the control group (4.0%, P<0.01). (2) The gestational age at delivery in type II and type III [(34±5), (34±2) weeks, respectively] was significantly earlier than the control group (P<0.05). The rate of IUFD of both fetuses in type II (18%) was significantly higher than in type I (0) and the control group (0, P<0.05). In sIUGR group, the average birth weight of small twins in type I, type II and type III was (1640±430), (1330±310) and (1500±380) g respectively, all of which were significantly smaller than that in the control group (P<0.05). The average birth weight of small twins in type II was smaller than in type I and the difference was statistically significant (P<0.05). In sIUGR group, the intertwin discordance of birth weight in type I, type II and type III was 24.1%, 34.6%, 31.3% respectively, all of which were significantly larger than that in the control group (4.0%, P<0.05). There were no statistically significant differences of the intertwin discordance of birth weight among the three types of sIUGR (P>0.05). Survival rate at 6 months in type II (64%) was significantly lower than in type I (92%) and the control group (91.5%, P<0.01). CONCLUSIONS: The perinatal outcome of MCDA twins with sIUGR is poor. The outcome is different among the three types of sIUGR, and typeIIis the worst. Type II is associated with a high risk of intrauterine fetal demise. It is important to monitor the intrauterine situation closely.

Anti-LINGO-1 antibody protects neurons and synapses in the medial prefrontal cortex of APP/PS1 transgenic mice.

The medial prefrontal cortex (mPFC), one of the most vulnerable brain regions in Alzheimer's disease (AD), plays a critical role in cognition. Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein-1 (LINGO-1) negatively affects nerve growth in the central nervous system; however, its role in the pathological damage to the mPFC remains to be studied in AD. In this study, an anti-LINGO-1 antibody was administered to 10-month-old APP/PS1 mice, and behavioral tests, stereological methods, immunohistochemistry and immunofluorescence were used to answer this question. Our results revealed that LINGO-1 was highly expressed in the neurons of the mPFC of AD mice, and the anti-LINGO-1 antibody improved prefrontal cortex-related function and reduced the protein level of LINGO-1, atrophy of the volume, Aß deposition and massive losses of synapses and neurons in the mPFC of AD mice. Antagonizing LINGO-1 could effectively alleviate the pathological damage in the mPFC of AD mice, which might be an important structural basis for improving prefrontal cortex-related function. Abnormal expression of LINGO-1 in the mPFC may be one of the key targets of AD, and the effect initiated by the anti-LINGO-1 antibody may provide an important basis in the search for drugs for the prevention and treatment of AD.

[Expression and methylated regulation of HERVWE1 in placenta of monozygotic discordant twins].

OBJECTIVE: To explore the HERVWE1 gene expression in the placentas of discordant monozygotic twins and identify its regulation by methylation. METHODS: Fetuses from 21 pairs of monozygotic discordant twins were marked as "smaller" or "larger" according to birth weight. Placental HERVWE1 mRNA and protein expression profiles were analyzed by quantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) stain. Methylation profiles of the HERVWE1 promoter region were analyzed by COBRA, MSP-PCR and pyrosequencing assay. RESULTS: In discordant twins group, the mean methylation level of the HERVWE1 promoter region decreased in smaller fetuses (P < 0.05). And there were increased mRNA and protein levels of HERVWE1 in smaller fetuses versus larger counterparts (P < 0.05). CONCLUSION: In discordant monozygotic twins, the HERVWE1 expression is higher in smaller fetuses and lower in larger counterparts. Methylation of HERVWE1 gene promoter region may participate in the regulation of HERVWE1 gene expression in twins.

[Intrauterine growth characteristics of twins and those twins discordant birthweight].

