查看更多>>摘要：intermediate and deep layers of the optic tectum (OT) contain neurons that are sensitive to small continuously moving targets. The sensitivity of these neurons to continuously moving targets suggests directed energy accumulation in the dendrite field of these neurons. Considering that the activation of a single dendrite can induce somatic spikes in vitro, we suggest the mechanism underlying the sequential probability activation of soma. The simulation model of these neurons constructed in combination with the above assumptions qualitatively reproduces the response characteristics of neurons to multi-sized stimuli and continuous sensitivity stimuli observed in physiological experiments. We used the characteristics of continuous motion-sensitive neurons that prefer long-lasting motion and single dendrite activation to induce somatic spikes as the entry point to construct the neuron encoding model. This model will enhance our understanding of the information-processing mechanism of the OT area of bird neurons in perceiving weak targets, and has important theoretical and practical significance for the construction of new brain-like algorithms. (c) 2022 IBRO. Published by Elsevier Ltd. All rights reserved.
查看更多>>摘要：ischemia/reperfusion (I/R) injury is the continuation and deterioration of ischemic injury, and there are no effective treatment strategies for this condition. It has been reported that microRNAs (miRNAs) are considered as potential targets to protect the brain against I/R injury. Previous studies have shown that miR-489-3p plays a vital role in regulating apoptosis of neurons. miR-489-3p is considered as a potential target to pro-tect the brain against I/R injury-induced neuron apoptosis. This study aimed to explore the molecular mechanism of miR-489-3p in protection against cerebral I/R injury. A rat model with cerebral I/R injury was established using the MCAO method. The cell model was constructed using the oxygen glucose deprivation (OGD) method. The expression of miR-489-3p was detected by qRT-PCR. The expression of HDAC2 was detected by Western blot assay and immunofluorescence assay. Cell apoptosis was evaluated by flow cytometry and TUNEL staining assay. The relationship between miR-489-3p and HDAC2 was determined by bioinformatics analysis and lucifer-ase reporter assay. Rescue experiments were performed to investigate the mechanism of the miR-489-3p/HDAC2 axis. miR-489-39 was significantly downregulated, while HDAC2 was upregulated during cerebral I/R injury both in vitro and in vivo. Upregulation of miR-489-3p obviously attenuated cerebral I/R injury by increasing PC12 cell viability, reducing LDH release, and inhibiting cell apoptosis. HDAC2 was identified as a direct target of miR-489-3p. Silencing of HDAC2 showed a neuroprotective effect against OGD/R injury in vitro. Overexpression of HDAC2 significantly attenuated the protective effects of miR-489-3p mimics on cell injury in vitro. Our results revealed that the upregulation of miR-489-3p attenuated cerebral I/R injury by negatively regulating HDAC2. (c) 2021 IBRO. Published by Elsevier Ltd. All rights reserved.
查看更多>>摘要：in the neuronal connection that succumbs to the impairment of sensory and motor neurons are the hallmarks of spinal cord injury (SCI). Secondary pathogenesis, which initiates after the primary mechanical insult to the spinal cord, depicts a pivotal role in producing inflammation, lesion formation and ultimately causes fibrotic scar formation in the chronic period. This fibrotic scar formed acts as a major hindrance in facilitating axo-nal regeneration and is one of the root causes of motor impairment. Cascade of secondary events in SCI begins with injury-induced blood spinal cord barrier rupture that promotes increased migration of neutrophils, macro-phages, and other inflammatory cells at the injury site to initiate the secondary damages. This phenomenon leads to the release of matrix metalloproteinase, cytokines and chemokines, reactive oxygen species, and other prote-olytic enzymes at the lesion site. These factors assist in the activation of the TGF-b1 signaling pathway, which further leads to excessive proliferation of perivascular fibroblast, followed by deposition of collagen and fibronec-tin matrix, which are the main components of the fibrotic scar. Subsequently, this scar formed inhibits the prop-agation of action potential from one neuron to adjacent neurons. Ethamsylate, an anti-hemorrhagic drug, has the potential to maintain early hemostasis as well as restore capillary resistance. Therefore, we hypothesized that ethamsylate, by virtue of its anti-hemorrhagic activity, reduces hemorrhagic ischemia-induced neuronal apopto-sis, maintains the blood spinal cord barrier integrity, and decreases secondary damage severity, thereby reduce the extent of fibrotic scar formation, and demonstrates a neuroprotective role in SCI. (c) 2021 IBRO. Published by Else-vier Ltd. All rights reserved.
