The Memory Orchestra: Contribution of Astrocytes / 神经科学通报·英文版

For decades, memory research has centered on the role of neurons, which do not function in isolation. However, astrocytes play important roles in regulating neuronal recruitment and function at the local and network levels, forming the basis for information processing as well as memory formation and storage. In this review, we discuss the role of astrocytes in memory functions and their cellular underpinnings at multiple time points. We summarize important breakthroughs and controversies in the field as well as potential avenues to further illuminate the role of astrocytes in memory processes.

The ATP Level in the mPFC Mediates the Antidepressant Effect of Calorie Restriction / 神经科学通报·英文版

Food deprivation can rescue obesity and overweight-induced mood disorders, and promote mood performance in normal subjects. Animal studies and clinical research have revealed the antidepressant-like effect of calorie restriction, but little is known about the mechanism of calorie restriction-induced mood modification. Previous studies have found that astrocytes modulate depressive-like behaviors. Inositol 1,4,5-trisphosphate receptor type 2 (IP3R2) is the predominant isoform in mediating astrocyte Ca

The ATP Level in the mPFC Mediates the Antidepressant Effect of Calorie Restriction / 神经科学通报·英文版

Food deprivation can rescue obesity and overweight-induced mood disorders, and promote mood performance in normal subjects. Animal studies and clinical research have revealed the antidepressant-like effect of calorie restriction, but little is known about the mechanism of calorie restriction-induced mood modification. Previous studies have found that astrocytes modulate depressive-like behaviors. Inositol 1,4,5-trisphosphate receptor type 2 (IP3R2) is the predominant isoform in mediating astrocyte Ca

Expression Patterns of Inducible Cre Recombinase Driven by Differential Astrocyte-Specific Promoters in Transgenic Mouse Lines / 神经科学通报·英文版

Astrocytes are the most abundant cell type in the central nervous system (CNS). They provide trophic support for neurons, modulate synaptic transmission and plasticity, and contribute to neuronal dysfunction. Many transgenic mouse lines have been generated to obtain astrocyte-specific expression of inducible Cre recombinase for functional studies; however, the expression patterns of inducible Cre recombinase in these lines have not been systematically characterized. We generated a new astrocyte-specific Aldh1l1-CreER knock-in mouse line and compared the expression pattern of Cre recombinase between this and five widely-used transgenic lines (hGfap-CreER from The Jackson Laboratory and The Mutant Mouse Resource and Research Center, Glast-CreER, Cx30-CreER, and Fgfr3-iCreER) by crossing with Ai14 mice, which express tdTomato fluorescence following Cre-mediated recombination. In adult Aldh1l1-CreER:Ai14 transgenic mice, tdTomato was detected throughout the CNS, and five novel morphologically-defined types of astrocyte were described. Among the six evaluated lines, the specificity of Cre-mediated recombination was highest when driven by Aldh1l1 and lowest when driven by hGfap; in the latter mice, co-staining between tdTomato and NeuN was observed in the hippocampus and cortex. Notably, evident leakage was noted in Fgfr3-iCreER mice, and the expression level of tdTomato was low in the thalamus when Cre recombinase expression was driven by Glast and in the capsular part of the central amygdaloid nucleus when driven by Cx30. Furthermore, tdTomato was clearly expressed in peripheral organs in four of the lines. Our results emphasize that the astrocyte-specific CreER transgenic lines used in functional studies should be carefully selected.