OBJECTIVE: To investigate the intrauterine growth characteristics of twins and birthweight discordant twins (discordant twins). METHODS: Total of 1010 twin pregnancies (2020 fetuses) with complete delivery records from the Department of Obstetrics and Gynecology, the First and Third Affiliated Hospital of SUN Yat-sen University between January 1, 2000 and July 31, 2010 were studied retrospectively. One handred and ninteen cases (238 fetuses) with intrapair birthweight difference ≥ 25% were determined as the discordant twins group, and the other 891 cases (1782 fetuses) with intrapair birthweight difference < 25% were identified as the concordant twins group. The singleton control group included 4042 singleton pregnancies in the same period. RESULTS: (1) Comparison of clinical data between the twins groups: the birthweight of larger-twin, smaller-twin and intrapair birthweight difference in the discordant twins group and the concordant twins group were (2090 ± 827) g, (1392 ± 592) g, (33.9 ± 9.3)%, and (2408 ± 543) g, (2191 ± 505) g, (8.9 ± 6.5)%, respectively, with significant differences (P < 0.01). The incidence of discordant twins was 11.78% (119/1010). Compared with the concordant twins group, the discordant twins group had higher proportion of monochorionic twins, and higher prevalence of pregnancy complications such as late miscarriage, abnormal umbilical insertion, twin-twin transfusion syndrome and hypertensive disorders in pregnancy (P < 0.05). (2) The characteristics of twin birthweight distribution: 1) In all the 2020 twins, 80.05% (1617/2020) fetuses had birthweight below the 50(th) percentile of the singleton control group, while 23.71% (479/2020) feeuses got birthweight below the 10(th) percentile of the singleton control group. 2) After 19(th) gestational week, the 50(th) and 90(th) percentile of all twins' birthweight were lower than those of singletons. After 38(th) gestational week, the birthweight of singletons kept increasing and reached its peak at 41(th) week, while the birthweight of twins reached its peak at 38(th) week, followed by a decline at 39 weeks, which was even lower than the 10(th) percentile of the singleton control group. 3) The distribution of birthweight of larger- and smaller-twin in the discordant twins group: 65 (54.6%, 65/119) larger-twins and one (0.8%, 1/119) smaller-twin had birthweight above the 50(th) percentile of all twins, while 5 (4.2%, 5/119) larger-twins and 97 (81.5%, 97/119) smaller-twins got birthweight below the 10(th) percentile of all twins. CONCLUSIONS: (1) The patterns of birthweight curves for each gestational week are different between twins and singletons. In order to evaluate the growth of twins, birthweight reference for twins should be employed. (2) According to the reference of twins birthweight, the most discordant twins are complicated with fetal growth restriction at least in one twin.

Exercise more efficiently regulates the maturation of newborn neurons and synaptic plasticity than fluoxetine in a CUS-induced depression mouse model.

Depression, a common and important cause of morbidity and mortality worldwide, is commonly treated with antidepressants, electric shock and psychotherapy. Recently, increasing evidence has shown that exercise can effectively alleviate depression. To determine the difference in efficacy between exercise and the classic antidepressant fluoxetine in treating depression, we established four groups: the Control, chronic unpredictable stress (CUS/STD), running (CUS/RUN) and fluoxetine (CUS/FLX) groups. The sucrose preference test (SPT), the forced swimming test (FST), the tail suspension test (TST), immunohistochemistry, immunofluorescence and stereological analyses were used to clarify the difference in therapeutic efficacy and mechanism between exercise and fluoxetine in the treatment of depression. In the seventh week, the sucrose preference of the CUS/RUN group was significantly higher than that of the CUS/STD group, while the sucrose preference of the CUS/FLX group did not differ from that of the CUS/STD group until the eighth week. Exercise reduced the immobility time in the FST and TST, while fluoxetine only reduced immobility time in the TST. Hippocampal structure analysis showed that the CUS/STD group exhibited an increase in immature neurons and a decrease in mature neurons. Exercise reduced the number of immature neurons and increased the number of mature neurons, but no increase in the number of mature neurons was observed after fluoxetine treatment. In addition, both running and fluoxetine reversed the decrease in the number of MAP2+ dendrites in depressed mice. Exercise increased the number of spinophilin-positive (Sp+) dendritic spines in the hippocampal CA1, CA3, and dentate gyrus (DG) regions, whereas fluoxetine only increased the number of SP+ spines in the DG. In summary, exercise promoted newborn neuron maturation in the DG and regulated neuronal plasticity in three hippocampal subregions, which might explain why running exerts earlier and more comprehensive antidepressant effects than fluoxetine.

