Neuroscience Bulletin

Deng, Li; Song, Shao-Yong; Zhao, Wei-Ming; Meng, Xiao-Wen; Liu, Hong; Zheng, Qing; Peng, Ke; Ji, Fu-Hai

doi: 10.1007/s12264-024-01260-9pmid: 39078595

Sevoflurane induces developmental neurotoxicity in mice; however, the underlying mechanisms remain unclear. Triggering receptor expressed on myeloid cells 2 (TREM2) is essential for microglia-mediated synaptic refinement during the early stages of brain development. We explored the effects of TREM2 on dendritic spine pruning during sevoflurane-induced developmental neurotoxicity in mice. Mice were anaesthetized with sevoflurane on postnatal days 6, 8, and 10. Behavioral performance was assessed using the open field test and Morris water maze test. Genetic knockdown of TREM2 and overexpression of TREM2 by stereotaxic injection were used for mechanistic experiments. Western blotting, immunofluorescence, electron microscopy, three-dimensional reconstruction, Golgi staining, and whole-cell patch-clamp recordings were performed. Sevoflurane exposures upregulated the protein expression of TREM2, increased microglia-mediated pruning of dendritic spines, and reduced synaptic multiplicity and excitability of CA1 neurons. TREM2 genetic knockdown significantly decreased dendritic spine pruning, and partially aggravated neuronal morphological abnormalities and cognitive impairments in sevoflurane-treated mice. In contrast, TREM2 overexpression enhanced microglia-mediated pruning of dendritic spines and rescued neuronal morphological abnormalities and cognitive dysfunction. TREM2 exerts a protective role against neurocognitive impairments in mice after neonatal exposures to sevoflurane by enhancing microglia-mediated pruning of dendritic spines in CA1 neurons. This provides a potential therapeutic target in the prevention of sevoflurane-induced developmental neurotoxicity.

Lin, Jiezhao; Sun, Yuanfang; Xia, Bin; Wang, Yihan; Xie, Changnan; Wang, Jinfeng; Hu, Jinwei; Zhu, Lixin

doi: 10.1007/s12264-024-01199-xpmid: 38592581

Disruption of the blood-spinal cord barrier (BSCB) is a critical event in the secondary injury following spinal cord injury (SCI). Mertk has been reported to play an important role in regulating inflammation and cytoskeletal dynamics. However, the specific involvement of Mertk in BSCB remains elusive. Here, we demonstrated a distinct role of Mertk in the repair of BSCB. Mertk expression is decreased in endothelial cells following SCI. Overexpression of Mertk upregulated tight junction proteins (TJs), reducing BSCB permeability and subsequently inhibiting inflammation and apoptosis. Ultimately, this led to enhanced neural regeneration and functional recovery. Further experiments revealed that the RhoA/Rock1/P-MLC pathway plays a key role in the effects of Mertk. These findings highlight the role of Mertk in promoting SCI recovery through its ability to mitigate BSCB permeability and may provide potential targets for SCI repair.

Dai, Menghan; Li, Jie; Hao, Xiangwen; Li, Na; Zheng, Mingfang; He, Miao; Gu, Yu

doi: 10.1007/s12264-024-01242-xpmid: 38833201

Abnormal visual experience during the critical period can cause deficits in visual function, such as amblyopia. High magnesium (Mg2+) supplementary can restore ocular dominance (OD) plasticity, which promotes the recovery of amblyopic eye acuity in adults. However, it remains unsolved whether Mg2+ could recover binocular vision in amblyopic adults and what the molecular mechanism is for the recovery. We found that in addition to the recovery of OD plasticity, binocular integration can be restored under the treatment of high Mg2+ in amblyopic mice. Behaviorally, Mg2+-treated amblyopic mice showed better depth perception. Moreover, the effect of high Mg2+ can be suppressed with transient receptor potential melastatin-like 7 (TRPM7) knockdown. Collectively, our results demonstrate that high Mg2+ could restore binocular visual functions from amblyopia. TRPM7 is required for the restoration of plasticity in the visual cortex after high Mg2+ treatment, which can provide possible clinical applications for future research and treatment of amblyopia.

Sun, Dexin; Zhang, Zhilin; Oishi, Naoya; Dai, Qi; Thuy, Dinh Ha Duy; Abe, Nobuhito; Tachibana, Jun; Funahashi, Shintaro; Wu, Jinglong; Murai, Toshiya; Fukuyama, Hidenao

doi: 10.1007/s12264-024-01251-wpmid: 38937384

The activity of occipitotemporal regions involved in linguistic reading processes, such as the ventral occipitotemporal cortex (vOT), is believed to exhibit strong interactions during higher-order language processing, specifically in the connectivity between the occipital gyrus and the temporal gyrus. In this study, we utilized functional magnetic resonance imaging (fMRI) with psychophysiological interaction (PPI) and dynamic causal modeling (DCM) to investigate the functional and effective connectivity in the occipitotemporal network during speed reading. We conducted the experiment with native Japanese speakers who underwent and without speed-reading training and subsequently performed established reading tasks at different speeds (slow, medium, and fast) while undergoing 3-Tesla Siemens fMRI. Our activation analyses revealed significant changes in occipital and temporal regions as reading speed increased, indicating functional connectivity within the occipitotemporal network. DCM results further demonstrated more intricate effective connections and high involvement within the occipitotemporal pathway: (1) reading signals originated from the inferior occipital gyrus (iO), distributed to the vOT and the posterior superior temporal sulcus (pSTS), and then gathered in the anterior superior temporal sulcus (aSTS); (2) reading speed loads had modulation effects on the pathways from the aSTS to vOT and from the iO to vOT. These findings highlight the complex connectivity and dynamic interactions within the occipitotemporal network during speed-reading processes.