Astrocytic GABA Receptors in Mouse Hippocampus Control Responses to Behavioral Challenges through Astrocytic BDNF / 神经科学通报·英文版

Major depressive disorder (MDD) is a common mood disorder that affects almost 20% of the global population. In addition, much evidence has implicated altered function of the gamma-aminobutyric acid (GABAergic) system in the pathophysiology of depression. Recent research has indicated that GABA receptors (GABARs) are an emerging therapeutic target in the treatment of stress-related disorders such as MDD. However, which cell types with GABARs are involved in this process is unknown. As hippocampal dysfunction is implicated in MDD, we knocked down GABARs in the hippocampus and found that knocking down these receptors in astrocytes, but not in GABAergic or pyramidal neurons, caused a decrease in immobility in the forced swimming test (FST) without affecting other anxiety- and depression-related behaviors. We also generated astrocyte-specific GABAR-knockout mice and found decreased immobility in the FST in these mice. Furthermore, the conditional knockout of GABARs in astrocytes selectively increased the levels of brain-derived neurotrophic factor protein in hippocampal astrocytes, which controlled the decrease in immobility in the FST. Taken together, our findings contribute to the current understanding of which cell types expressing GABARs modulate antidepressant activity in the FST, and they may provide new insights into the pathological mechanisms and potential targets for the treatment of depression.

Recent progress in neurobiological mechanisms of depression / 生理学报

Revealing the neurobiological mechanism of depression has always been a big challenge in the field of neuroscience. Not only are depressive syndromes heterogeneous and their aetiologies diverse, but also some symptoms are impossible to reproduce in animal models. Nevertheless, great progress has been made on the understanding and treatment of depression in recent years. In this review, we focus on key leading hypotheses in the neurobiological mechanism of depression, examine their strengths and weaknesses critically, and also highlight new insights that promise to extend the understanding of depression and its treatment.

Construction and identification of a RNA interference plasmid for rat BNIP3 gene / 南方医科大学学报

<p><b>OBJECTIVE</b>To construct a RNA interfering plasmid targeting rat Bcl-2/E1B-19K-interacting protein 3 (BNIP3) and assess its effect on exogenous BNIP3 expression in HEK293 cells.</p><p><b>METHODS</b>The miRNA sequences were designed using Invitrogen BLOCK-iT RNAi Designer and synthesized into double-strand oligonucleotides, which were cloned into the pcDNATM6.2-GW/EmGFP-miR vector, followed by transformation of the product into competent Top10 E. coli cells. After expansion of the transformed bacteria, the plasmid was extracted and sequenced before its co-transfection with pEGFP-C3- rBNIP3 plasmid into HEK293 cells. The interference effect of the constructed plasmid on BNIP3 mRNA and protein expression were detected by real-time PCR and Western blotting.</p><p><b>RESULTS</b>The sequencing result indicated that the interfering plasmid targeting rat BNIP3 was constructed correctly. After transfection into HEK293 cells, the interfering plasmid significantly inhibited exogenous BNIP3 mRNA and protein expressions.</p><p><b>CONCLUSION</b>The RNA interfering plasmid targeting rat BNIP3 has been constructed successfully, which provides a useful tool for studying the function of BNIP3.</p>

Neuregulin-1 temperature-dependently inhibits the long-term potentiation in the CA1 region in mouse hippocampal slices / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of neurogulin-1 (NRG1) on the transmission and plasticity of CA1 synapses in mouse hippocampal slices at different temperatures.</p><p><b>METHODS</b>Under room temperature (26-/+1 degrees C) or physiological temperature (32-/+1 degrees C), field excitatory postsynaptic potential (fEPSP) evoked by extracellular microelectrode recording technique was recorded in the CA1 region in adult mouse hippocampal slices, and the long-term potentiation (LTP) was induced by high frequency stimulation (HFS). The effects of NRG1 on the baseline fEPSP and induction of LTP in CA1 region were observed.</p><p><b>RESULTS</b>No significant variation in the slope of fEPSP relative to the baseline fEPSP was observed after perfusion with NRG1 at room temperature or physiological temperature (P > 0.05). After HFS at the room temperature, the mean slope of fEPSP in the slices perfused with NRG1 was similar to that of the control group (P > 0.05), but HFS at the physiological temperature resulted in significant reduction in the mean slope of fEPSP in the slices perfused with NRG1 (P < 0.01).</p><p><b>CONCLUSION</b>NRG1 may temperature-dependently inhibit the induction of LTP in the CA1 region in mouse hippocampal slices.</p>

