Correlation Analysis of Molecularly-Defined Cortical Interneuron Populations with Morpho-Electric Properties in Layer V of Mouse Neocortex / 神经科学通报·英文版

Cortical interneurons can be categorized into distinct populations based on multiple modalities, including molecular signatures and morpho-electrical (M/E) properties. Recently, many transcriptomic signatures based on single-cell RNA-seq have been identified in cortical interneurons. However, whether different interneuron populations defined by transcriptomic signature expressions correspond to distinct M/E subtypes is still unknown. Here, we applied the Patch-PCR approach to simultaneously obtain the M/E properties and messenger RNA (mRNA) expression of >600 interneurons in layer V of the mouse somatosensory cortex (S1). Subsequently, we identified 11 M/E subtypes, 9 neurochemical cell populations (NCs), and 20 transcriptomic cell populations (TCs) in this cortical lamina. Further analysis revealed that cells in many NCs and TCs comprised several M/E types and were difficult to clearly distinguish morpho-electrically. A similar analysis of layer V interneurons of mouse primary visual cortex (V1) and motor cortex (M1) gave results largely comparable to S1. Comparison between S1, V1, and M1 suggested that, compared to V1, S1 interneurons were morpho-electrically more similar to M1. Our study reveals the presence of substantial M/E variations in cortical interneuron populations defined by molecular expression.

Graded and pan-neural disease phenotypes of Rett Syndrome linked with dosage of functional MeCP2

Rett syndrome (RTT) is a progressive neurodevelopmental disorder, mainly caused by mutations in MeCP2 and currently with no cure. We report here that neurons from R106W MeCP2 RTT human iPSCs as well as human embryonic stem cells after MeCP2 knockdown exhibit consistent and long-lasting impairment in maturation as indicated by impaired action potentials and passive membrane properties as well as reduced soma size and spine density. Moreover, RTT-inherent defects in neuronal maturation could be pan-neuronal and occurred in neurons with both dorsal and ventral forebrain features. Knockdown of MeCP2 led to more severe neuronal deficits as compared to RTT iPSC-derived neurons, which appeared to retain partial function. Strikingly, consistent deficits in nuclear size, dendritic complexity and circuitry-dependent spontaneous postsynaptic currents could only be observed in MeCP2 knockdown neurons but not RTT iPSC-derived neurons. Both neuron-intrinsic and circuitry-dependent deficits of MeCP2-deficient neurons could be fully or partially rescued by re-expression of wild type or T158M MeCP2, strengthening the dosage dependency of MeCP2 on disease phenotypes and also the partial function of the mutant. Our findings thus reveal stable neuronal maturation deficits and unexpectedly, graded sensitivities of neuron-inherent and neural transmission phenotypes towards the extent of MeCP2 deficiency, which is informative for future therapeutic development.

Molecular mechanism of effect of wenban humai granule on stability of atheromatous plaque / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the molecular mechanism of wenban humai granule (WHG) in stabilizing atheromatous plaque, by observing its effect on the collagen degradation and synthesis imbalance manner in the fibrous cap of the plaque.</p><p><b>METHODS</b>Atherosclerosis (AS) rabbit model established by feeding high fat diet. The changes of protein and mRNA expression of macrophage CD68, metalloproteinase-1 (MMP-1), alpha-smooth muscle actin (alpha-SMA) and collagen I (C-I) in model rabbits' neo-genesic intima were determined by immunohistochemical stain and in situ hybridization methods before and after treatment as well as before and after modeling.</p><p><b>RESULTS</b>After being fed with high fat diet for 7 weeks, the protein and mRNA expression of macrophage CD68, MMP-1 in neo-genesic intima of aorta in the model rabbits significantly increased, these changes could be significantly restored after 8 weeks treatment with WHG or simvastatin. At the same time, the expressions of alpha-SMA protein and C-I protein and mRNA slightly increased due to the immigration of SMC in aortic media to neo-genesic intima, these expressions could be further increased after WHG treatment but showed a reducing trend after simvastatin treatment (P < 0.05 and P < 0.01). In the whole course, positive correlation was shown between protein expressions of CD68 and MMP-1 (r = 0.952, P < 0.01) and also between these of alpha-SMA and C-I (r = 0.793, P < 0.01).</p><p><b>CONCLUSION</b>WHG affects the collagen degradation and synthesis imbalance in the fibrous cap of the plaque to stabilize plaque through bi-directional regulation, up-regulating synthesis thesis factors and down-regulating degradation factors, while simvastatin perform its action on plaque stability by down-regulating degradation factors alone.</p>

