NRG1 knockdown rescues PV interneuron GABAergic maturation deficits and schizophrenia behaviors in fetal growth restriction mice.

Schizophrenia is a highly debilitating mental disorder, those who experienced fetal growth restriction (FGR) in the early stage of life have a greater probability of schizophrenia. In this study, FGR mice showed hyperactivity in locomotor activity test, sociability dysfunction in three chamber test and nesting social behavior tests, cognition decline in Morris water maze and impaired sensory motor gating function in prepulse inhibition test. Mechanistic studies indicated that the number of parvalbumin (PV) interneuron was significantly reduced in FGR mouse media prefrontal cortex (mPFC). And the mRNA and protein level of neuregulin 1(NRG1), which is a critical schizophrenia gene, increased significantly in FGR mouse mPFC. Furthermore, NRG1 knockdown in FGR mouse mPFC improved PV interneuron GABAergic maturation and rescued schizophrenia behaviors including hyperactivity, social novelty defects, cognition decline, and sensorimotor gating deficits in FGR mice. This study indicates that mPFC NRG1 upregulation is one of the main causes of FGR-induced schizophrenia, which leads to significant reduction of PV interneuron number in mPFC. NRG1 knockdown in mPFC significantly rescues schizophrenia behaviors in FGR mouse. This study thus provides a potential effective therapy target or strategy for schizophrenia patients induced by FGR.

Prediction of central compartment nodal metastases in papillary thyroid cancer using TI-RADS score, blood flow, and multifocality.

BACKGROUND: The relationship between the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) and the risk of lymph node metastases in papillary thyroid cancer (PTC) could improve the detection rate of lymph node metastases in thyroid cancer and provide a scientific basis for clinical diagnosis. PURPOSE: To evaluate the risk of lymph node metastases of PTC associated with the score from ACR TI-RADS adjusted for other correlative factors. MATERIAL AND METHODS: A total of 560 patients with pathologically confirmed PTC were included in the study and classified into a metastases group and a non-metastases group. Clinical and pathological manifestations of the patients were collected. RESULTS: The median TI-RADS score was 13 (p25-p75 = 11-14) among the patients with lymph node metastases, higher than those without metastases 9 (8-10) (P < 0.001). Multiple logistic regression indicated that TI-RADS score (odds ratio [OR] = 2.204), male sex (OR = 2.376), multifocality (OR = 4.170), and rich blood flow (OR = 3.656) were risk factors for lymph node metastases in patients with thyroid carcinoma. Some related factors such as TI-RADS score, age(<45years old), male, multifocality and rich blood flow were related to lymph node metastases in the central area of the neck which could provide therapeutic strategy for further treatment. CONCLUSION: it is not just the TI-RADS score but also multifocality, blood flow, and sex that influence the prediction of the risk of PTC central lymph node metastases.

Fetal growth restriction impairs hippocampal neurogenesis and cognition via Tet1 in offspring.

Fetal growth restriction (FGR) increases the risk for impaired cognitive function later in life. However, the precise mechanisms remain elusive. Using dexamethasone-induced FGR and protein restriction-influenced FGR mouse models, we observe learning and memory deficits in adult FGR offspring. FGR induces decreased hippocampal neurogenesis from the early post-natal period to adulthood by reducing the proliferation of neural stem cells (NSCs). We further find a persistent decrease of Tet1 expression in hippocampal NSCs of FGR mice. Mechanistically, Tet1 downregulation results in hypermethylation of the Dll3 and Notch1 promoters and inhibition of Notch signaling, leading to reduced NSC proliferation. Overexpression of Tet1 activates Notch signaling, offsets the decline in neurogenesis, and enhances learning and memory abilities in FGR offspring. Our data indicate that a long-term decrease in Tet1/Notch signaling in hippocampal NSCs contributes to impaired neurogenesis following FGR and could serve as potential targets for the intervention of FGR-related cognitive disorders.

Sirt7-p21 Signaling Pathway Mediates Glucocorticoid-Induced Inhibition of Mouse Neural Stem Cell Proliferation.