Strychnos alkaloids inhibit the proliferation of adult rat neuroprogenitor cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the effects of strychnos alkaloids on the proliferation of adult rat neuroprogenitor cells.</p><p><b>METHODS</b>Strychnos alkaloids free of strychnine and brucine were extracted from Strychnos nux vomica, and the effects of Strychnos alkaloids on the survival of HEK293 and PC12 cells were evaluated using MTT assay. In vitro cultured adult rat neuroprogenitor cells isolated from the hippocampus were treated with different concentrations of Strychnos alkaloids for 2 days, and the cell proliferation was assessed using BrdU incorporation assay.</p><p><b>RESULTS</b>At the concentration above 0.5 mg/ml, Strychnos alkaloids produced toxic effect against HEK293 cells (P<0.0001), while for PC12 cells, Strychnos alkaloids inhibited the cell survival at the concentration as low as 5 microg/ml (P<0.0001). After 2 days of exposure to 50 microg/ml Strychnos alkaloids, the neuroprogenitor cells showed significantly decreased number of BrdU-positive cells (P<0.01), but the total cell number remained stable when compared with that of the control cells (P>0.05), whereas at the concentration of 100 microg/ml, Strychnos alkaloids produced obvious cytotoxicity against the neuroprogenitor cells.</p><p><b>CONCLUSION</b>Strychnos alkaloids can significantly inhibit the proliferation of adult rat neuroprogenitor cells, and this effect is probably selective, suggesting the potential of Strychnos alkaloids as a new drug for treatment of neurocytoma.</p>

Progressive studies of paeoniflorin / 中国中药杂志

Paeoniflorin is one of the bioactive components of Paeonia lactiflora, a traditional Chinese herbal medicine. It is the main monoterpene glucoside isolated from the P. lactiflora in 1963. Since then, researchers have found that paeoniflorin has multifold pharmacological effects. In this review, based on the recent available papers published in PubMed and National Knowledge Infrastructure Data Base, we present the major current approaches in understanding the detection methodology, pharmacokinetics and pharmacology, and toxicology of paeoniflorin.

Developmental changes in synaptic and extrasynaptic N-methyl-D-aspartate receptors in cultured rat hippocampal neurons / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate changes in synaptic and extrasynaptic N-methyl-D-aspartate receptors (NMDAR) during the development of cultured rat hippocampal neurons.</p><p><b>METHODS</b>Synaptic and extrasynaptic NMDAR channel currents were recorded from 1-day-old rat hippocampal neurons cultured for 1 and 2 weeks with patch-clamp technique in whole-cell configuration and outside-out configuration, respectively.</p><p><b>RESULTS</b>The amplitude of NMDAR-mediated miniature excited postsynaptic current (Meps(CNMDA)) decreased in neurons cultured for 2 weeks as compared with that recorded in neurons cultured for 1 week, and the 2-week neurons showed also much lowered sensitivity to selective NR2B blocker ifenprodil. The amplitude and open probability of extrasynaptic NMDAR in the 2-week neurons were significantly higher than those in the 1-week neurons, but the neurons differred little in conduction and reverse potential. Ifenprodil decreased the high conductance and open probability in both neurons, but the effect was more potent in the 2-week ones.</p><p><b>CONCLUSIONS</b>There can be developmental changes in synaptic and extrasynaptic NMDAR channel currents in cultured rat hippocampal neurons, indicating that different NMDAR subtypes are expressed in the synaptic and extrasynaptic regions during the development of the hippocampal neurons. In 1-week neurons, NR2B are predominant both in synaptic and extrasynaptic regions, and at 2 weeks, synaptic NR2B are replaced by NR2A but NR2B still remains the predominant subtypes outside the synapses.</p>

