Bao-Ming Li

Excess extracellular glutamate leads to excitotoxicity, which induces neuronal death through the overactivation of N-methyl-D-aspartate receptors (NMDARs). Excitotoxicity is thought to be closely related to various acute and chronic neurological disorders, such as stroke and Alzheimer’s disease. Polygalasaponin F (PGSF) is a triterpenoid saponin monomer that can be isolated from Polygala japonica, and has been reported to protect cells against apoptosis. To investigate the mechanisms underlying the neuroprotective effects of PGSF against glutamate-induced cytotoxicity, PGSF-pretreated hippocampal neurons were exposed to glutamate for 24 hours. The results demonstrated that PGSF inhibited glutamate-induced hippocampal neuron death in a concentration-dependent manner and reduced glutamate-induced Ca²⁺ overload in the cultured neurons. In addition, PGSF partially blocked the excess activity of NMDARs, inhibited both the downregulation of NMDAR subunit NR2A expression and the upregulation of NMDAR subunit NR2B expression, and upregulated the expression of phosphorylated cyclic adenosine monophosphate-responsive element-binding protein and brain-derived neurotrophic factor. These findings suggest that PGSF protects cultured hippocampal neurons against glutamate-induced cytotoxicity by regulating NMDARs. The study was approved by the Institutional Animal Care Committee of Nanchang University (approval No. 2017-0006) on December 29, 2017.

Counting ability is one of the many aspects of animal cognition and has enjoyed great interest over the last couple of decades. The impetus for studying counting ability in nonhuman animals has likely come from more than a general interest in animal cognition, as the analysis of animal abilities amplifies our understanding of human cognition. In addition, a model animal with the ability to count could be used to replace human subjects in related studies. Here we designed a behavioral paradigm to train rhesus monkeys to count 1-to-6 visual patterns presented sequentially with long and irregular interpattern intervals on a touch screen. The monkeys were required to make a response to the sixth pattern exclusively, inhibiting response to any patterns appearing at other ordinal positions. All stimulus patterns were of the same size, color, location, and shape to prevent monkeys making the right choice due to non-number physical cues. In the long delay period, the monkey had to enumerate how many patterns had been presented sequentially and had to remember in which ordinal position the current pattern was located. Otherwise, it was impossible for them to know which pattern was the target one. The results show that all three monkeys learned to correctly choose the sixth pattern within 3 months. This study provides convincing behavioral evidence that rhesus monkeys may have the capacity to count.

Background. Intestinal microorganisms play an important role in regulating the neurodevelopment and the brain functions of the host through the gut-brain axis. Lactobacillus, one of the most representative intestinal probiotics, produces important effects on human physiological functions. Our previous studies reveal that the Lactobacillus plantarum WLPL04 has a series of beneficial actions, such as antiadhesion of pathogens, protection from the harmful effect of sodium dodecyl sulfate, and anti-inflammatory stress on Caco2 cells. However, its effects on brain functions remain unknown. The present study aims to evaluate the potential effect of L. plantarum WLPL04 on anxiety/depressive-like behaviors in chronically restrained mice. Methods. Newly weaned mice were exposed to chronic restraint stress for four weeks and raised daily with or without L. plantarum WLPL04 water supplement. Animals were behaviorally assessed for anxiety/depression and cognitive functions. The 16S rRNA sequencing was performed to analyze the intestinal microbiota structure. The levels of the medial prefrontal cortical (mPFC) brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) and serum 5-hydroxytryptamine (5-HT) were examined using Western blot and enzyme-linked immunosorbent assay. Results. The chronic stress-induced anxiety/depressive-like behaviors and cognitive deficits were significantly alleviated by the L. plantarum WLPL04 treatment. The 16S rRNA sequencing analysis showed that the chronic stress reduced the diversity and the richness of intestinal microbiota, which were rescued by the L. plantarum WLPL04 treatment. The levels of BDNF and TrkB in the mPFC and the concentration of 5-HT in the serum remained unchanged in chronically restrained mice treated with the L. plantarum WLPL04. Conclusions. The L. plantarum WLPL04 can rescue anxiety/depressive-like behaviors and cognitive dysfunctions, reverse the abnormal change in intestinal microbiota, and alleviate the reduced levels of 5-HT, BDNF, and TrkB induced by chronic stress in mice, providing an experimental basis for the therapeutic application of L. plantarum on anxiety/depression.

Targeted cell ablation is an important strategy for dissecting the function of individual cells within biological tissues. Here we developed an amplified femtosecond laser-coupled two-photon microscopy (AFL-TPM) system that allows instantaneous and targeted ablation of individual cells and real-time monitoring of neuronal network changes in the living mouse cortex. Through precise and iterative control of the laser power and position, individual cells could be ablated by a single femtosecond light pulse with minimum collateral damage. We further show that ablation of individual somatostatin-expressing interneuron increases the activity of nearby neurons in the primary motor cortex during motor learning. Through precise dendrotomy, we reveal that different dendritic branches of layer 5 pyramidal neurons are structurally and functionally independent. By ablating individual cells and their processes in a spatiotemporally specific manner, the AFL-TPM system could serve as an important means for understanding the functions of cells within the complicated neuronal network.

Myelin of the central nervous system exhibits strong plasticity, and skill learning exercise promotes oligodendrogenesis and adaptive myelination. Increasing evidence shows that brain structures and functions are affected by physical activity. However, the impact of voluntary physical activity on central myelination and its underlying mechanism remains unclear. The present study aimed to investigate the effect of voluntary wheel running (VWR) on central oligodendrogenesis and adaptive myelination in mice. Adult C57BL/6 J mice were placed in running wheels and allowed for voluntary running 2 weeks. Myelin levels in the central nervous system were detected using western blotting, qRT-PCR, immunohistochemical staining, and electron microscopy. Oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs) were detected using immunohistochemical staining and 5-bromo-2-deoxyuridine (BrdU) assays. Motor abilities of the animals were examined using open-field, rotarod running, and beam-walking behavioral paradigms. Vital molecules of Wnt signaling were detected, and the involvement of such molecules was verified using in vitro culture of OPCs. Our results showed that VWR significantly enhanced the myelination in the motor cortex. VWR promoted the proliferation and differentiation of OPCs, and the maturation of OLs. The VWR-regulated myelination was associated with the improved motor skill and decreased mRNA level of Wnt3a/9a, whereas stimulation of Wnt signaling pathway with Wnt3a or Wnt9a suppressed OPCs proliferation and differentiation in vitro. The present study demonstrated that physical activity is highly efficient at promoting myelination in the motor cortex, by enhancing the proliferation of OPCs and accelerating the generation of myelin, providing a step forward in understanding the beneficial effects of physical activity on central myelination and its underlying mechanism.

Significance: Dentate gyrus (DG) dysfunction has been implicated in schizophrenia, a disabling psychiatric disorder. However, underlying pathophysiological mechanisms are not clear. We provide evidence that Tmem108, a novel schizophrenia-associated gene, is highly enriched in DG granule neurons. Tmem108 is required for spine development and glutamatergic transmission. Further investigations indicate a critical role of Tmem108 for AMPA receptor expression in postsynaptic compartments. Mutation ofTmem108leads to schizophrenia-related behavioral deficits. These results provide insight into a potential pathophysiological mechanism for DG dysfunction in schizophrenia.