Running exercise protects spinophilin-immunoreactive puncta and neurons in the medial prefrontal cortex of APP/PS1 transgenic mice.

The medial prefrontal cortex (mPFC) is thought to be closely associated with emotional processes, decision making, and memory. Previous studies have identified the prefrontal cortex as one of the most vulnerable brain regions in Alzheimer's disease (AD). Running exercise has widely been recognized as a simple and effective method of physical activity that enhances brain function and slows the progression of AD. However, the effect of exercise on the mPFC of AD is unclear. To address these issues, we investigated the effects of 4 months of exercise on the numbers of spinophilin-immunoreactive puncta and neurons in the mPFC of 12-month-old APPswe/PSEN1dE9 (APP/PS1) transgenic AD model mice using stereological methods. The spatial learning and memory abilities of mice were tested using the Morris water maze. Four months of running exercise delayed declines in spatial learning and memory abilities. The stereological results showed significantly lower numbers of spinophilin-immunoreactive puncta and neurons in the mPFC of APP/PS1 mice than in the wild-type control group. The numbers of spinophilin-immunoreactive puncta and neurons in the mPFC of running APP/PS1 mice were significantly greater than those in the APP/PS1 control mice. In addition, running-induced improvements in spatial learning and memory were significantly associated with running-induced increases in spinophilin-immunoreactive puncta and neurons numbers in the mPFC. Running exercise could delay the loss of spinophilin-immunoreactive puncta and neurons in the mPFC of APP/PS1 mice. This finding might provide an important structural basis for exercise-induced improvements in the spatial learning and memory abilities of individuals with AD.

Stress-induced myelin damage in the hippocampal formation in a rat model of depression.

BACKGROUND: According to previous studies, myelin damage may be involved in the occurrence of depression. However, to date, no study has quantitatively investigated the changes in myelinated fibers and myelin sheaths in the hippocampal formation (HF) and hippocampal subfields in the context of depression. METHODS: Male Sprague-Dawley (SD) rats (aged 4-5 weeks) were evenly divided into the control group and chronic unpredictable stress (CUS) group. Behavioral tests were performed, and then changes in myelinated fibers and myelin ultrastructure in hippocampal subfields in depression model rats were investigated using modern stereological methods and transmission electron microscopy techniques. RESULTS: After a four-week CUS protocol, CUS rats showed depressive-like and anxiety-like behaviors. The total length and total volume of myelinated fibers were reduced in the CA1 region and DG in the CUS group compared with the control group. The total volumes of myelin sheaths and axons in the CA1 region but not in the DG were significantly lower in the CUS group than in the control group. The decrease in the total length of myelinated nerve fibers in the CA1 region in CUS rats was mainly due to a decrease in the length of myelinated fibers with a myelin sheath thickness of 0.15 µm-0.20 µm. LIMITATIONS: The exact relationship between the degeneration of myelin sheaths and depression-like, anxiety-like behaviors needs to be further investigated. CONCLUSIONS: CUS induces depression- and anxiety-like behaviors, and the demyelination in the CA1 region induced by 4 weeks of CUS might be an important structural basis for these behaviors.

Anti-LINGO-1 antibody treatment alleviates cognitive deficits and promotes maturation of oligodendrocytes in the hippocampus of APP/PS1 mice.

Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 1 (LINGO-1), a negative regulator of oligodendrocyte differentiation and myelination, is associated with cognitive function, and its expression is highly upregulated in Alzheimer's disease (AD) patients. Anti-LINGO-1 antibody treatment can effectively antagonize the negative regulatory effect of LINGO-1. In this study, we aim to assess the effect of anti-LINGO-1 antibody treatment on cognition and hippocampal oligodendrocytes in an AD transgenic animal model. First, 10-month-old male amyloid-ß (Aß) protein precursor (APP)/presenilin 1 (PS1) mice were administered anti-LINGO-1 antibody for 8 weeks. Then, learning and memory abilities were assessed with the Morris water maze (MWM) and Y-maze tests, and Aß deposition and hippocampal oligodendrocytes were investigated by immunohistochemistry, immunofluorescence, and stereology. We found that anti-LINGO-1 antibody alleviated the deficits in spatial learning and memory abilities and working and reference memory abilities, decreased the density of LINGO-1 positive cells, decreased Aß deposition, significantly increased the number of mature oligodendrocytes and the density of myelin, reversed the abnormal increases in the number of oligodendrocyte lineage cells and the densities of oligodendrocytes precursor cells in APP/PS1 mice. Our results provide evidence that LINGO-1 might be involved in the process of oligodendrocyte dysmaturity in the hippocampus of AD mice, and that antagonizing LINGO-1 can alleviate cognitive deficits in APP/PS1 mice and decrease Aß deposition and promote oligodendrocyte differentiation and maturation in the hippocampus of these mice. Our findings suggest that changes in LINGO-1 and oligodendrocytes in the hippocampus play important roles in the pathogenesis of AD and that antagonizing LINGO-1 might be a potential therapeutic strategy for AD.

[Prenatal diagnosis of trisomy 18 syndrome with sonogram index scoring system].

OBJECTIVE: To explore the value of sonogram index scoring system in the prenatal diagnosis of trisomy 18 syndrome. METHODS: Neonates who had prenatal sonographic screening in our tertiary center were followed up from January 2004 to December 2009. The fetuses who were suspected with abnormalities received karyotype analysis. All fetuses were divided into case group (trisomy 18 group) and the control group (non-trisomy 18 group). The latter group was constituted of fetuses with trisomy 21, trisomy 13, other chromosomal abnormalitis and fetuses with normal karyotype. Logistic regression analysis was done to decide the individual sonographic features of trisomy 18. A score was assigned for ultrasound markers according to their likelihood ratios for trisomy 18 syndrome. A score of 3 was assigned for the sonographic features with likelihood ratio over 200, 2 for those with likelihood ratio between 100 and 200, and 1 for those with likelihood ratio less than 100. The diagnostic efficacy of the ultrasound index scoring system was evaluated by diagnostic test. The optimal cutoff value was determined by receiver operating characteristic (ROC) curve. RESULTS: The study group included 59 fetuses with trisomy 18. And 26 486 fetuses did not have trisomy 18 syndrome, including 93 fetuses with trismoy 21, 19 fetuses with trisomy 13, 134 fetuses with other chromosomal abnormalities, 3739 fetuses with normal karyotype and 22 501 fetuses with normal appearance after birth. Two or more structural defects were observed in each trisomy 18 fetus. The highest incidence of sonogram abnormalities was extremities abnormalities (85%, 50/59), followed by cardiac defects (83%, 49/59) and central nervous system (CNS) malformations (75%, 44/59). Overlapping fingers, ventricular septal defect and strawberry-shaped skull were the most common abnormalities in extremities abnormalities, cardiac defects and CNS malformations, respectively. Logistic regression identified 16 markers, including choroid plexus cyst, strawberry-shaped skull, enlarged cisterna magna, holoprosencephaly, low-set ears, ventricular septal defect, hypoplastic left heart syndrome, etc. Different scores were assigned according to the likelihood ratios of these markers. In trisomy 18 group, fetuses with the sonographic score of 1, 4, 9, 10 to 16 were 2% (1/59), 9% (5/59), 10% (6/59) and 32% (19/59) respectively, whereas in non-trisomy 18 group they were 2.549% (675/26 486), 0.215% (57/26 486), 0.004% (1/26 486) and zero, respectively. When a score of 4 was used as the cutoff value for diagnosing fetal trisomy 18, the sensitivity and specificity were 0.966 and 0.997, respectively. The area under ROC curve was 0.999. CONCLUSIONS: The ultrasound index scoring system may help to quantify the ultrasound features and has a good diagnostic value for fetal trisomy 18 syndrome. The cutoff value of 4 has the best diagnostic efficacy.