查看更多>>摘要：Recent studies show that overlapping community structure is an important feature of the brain functional network. However, alterations in such overlapping community structure in Alzheimer's disease (AD) patients have not been examined yet. In this study, we investigate the overlapping community structure in AD by using resting-state functional magnetic resonance imaging (rs-fMRI) data. The collective sparse symmetric non-negative matrix factorization (cssNMF) is adopted to detect the overlapping community structure. Experimental results on 28 AD patients and 32 normal controls (NCs) from the ADNI2 dataset show that the two groups have remarkable differences in terms of the optimal number of communities, the hierarchy of communities detected at different scales, network functional segregation, and nodal functional diversity. In particular, the frontal-parietal and basal ganglia networks exhibit significant differences between the two groups. A machine learning framework proposed in this paper for AD detection achieved an accuracy of 76.7% when using the detected community strengths of the frontal-parietal and basal ganglia networks only as input features. These findings provide novel insights into the understanding of pathological changes in the brain functional network organization of AD and show the potential of the community structure-related features for AD detection. (c) 2021 IBRO. Published by Elsevier Ltd. All rights reserved.
查看更多>>摘要：improvement of cognitive deficits in Alzheimer's disease (AD), a common form of dementia, is an unattained therapeutic objective. Gene therapy holds promise for treatment of familial and sporadic forms of AD. p38y, a member of the p38 mitogen-activated protein (MAP) kinase family, inhibits amyloid-p toxicity through regulation of tau phosphorylation. We recently showed that a gene delivery approach increasing p38y resulted in markedly better learning and memory performance in mouse models of AD at advanced stages of amyloid-p- and tau-mediated cognitive impairment. Notably, low-to-moderate expression of p38y had beneficial outcomes on cognition. The impact of high levels of p38y on neuronal function remain unclear. Therefore, we addressed the outcomes of high levels of active p38y on brain function, by direct injection of p38c-encoding adenoassociated virus (AAV) into the forebrain of aged mice of an APP transgenic AD mouse model. While motor function in p38y-expressing APP transgenic mice 2 months post-injection was comparable to control treated APP mice, their activity was markedly reduced in the open field test and included frequent bouts of immobility. Moreover, their learning and memory function was markedly impaired compared to control-treated aged APP mice. These results suggest that high neuronal levels of active p38y emphasize a stress kinase role of p38y, perturbing circuit function in motivation, navigation, and spatial learning. Overall, this work shows excessive neuronal p38y levels can aggravate circuit dysfunction and advises adjustable expression systems will be required for sustainable AD gene therapy based on p38y activity. (c) 2022 IBRO. Published by Elsevier Ltd. All rights reserved.
查看更多>>摘要：the improvement of cancer treatment techniques, increasing attention has been given to chemotherapy-induced cognitive impairment through white matter injury. Clemastine fumarate has been shown to enhance white matter integrity in cuprizone-or hypoxia-induced demyelination mouse models. However, whether clemastine can be beneficial for reversing chemotherapy-induced cognitive impairment remains unexplored. In this study, the mice received oral administration of clemastine after chemotherapy. The open-field test and Morris water maze test were used to evaluate their anxiety, locomotor activity and cognitive function. Luxol Fast Blue staining and transmission electron microscopy were used to detect the morphological damage to the myelin. Demyelination and damage to the mature oligodendrocytes and axons were observed by immunofluorescence and western blotting. Clemastine significantly improved their cognitive function and ameliorated white matter injury in the chemotherapy-treated mice. Clemastine enhanced myelination, promoted oligodendrocyte precursor cell differentiation and increased the neurofilament 200 protein levels in the corpus callosum and hippocampus. We concluded that clemastine rescues cognitive function damage caused by chemotherapy through improving white matter integrity. Remyelination, oligodendrocyte differentiation and the increase of neurofilament protein promoted by clemastine are potential strategies for reversing the cognitive dysfunction caused by chemotherapy. (c) 2022 IBRO. Published by Elsevier Ltd. All rights reserved.
查看更多>>摘要：studies using genomic and functional approaches in the fruit fly Drosophila melanogaster have revealed the effects of viral infection on nervous system homeostasis. An established connection between viral infection and brain function is critical due to its significant contribution to several areas of biomedical research, particularly the molecular pathogenesis of neurotropic viruses, the neurobiology of viral disease, and understanding the genetic basis and pathophysiology of viral tropism. (c) 2021 IBRO. Published by Elsevier Ltd. All rights reserved.