Prenatal glucocorticoid (GC) overexposure impacts fetal hippocampal neural stem cells (NSCs) and increases the risk for relative cognitive and mood disorders in offspring. However, the precise underlying mechanisms remain elusive. Here, we treated mouse hippocampal NSCs with dexamethasone (DEX) in vitro and found that DEX inhibited cell proliferation and Sirt7 expression. In addition, prenatal mouse overexposure to DEX induced the suppression of Sirt7 in the hippocampus of offspring. Sirt7 knockdown significantly decreased the percentage of proliferating cells but did not further reduce the NSC proliferation rate in the presence of DEX, whereas Sirt7 overexpression rescued DEX-induced inhibition of hippocampal NSC proliferation. Moreover, DEX inhibited Sirt7 expression through the glucocorticoid receptor (GR), and p21 was found to mediate the functional effect of DEX-induced Sirt7 suppression. In conclusion, our data demonstrate for the first time the effect of DEX on the Sirt7-p21 pathway in hippocampal NSCs, identifying a new potential therapeutic target for prenatal GC overexposure-related neurodevelopmental disorders in offspring.

MicroRNA-153 improves the neurogenesis of neural stem cells and enhances the cognitive ability of aged mice through the notch signaling pathway.

Aging-related cognitive ability impairments are one of the main threats to public health, and impaired hippocampal neurogenesis is a major cause of cognitive decline during aging. However, the regulation of adult neurogenesis in the hippocampus requires further study. Here, we investigated the role of microRNA-153 (miR-153), a highly conserved microRNA in mice and humans, in adult neurogenesis. During the passaging of neural stem cells (NSCs) in vitro, endogenous miR-153 expression was downregulated, with a decrease in neuronal differentiation ability. In addition, miR-153 overexpression increased the neurogenesis of NSCs. Further studies showed that miR-153 regulated neurogenesis by precisely targeting the Notch signaling pathway through inhibition of Jagged1 and Hey2 translation. In vivo analysis demonstrated that miR-153 expression was decreased in the hippocampi of aged mice with impaired cognitive ability, and that miR-153 overexpression in the hippocampus promoted neurogenesis and markedly increased the cognitive abilities of the aged mice. Overall, our findings revealed that miR-153 affected neurogenesis by regulating the Notch signaling pathway and elucidated the function of miR-153 in aging-related, hippocampus-dependent cognitive ability impairments, and neurodegenerative diseases.

Alfalfa carbon and nitrogen sequestration patterns and effects of temperature and precipitation in three agro-pastoral ecotones of northern China.

Alfalfa (Medicago sativa L.) is a primary and widely cultivated forage crop in China. As a perennial leguminous grass, continuous planted alfalfa may influence carbon and nitrogen sequestration in soils. We evaluated the effect of alfalfa, planted for different lengths of time, and temperature and precipitation on soil organic carbon (SOC) and total nitrogen (TN) contents, and estimated soil SOC and TN inventories from 0-60 cm in three agro-pastoral ecotones of northern China. Alfalfa SOC and TN storage patterns were significantly different with increasing soil depths between the three regions of northern China. Continuous alfalfa grassland planted had a positive effect on accumulation of both SOC and TN in the Northwest region, whereas SOC storage peaked 6-7 years after planting in the Northeast and North region. Moreover, relatively higher TN storage appeared 7 years after planting in the Northeast and North regions. This study controlled as many factors as possible, but we caution that such temporal inferences could be artifacts of site selection. The regression analysis indicated that SOC and TN accumulation was mainly dependent on temperature (≥10°C of effective total accumulated temperature) in the North region. Precipitation in the growing season was the main limiting factor for SOC storage in the Northwest region and TN accumulation in the North regions. Therefore, the different climate factors affecting SOC and TN sequestration in alfalfa occurred at a regional scale.

Impact of grazing on soil carbon and microbial biomass in typical steppe and desert steppe of Inner Mongolia.

The potential of grazing lands to sequester carbon must be understood to develop effective soil conservation measures and sustain livestock production. Our objective was to evaluate the effects of grazing on soil organic carbon (SOC), total nitrogen (TN), microbial biomass carbon (MBC) in Typical steppe and Desert steppe ecosystems, which are both important grassland resources for animal grazing and ecological conservation in China, and to derive region-specific soil C changes associated with different stocking rates (ungrazed, UG; lightly grazed, LG; moderately grazed, MG; heavily grazed, HG). This study substantiated that significant higher SOC, TN and MBC appeared with the treatment of LG in typical steppe. From 2004 to 2010, grazing treatments increased soil carbon storage in desert steppe, which was partly due to the grazing history. The higher MBC concentration and MBC/SOC suggest a great potential for carbon sequestration in the desert steppe ecosystem. The greater MBC in desert steppe than typical steppe was mainly the result of higher precipitation and temperature, instead of soil substrate. The change of MBC and the strong positive relationships between MBC and SOC indicated that MBC in the soil was a sensitive index to indicate the dynamics of soil organic carbon in both steppes in Inner Mongolia of China.