[Clinical features of abnormal chromosome karyotypes in twin pregnancies complicated with structural abnormalities].

OBJECTIVE: To investigate the clinical features of the abnormal chromosome karyotypes in twin pregnancies complicated with fetal malformations. METHODS: Totally 181 twin pregnancies (362 fetuses) in which one or two fetuses had abnormalities diagnosed by ultrasound were referred to the First Affiliated Hospital of Sun Yat-Sen University from January, 2000 to September, 2010. They were divided into different groups according to (1) maternal age: the cases with maternal age ≥ 35 were divided into advanced pregnancy group (105 fetuses), and those with maternal age < 35 were divided into young pregnancy group (203 fetuses); (2) conceived method: those conceived by assisted reproductive technology were divided into assisted reproductive group (81 fetuses), and the natural conception pregnancies were divided into natural conception group (227 fetuses); (3) chorionicity: the monochorionic twin (MCT) pregnancies were divided into MCT group (123 fetuses), and the dichorionic twin (DCT) pregnancies were divided into DCT group (185 fetuses); (4) structural abnormalities: 205 fetuses with structural abnormalities were divided into the abnormal fetal group, and 103 fetuses without structural abnormalities were divided into the normal fetal group. All fetuses were examined by the ultrasound and chromosomes were examined in 308 fetuses. RESULTS: (1) The karyotype of fetuses: among 181 twin pregnancies, 23 cases had chromosomal abnormalities in 1 or 2 fetuses (12.7%, 23/181), and chromosomes were examined in both fetuses in 20 of 23 cases. Twenty-six of 308 fetuses were found with abnormal chromosomes (8.4%, 26/308), and the aneuploid was the most common type of abnormal karyotypes (53.8%, 14/26). Twenty-one of 205 fetuses with malformations were found with abnormal karyotypes (10.2%, 21/205). (2) Seven of 123 fetuses in MCT group were with abnormal karyotypes (5.7%, 7/123), and 19 of 185 fetuses in DCT group were with abnormal karyotypes (10.3%, 19/185). There was no statistical difference of abnormal chromosome incidence between the two groups. There were 14 fetuses with aneuploid in DCT group (7.6%, 14/185); but there was no fetus with aneuploid in MCT group. There was statistical difference between these two groups. In two cases of DCT group, only one fetus with malformation received chromosome examination because another fetus was dead, and the karyotypes were trisomy 21 and trisomy 18 respectively. Both fetuses of the rest 17 cases received chromosome examination, and the chromosomes of both fetuses in each pregnancy were different. Fifteen of 19 fetuses with abnormal chromosomes in DCT group were complicated with structural abnormalities, and 7 fetuses of 4 twin pregnancies in MCT group were with chromosomal abnormalities. (3) The comparison of the abnormal karyotype incidence between the advanced pregnancy group and young pregnancy group: the abnormal karyotype incidence of the advanced pregnancy group was 7.6% (8/105), and that was 8.9% (18/203) in young pregnancy group. There was no statistical difference between the two groups (P > 0.05). Six of 105 fetuses in advanced pregnancy group were aneuploids (5.7%, 6/105), and 8 of 203 fetuses in young pregnancy group were aneuploids (3.9%, 8/203). The aneuploid incidence in advanced pregnancy group was significantly higher than that in young pregnancy group (P < 0.05).(4) The comparison of the abnormal karyotype incidence between the assisted reproductive group and the natural conception group: 11 of 81 fetuses were with the abnormal karyotypes in assisted reproductive group (13.6%, 11/81), and 15 of 227 fetuses were with the abnormal karyotypes in assisted reproductive group (6.6%, 15/227). There was statistical difference between the two groups (P < 0.05). There were 7 fetuses with the aneuploid in assisted reproductive group (8.6%, 7/81) and 7 fetuses with the aneuploid in natural conception group (3.1%, 7/227), which showed no statistical difference (P > 0.05). (5) The comparison of the abnormal karyotype incidence between the abnormal fetal group and normal fetal group: 21 of 205 fetuses in abnormal fetal group were with abnormal karyotypes (10.2%, 21/205), and 5 of 103 fetuses in normal fetal group were with abnormal karyotypes (4.9%, 5/103). There was no statistical difference (P > 0.05). 13 fetuses in abnormal fetal group were with the aneuploid (6.3%, 13/205), and only one fetus in normal fetal group was aneuploid (1.0%, 1/103). There was statistical difference between the two groups (P < 0.05). CONCLUSIONS: Aneuploid is the most common abnormal karyotype in twin pregnancy complicated with fetal abnormalities, especially trisomy 21. Aneuploid mainly occurs in only one fetus of DCT, and chromosomal discordance is usually found in DCT. While in MCT, the twin fetuses with the same abnormal karyotype may have different phenotypes. The results suggest that it is necessary to analyze both karyotypes of twins even if only one fetus is complicated with structural abnormalities.