查看更多>>摘要：in rodent models of acute and chronic neurodegenerative disorders have uncovered that glutamate-induced excitotoxic cell death is mediated primarily by extrasynaptic N-methyl-D-aspartate receptors (NMDARs). Rodent neurons can also build up in an activity-dependent manner a protective shield against excitotoxicity. This form of acquired neuroprotection is induced by preconditioning with low doses of NMDA or by activation of synaptic NMDARs triggered by bursts of action potentials. Whether NMDARs in human neurons have similar dichotomous actions in cell death and survival is unknown. To investigate this, we established an induced pluripotent stem cell (iPSC)-derived forebrain organoid model for excitotoxic cell death and explored conditions of NMDAR activation that promote neuronal survival when applied prior to a toxic insult. We found that glutamate induced excitotoxicity in human iPSC-derived neurons is mediated by NMDARs. Treatment of organoids with high concentrations of glutamate or NMDA caused the typical excitotoxicity pathology, comprising structural disintegration, neurite blebbing, shut-off of the transcription factor CRE binding protein (CREB), and cell death. In contrast, bath-applied low doses of NMDA elicited synaptic activity, a robust and sustained increase in CREB phosphorylation as well as function, and upregulation of immediate-early genes, including neuroprotective genes. Moreover, we found that conditions of enhanced synaptic activity increased survival of human iPSC-derived neurons if applied as pre-treatment before toxic NMDA application. These results revealed that both toxic and protective actions of NMDARs are preserved in human neurons. The experimental platform described in this study may prove useful for the validation of neuroprotective gene products and drugs in human neurons. (C) 2021 IBRO. Published by Elsevier Ltd. All rights reserved.
查看更多>>摘要：A new method for analyzing brain complex dynamics and states is presented. This method constructs functional brain graphs and is comprised of two pylons: (a) Operational architectonics (OA) concept of brain and mind functioning. (b) Network neuroscience. In particular, the algorithm utilizes OA framework for a nonparametric segmentation of EEG signals, which leads to the identification of change points, namely abrupt jumps in EEG amplitude, called Rapid Transition Processes (RTPs). Subsequently, the time coordinates of RTPs are used for the generation of undirected weighted complex networks fulfilling a scale-free topology criterion, from which various network metrics of brain connectivity are estimated. These metrics form feature vectors, which can be used in machine learning algorithms for classification and/or prediction. The method is tested in classification problems on an EEG-based BCI data set, acquired from individuals during imagery pronunciation tasks of various words/vowels. The classification results, based on a Naive Bayes classifier, show that the overall accuracies were found to be above chance level in all tested cases. This method was also compared with other state-of-the-art computational approaches commonly used for functional network generation, exhibiting competitive performance. The method can be useful to neuroscientists wishing to enhance their repository of brain research algorithms. (c) 2021 IBRO. Published by Elsevier Ltd. All rights reserved.
Adeyelu, TolulopeShrestha, AmitaAdeniyi, Philip A.Lee, Charles C....
20页
查看更多>>摘要：A spontaneous mutation of the disrupted in schizophrenia 1 (Disc1) gene is carried by the 129S inbred mouse strain. Truncated DISC1 protein in 129S mouse synapses impairs the scaffolding of excitatory postsynaptic receptors and leads to progressive spine dysgenesis. In contrast, C57BL/6 inbred mice carry the wild-type Disc1 gene and exhibit more typical cognitive performance in spatial exploration and executive behavioral tests. Because of the innate Disc1 mutation, adult 129S inbred mice exhibit the behavioral phenotypes of outbred B6 Disc1 knockdown (Disc1(-/-)) or Disc1-L-100P mutant strains. Recent studies in Disc1(-/-) and L-100P mice have shown that impaired excitation-driven interneuron activity and low hippocampal theta power underlie the behavioral phenotypes that resemble human depression and schizophrenia. The current study compared the firing rate and connectivity profile of putative neurons in the CA1 of freely behaving inbred 129S and B6 mice, which have mutant and wild-type Disc1 genes, respectively. In cognitive behavioral tests, 129S mice had lower exploration scores than B6 mice. Furthermore, the mean firing rate for 129S putative pyramidal (pyr) cells and interneurons (int) was significantly lower than that for B6 CA1 neurons sampled during similar tasks. Analysis of pyr/int connectivity revealed a significant delay in synaptic transmission for 129S putative pairs. Sampled 129S pyr/int pairs also had lower detectability index scores than B6 putative pairs. Therefore, the spontaneous Disc1 mutation in the 129S strain attenuates the firing of putative pyr CA1 neurons and impairs spike timing fidelity during cognitive tasks. (C)& nbsp;2021 IBRO. Published by Elsevier Ltd. All rights reserved.
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Elsevier