Study on the relationship between polymorphisms of peroxisome proliferators-activated receptor-gamma coactivator-1alpha gene and type 2 diabetes in Shanghai Hans in China / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To observe the association between single nucleotide polymorphism (SNP) of peroxisome proliferators-activated receptor-gamma coactivator-1alpha (PGC-1alpha ) gene and type 2 diabetes mellitus(T2DM).</p><p><b>METHODS</b>Four common SNPs of PGC-1alpha gene were genotyped with polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and then analyzed with transmission-disequilibrium test (TDT) and sib transmission-disequilibrium test (STDT) in 69 T2DM pedigrees (310 individuals). Furthermore, the authors performed a case-control study to genotype Gly482Ser in 156 patients with T2DM and 111 normal glucose tolerance people without family history.</p><p><b>RESULTS</b>(1)There were no positive results in four variances in TDT-STDT analysis(P> 0.05). (2)The Gly482Ser exhibited a significant difference between the two groups. GA genotype carriers were at increased risk for T2DM (OR=1.85), and there was statistically significant difference in the allele frequency between the case and control groups(P=0.046). (3) The subjects with GG genotype at position Gly482Ser had a higher HDL-C and lower LDL-C and TG levels when compared against those with GA+AA genotype in the control group without family history(P=0.043,lzP=0.046, P=0.037 respectively).</p><p><b>CONCLUSION</b>This study suggested that the PGC-1alpha gene might be implicated in the pathogenesis of T2DM. But the studied SNPs in PGC-1alpha gene may not be major susceptibility ones of T2DM mellitus in Han people of Shanghai.</p>

Role of unsaturated fatty acids in the enhancement of muscarinic current by hyposmotic membrane stretch in guinea pig smooth muscle cells / 生理学报

To investigate the function of exogenous unsaturated fatty acids in hyposmotic membrane stretch enhancement of muscarinic current (ICCh) in antral circular smooth muscle cells of guinea pig, we recorded the membrane current with the conventional whole cell patch-clamp technique. I(CCh) elicited by 50 micromol/L carbachol (CCh) at the holding potential of 20 mV under isosmotic condition was taken as control. Hyposmotic membrane stretch increased I(CCh) to 226.0+/-21.0%. When the cells were pretreated with 5 micromol/L arachidonic acid (AA), linoleic acid (LA) or oleic acid (OA), I(CCh)was inhibited to 3.8+/-0.6%, 35.2+/-0.8% and 66.6+/-0.6% respectively. Hyposmotic membrane stretch increased I(CCh) to 106.0+/-2.5%, 173.2+/-6.8% and 222.1+/-11.0% of the control respectively. Five micromol/L AA inhibited hyposmotic membrane stretch-enhanced I(CCh) by 51.2+/-3.8%, while the control I(CCh) under isosmotic condition was inhibited by 96.2+/-1.6%. The results suggest that unsaturated fatty acids inhibited I(CCh) and the inhibitory effect is more significant when the unsaturation degree is increased. However, the unsaturated fatty acids are not involved in the increase of I(CCh) induced by hyposmotic membrane stretch.

Role of actin microfilament in hyposmotic membrane stretch-induced increase in muscarinic current of guinea-pig gastric myocytes / 生理学报

To investigate the relationship between cytoskeleton and hyposmotic membrane stretch-induced increase in muscarinic current, the role of actin microfilament in hyposmotic membrane stretch-induced increase in muscarinic current was studied with the whole-cell patch clamp technique in guinea-pig gastric myocytes. In this study, the muscarinic current was induced by carbachol (50 micromol/L) or GTPgammaS (0.5 mmol/L). The results showed that hyposmotic superfusate (202 mOsmol/L) increased carbachol-induced current (I(CCh)) by 145+/-27% and increased GTPgammaS-induced current by 183+/-30%; but in the presence of cytochalasin-B (Cyt-B, 20 micromol/L), an actin cytoskeleton disruptor, hyposmotic membrane stretch increased I(CCh) by 70+/-6%. However, hyposmotic membrane stretch induced increase in I(CCh) was potentiated to 545+/-81% by phalloidin (20 micromol/L), an actin microfilament stabilizer. The results demonstrated that hyposmotic membrane stretch increased the muscarinic currents induced by carbachol or GTPgammaS and that the actin microfilament is involved in the process in guinea-pig gastric myocytes.

Relationship between aberrant FHIT transcripts and hepatocellular carcinoma / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the relationship between aberrant FHIT transcripts and hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>Reverse transcription-polymerase chain reaction (RT-PCR) and single strand conformational polymorphism (SSCP) assays were used to analyze the transcripts and mutations of FHIT gene in 24 matched tumorous tissues and para-tumorous tissues from patients with HCC and in 4 normal liver tissues.</p><p><b>RESULTS</b>Aberrant FHIT transcripts were observed in 11 out of 24 (46%) tumorous tissues and in 2 (8%) of the matched para-tumorous tissues.</p><p><b>CONCLUSION</b>FHIT aberrant transcripts may play an important role in the pathogenesis of hepatocellular carcinoma.</p>