Anti-Lingo-1 antibody ameliorates spatial memory and synapse loss induced by chronic stress.

Chronic stress can induce cognitive impairment, and synapse number was significantly decreased in the hippocampus of rats suffering from chronic stress. Lingo-1 is a potent negative regulator of axonal outgrowth and synaptic plasticity. In the current study, the effects of anti-Lingo-1 antibody on the spatial learning and memory abilities and hippocampal synapses of stressed rats were investigated. After 4 weeks of stress exposure, the model group was randomly divided into a chronic stress group and an anti-Lingo-1 group. Then, the anti-Lingo-1 group rats were treated with anti-Lingo-1 antibody (8 mg/kg) for 3 weeks. The effects of anti-Lingo-1 antibody on the spatial learning and memory abilities were investigated with the Morris water maze test. Immunohistological staining and an unbiased stereological method were used to estimate the total number of dendritic spine synapses in the hippocampus. At the behavioral level, after 3 weeks of treatment, the anti-Lingo-1 group rats displayed significantly more platform location crossings in the Morris water maze test than the chronic stress group rats. Anti-Lingo-1 significantly prevented the declines in dendritic spine synapses and postsynaptic density protein-95 (PSD-95) expression in the dentate gyrus and the CA1 and CA3 regions of the hippocampus. The present results indicated that anti-Lingo-1 antibody may be a safe and effective drug for alleviating memory impairment in rats after chronic stress and protecting synapses in the hippocampus of stressed rats.

Exercise improves depressive symptoms by increasing the number of excitatory synapses in the hippocampus of CUS-Induced depression model rats.

Exercise has been considered for the treatment of depression, but the mechanism by which exercise improves depression is still unclear. To clarify the mechanism, rats were randomly divided into the control, chronic unpredictable stress (CUS)/standard and CUS/running groups. The rats in the CUS/running group ran for four weeks. In this study, a sucrose preference test (SPT) was used to evaluate the depression-like symptoms in the rats, and western blot, immunohistochemical and stereological analyses were performed to study the expression of synaptic-related proteins in the hippocampus and the changes in excitatory synapses in each sub-region. The results show that sucrose preference in the CUS/standard group was significantly lower than that in the control group, but in the CUS/running group, sucrose preference was higher than that in the CUS/standard group. Surprisingly, there was no difference in the synaptic-related proteins in the hippocampus among groups. The CUS/standard group exhibited fewer spinophilin+ (Sp+) dendritic spines representing excitatory synapses in CA1, CA3 and dentate gyrus (DG) of the hippocampus than the control group, whereas the CUS/running group exhibited significantly more Sp+ dendritic spines in these regions than the CUS/standard group, indicating that excitatory synapses were reduced in depressed rats and that running exercises could reverse this change. We hypothesize that the changes in the number of excitatory synapses better reflect the changes in depressive symptoms than the level of synaptic proteins and that the effect of exercise on excitatory synapses in the sub-regions of the hippocampus may be an important structural indicator of the improvement of depressive symptoms.