Periodic quantity variation of proliferating neuronal progenitors in adult rats after global brain ischemia / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the periodic quantity variation of proliferating neuronal progenitors after global brain ischemia and provide evidence for choosing the time-window of drug therapy to promote neuronal regeneration after ischemia.</p><p><b>METHODS</b>Adult male Wistar rats were subjected to 15-min global brain ischemia (four-vessel occlusion model) and randomized subsequently into 8 groups (n=3). The rats were given intraperitoneal injections of BrdU (75 mg/kg) for 4 times daily (at a 2-hour interval) since day 7 till day 11 after ischemia, and on day 29, the rats were perfused transcardially for fixation. Another 3 normal rats were given BrdU in the same manner and killed the next day. Coronal sections of the brain tissue (30 microm) were prepared for immunocytochemical detection of BrdU-labeled cells and immunofluorescent detection of BrdU/NeuN double-labeled cells. The density of BrdU-positive cells and BrdU/NeuN double-labeled cells in the hippocampal dentate gyrus (DG) and CA1 region were counted and the density of proliferating cells at different days after ischemia were compared using one-way ANOVA.</p><p><b>RESULTS</b>The proliferation of the neuronal progenitors increased after global brain ischemia. The number of BrdU-positive cells in the DG and CA1 region decreased gradually in 7-10 days after ischemia, and reached the normal level during 11-14 days. The differentiation of the progenitors did not vary after ischemia.</p><p><b>CONCLUSION</b>Increased proliferation of the neuroprogenitors occurs mainly within the initial 10 days after global ischemia in rats.</p>

Neuroprotection of chloride channel blockers against NMDA-induced apoptosis of cultured rat hippocampal neurons / 南方医科大学学报

Activation of N-methyl-d-aspartic acid (NMDA) receptor plays an important role in neuronal apoptosis induced by cerebral ischemia but the underlying mechanisms are still unclear. The present study examined the neuroprotection of three chloride blockers in an in vitro cell model of cerebral ischemia established by treatment of cultured rat hippocampal neurons with NMDA. Hoechst 33258 staining and MTT assay were used to detect neuronal apoptosis and cell viability, respectively. The neuroprotective effects of chloride channel blockers on the cell viability and neuronal apoptosis were only observed when the blockers were applied before NMDA exposure. In comparison with DIDS, SITS showed more potent protective effect in a dose-dependent manner, whereas NPPB showed no significant neuroprotective effect. The results demonstrate that pretreatment with both SITS and DIDS have protective effect against neuronal apoptosis, which is achieved by blocking both NMDA receptor and chloride channel.

An improved method for acute isolation of neurons from the hippocampus of adult rats suitable for patch-clamping study / 生理学报

An improved method is described for fast and reliable isolation of neurons from hippocampus of adult rats by a combination of mechanical and enzymatic means. The procedure allows the isolation of neurons from 500-600-d-old rats (over 300 g), preserving the proximal dendritic structure without impairing the electrical characteristics of the cells. Morphologically distinct neurons can be recognized. Using cell-attached, inside-out and whole-cell configurations of patch clamp technique, it was shown that the enzymatically isolated neurons in hippocampus from rats weighing more than 300 g exhibited voltage-gated calcium, sodium and potassium currents, outwardly rectifying chloride channel and large conductance Ca(2+)-activated potassium channel currents. Approximately, 95% of healthy cells allowed the formation of giga-ohm seals.

Clinical outcome of patients with follicular development retardation by prolonged duration of gonadotropin administration for in vitro fertilization / 中华妇产科杂志

0.05).There were more polycystic ovary (PCO) and (or) polycystic ovarian syndrome (PCOS) patients,more basal antra] follicles,longer duration of Gn stimulation (range 16-33 days),higher Gn dose,lower serum peak estradiol (E_2) level,fewer oocytes,fewer embryos transferred,in group 1 compared with group 2 (P