Kang, Xiaopeng; Wang, Dawei; Lin, Jiaji; Yao, Hongxiang; Zhao, Kun; Song, Chengyuan; Chen, Pindong; Qu, Yida; Yang, Hongwei; Zhang, Zengqiang; Zhou, Bo; Han, Tong; Liao, Zhengluan; Chen, Yan; Lu, Jie; Yu, Chunshui; Wang, Pan; Zhang, Xinqing; Li, Ming; Zhang, Xi; Jiang, Tianzi;

Liu, Linglin; Luo, Lanzhi; Wei, Ji-an; Xu, Xintong; So, Kwok-Fai; Zhang, Li

doi: 10.1007/s12264-024-01226-xpmid: 38807019

Alcohol abuse induces various neurological disorders including motor learning deficits, possibly by affecting neuronal and astrocytic activity. Physical exercise is one effective approach to remediate synaptic loss and motor deficits as shown by our previous works. In this study, we unrevealed the role of exercise training in the recovery of cortical neuronal and astrocytic functions. Using a chronic alcohol injection mouse model, we found the hyperreactivity of astrocytes along with dendritic spine loss plus lower neuronal activity in the primary motor cortex. Persistent treadmill exercise training, on the other hand, improved neural spine formation and inhibited reactive astrocytes, alleviating motor learning deficits induced by alcohol exposure. These data collectively support the potency of endurance exercise in the rehabilitation of motor functions under alcohol abuse.

Liu, Jingjing; Ye, Jialin; Ji, Chunyuan; Ren, Wenting; He, Youwei; Xu, Fuqiang; Wang, Feng

doi: 10.1007/s12264-024-01237-8pmid: 38900384

Autism spectrum disorders (ASD) are characterized by social and repetitive abnormalities. Although the ASD mouse model with Shank3b mutations is widely used in ASD research, the behavioral phenotype of this model has not been fully elucidated. Here, a 3D-motion capture system and linear discriminant analysis were used to comprehensively record and analyze the behavioral patterns of male and female Shank3b mutant mice. It was found that both sexes replicated the core and accompanied symptoms of ASD, with significant sex differences. Further, Shank3b heterozygous knockout mice exhibited distinct autistic behaviors, that were significantly different from those those observed in the wild type and homozygous knockout groups. Our findings provide evidence for the inclusion of both sexes and experimental approaches to efficiently characterize heterozygous transgenic models, which are more clinically relevant in autistic studies.

Ji, Yanru; McLean, Jenna Lillie; Xu, Ranjie

doi: 10.1007/s12264-024-01189-zpmid: 38466557

Human pluripotent stem cell (hPSC) models provide unprecedented opportunities to study human neurological disorders by recapitulating human-specific disease mechanisms. In particular, hPSC-based human–animal brain chimeras enable the study of human cell pathophysiology in vivo. In chimeric brains, human neural and immune cells can maintain human-specific features, undergo maturation, and functionally integrate into host brains, allowing scientists to study how human cells impact neural circuits and animal behaviors. The emerging human–animal brain chimeras hold promise for modeling human brain cells and their interactions in health and disease, elucidating the disease mechanism from molecular and cellular to circuit and behavioral levels, and testing the efficacy of cell therapy interventions. Here, we discuss recent advances in the generation and applications of using human–animal chimeric brain models for the study of neurological disorders, including disease modeling and cell therapy.

Guo, Jing; He, Changyi; Song, Huimiao; Gao, Huiwu; Yao, Shi; Dong, Shan-Shan; Yang, Tie-Lin

doi: 10.1007/s12264-024-01214-1pmid: 38703276

Schizophrenia is a complex and serious brain disorder. Neuroscientists have become increasingly interested in using magnetic resonance-based brain imaging-derived phenotypes (IDPs) to investigate the etiology of psychiatric disorders. IDPs capture valuable clinical advantages and hold biological significance in identifying brain abnormalities. In this review, we aim to discuss current and prospective approaches to identify potential biomarkers for schizophrenia using clinical multimodal neuroimaging and imaging genetics. We first described IDPs through their phenotypic classification and neuroimaging genomics. Secondly, we discussed the applications of multimodal neuroimaging by clinical evidence in observational studies and randomized controlled trials. Thirdly, considering the genetic evidence of IDPs, we discussed how can utilize neuroimaging data as an intermediate phenotype to make association inferences by polygenic risk scores and Mendelian randomization. Finally, we discussed machine learning as an optimum approach for validating biomarkers. Together, future research efforts focused on neuroimaging biomarkers aim to enhance our understanding of schizophrenia.

Meng, Han; Huan, Yu; Zhang, Kun; Yi, Xuyang; Meng, Xinyu; Kang, Enming; Wu, Shengxi; Deng, Wenbing; Wang, Yazhou

doi: 10.1007/s12264-024-01206-1pmid: 38656419

The existence of neural stem cells (NSCs) in the adult mammalian nervous system, although small in number and restricted to the sub-ventricular zone of the lateral ventricles, the dentate gyrus of the hippocampus, and the olfactory epithelium, is a gift of evolution for the adaptive brain function which requires persistent plastic changes of these regions. It is known that most adult NSCs are latent, showing long cell cycles. In the past decade, the concept of quiescent NSCs (qNSCs) has been widely accepted by researchers in the field, and great progress has been made in the biology of qNSCs. Although the spontaneous neuronal regeneration derived from adult NSCs is not significant, understanding how the behaviors of qNSCs are regulated sheds light on stimulating endogenous NSC-based neuronal regeneration. In this review, we mainly focus on the recent progress of the developmental origin and regulatory mechanisms that maintain qNSCs under normal conditions, and that mobilize qNSCs under pathological conditions, hoping to give some insights for future study.