Changes in white matter and the effects of fluoxetine on such changes in the CUS rat model of depression.

OBJECTIVE: To explore the pathogenesis of depression and the possible mechanism of the effects of selective serotonin reuptake inhibitors (SSRIs) on the myelinated fibers and myelin sheaths in the white matter during the antidepressant action of fluoxetine. METHODS: In this study, Sprague Dawley (SD) rats were divided into a Control group, a group treated with CUS and no drugs (CUS/Standard group) and a group treated with CUS and fluoxetine (CUS/FLX group). The CUS/FLX group was treated with fluoxetine at dose of 5 mg/kg for 21 days. The white matter volume, the myelinated fiber parameters and the myelin sheath volume in the white matter were calculated from transmission electron microscope images through unbiased stereological methods. RESULTS: The total volume and total length of myelinated fibers;and mean volume of white matter of the CUS/Standard group were significantly decreased compared to values from the control group (p = 0.025, p = 0.007, p = 0.000), whereas no significant differences in these stereological parameters were found between the CUS/Standard and CUS/FLX groups (p > 0.05). CONCLUSIONS: Fluoxetine successfully treated depression-like behavior but had no effects on the white matter or its component myelinated fibers in the CUS rat model of depression.

[Comparison between transabdominal and transcervical chorionic villus sampling in clinical application for prenatal diagnosis].

OBJECTIVE: To compare transabdominal and transcervical chorionic villus sampling (TC-CVS) in application for prenatal diagnosis, and to summarize the experience of transabdominal chorionic villus sampling (TA-CVS). METHODS: One hundred and nine TA-CVS between April 2005 and November 2007 and 69 TC-CVS between August 1999 and March 2005 were retrospectively analyzed. RESULTS: (1) The mean gestational age was (12.4 +/- 1.9) weeks at TA-CVS and (8.8 +/- 1.2) weeks at TC-CVS (P < 0.01). (2) Compared with TC-CVS, punctures were fewer (1.4 +/- 0.5) and (1.1 +/- 0.4) and specimen amount was more (9 +/- 5) mg and (17 +/- 5) mg in TA-CVS, and the success rate of one puncture (62.3% vs 87.2%) was higher in TA-CVS. (3) Among the cases followed up, the incidence of vaginal bleeding (TA-CVS: 2 cases, 2.0%; TC-CVS: 2 cases, 6.1%) and spontaneous abortion (TA-CVS: 4 cases, 4.0%; TC-CVS: 1 cases, 3.0%) were not significantly different between the two groups (P > 0.05). CONCLUSION: TA-CVS appears to be a good method for early prenatal diagnosis with a wide range of indications, high success rate and sufficient specimen.

[Bipolar coagulation used in selective feticide of monochorionic twins with one twin anomaly].

OBJECTIVE: To summarize our preliminary experience of selective feticide with bipolar coagulation in complicated monochorionic twins (MCT), and discuss the clinical application of feticide in discordant MCT. METHODS: Three MCT with one twin anomaly, in which 2 had severe twin-twin transfusion syndrome (TTTS), stage IV, and 1 had acardiac twin, were identified in the second trimester of pregnancy. To terminate the abnormal twin and isolate the co-twin's circulation completely, selective feticide was performed by umbilical cord occlusion with bipolar coagulation under guidance of ultrasound and fetoscopy. After each invasive procedure, serial monitoring was performed, including procedural complications, Doppler of fetal middle cerebral artery and umbilical artery. Pregnancies were followed up every 2 weeks for fetal growth until delivery. After birth the placentas and the terminated fetuses were examined. RESULT: Cord occlusion was successfully accomplished in all 3 targeted fetuses, at 21, 22 and 24 weeks of gestation respectively. One case with TTTS was complicated with rupture of the membrane in the terminated fetus the 7th day after the procedure, and a healthy baby was born at 32 weeks. The other case with TTTS delivered a boy by cesarean section at 38 weeks. The third case with TRAP is at 35 weeks of gestations and under regular follow-up. Monochorionicity was confirmed by placental examination after delivery, and the effects of bipolar coagulation were observed at the cord of terminated fetuses. CONCLUSIONS: Umbilical cord occlusion with bipolar coagulation is an effective procedure for selective feticide in MCT with one twin anomaly. The outcome of normal fetus can be favorable.

Sex Differences in the White Matter and Myelinated Fibers of APP/PS1 Mice and the Effects of Running Exercise on the Sex Differences of AD Mice.

Previous studies have suggested that changes in the white matter might play an important role in the pathogenic processes of Alzheimer's disease (AD). However, no study has investigated sex differences in these changes. Previous studies found that running exercise could delay both the decline in spatial learning and memory abilities as well as the changes in the white matter during early AD in male mice. However, whether exercise also has an effect on the changes in the white matter in female AD mice remains unknown. To address these questions, 6- and 10-month-old male and female APP/PS1 double transgenic AD mice were used. The 6-month-old male and female APP/PS1 double transgenic AD mice underwent a 4-month running exercise regime. The white matter volume and parameters of the myelinated fibers in the white matter of the 10-month-old exercised and non-exercised male and female AD mice were investigated using electron microscopy and stereological methods. There were no significant differences in the mean escape latencies between the male and female AD mice in the non-exercised groups, but after 4 months of treadmill exercise, the mean escape latencies of the female exercised AD mice had significantly shortened compared with those of the male exercised AD mice. The total white matter volume and most of the parameters of the myelinated fibers of the white matter in the female AD mice were significantly lower than those of the male AD mice. The total length of the myelinated fibers with diameters ranging from 0.6 to 0.7 µm, the axonal diameter of the myelinated fibers and the g-ratio of the myelinated fibers in the white matter of the exercised female AD mice were significantly increased compared with those of the non-exercised female AD mice. There were sex-specific differences in the white matter and myelinated fibers of white matter in the AD mice. Running exercise more effectively delayed the decline in spatial learning and memory abilities and delayed the changes in the myelinated fibers of the white matter in female transgenic mice with early AD than in male transgenic mice.

Running exercise protects against myelin breakdown in the absence of neurogenesis in the hippocampus of AD mice.

Neurogenesis might influence oligodendrogenesis and selectively instruct myelination in the mammalian brain. Running exercise could induce neurogenesis and protect the myelin sheaths in the dentate gyrus of AD mice. It is unclear whether running exercise can protect myelin sheaths in the absence of neurogenesis in the hippocampus of AD mice. Six-month-old male APP/PS1 transgenic mice were randomly assigned to a control group (Tg control) or a running group (Tg runner), and age-matched non-transgenic littermates were used as a wild-type group (WT control). The Tg runner mice were subjected to a running protocol for four months. The behaviors of the mice in the three groups were then assessed using the Morris water maze, and related quantitative parameters of the myelin sheaths within the CA1 field were investigated using unbiased stereological and electron microscopy techniques. Learning and spatial memory performance, CA1 volume, the volumes of the myelinated fibers, and myelin sheaths in the CA1 field were all significantly worse in the Tg control mice than in the WT control mice. Learning and spatial memory performance, CA1 volume and the volume of the myelin sheaths in the CA1 field were all significantly greater in the Tg runner mice than in the Tg control mice. These results reveal demyelinating lesions in the CA1 field of Alzheimer's disease (AD) mice and indicate that running exercise could protect against myelin sheath degeneration in the absence of neurogenesis, thereby reducing CA1 atrophy and delaying the onset and progression of AD.