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      Neuropilin-2 Signaling Modulates Mossy Fiber Sprouting by Regulating Axon Collateral Formation Through CRMP2 in a Rat Model of Epilepsy

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          Abstract

          Programmed neural circuit formation constitutes the foundation for normal brain functions. Axon guidance cues play crucial roles in neural circuit establishment during development. Whether or how they contribute to maintaining the stability of networks in mature brains is seldom studied. Upon injury, neural rewiring could happen in adulthood, of which mossy fiber sprouting (MFS) is a canonical example. Here, we uncovered a novel role of axon guidance molecule family Sema3F/Npn-2 signaling in MFS and epileptogenesis in a rat model of epilepsy. Dentate gyrus-specific Npn-2 knockdown increased seizure activity in epileptic animals along with increased MFS. Hippocampal culture results suggested that Npn-2 signaling modulates MFS via regulating axon outgrowth and collateral formation. In addition, we discovered that Sema3F/Npn-2 signal through CRMP2 by regulating its phosphorylation in the process of MFS. Our work illustrated that Npn-2 signaling in adult epilepsy animals could potentially modulate seizure activity by controlling MFS. MFS constitutes the structural basis for abnormal electric discharge of neurons and recurrent seizures. Therapies targeting Npn-2 signaling could potentially have disease-modifying anti-epileptogenesis effects in epilepsy treatment.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s12035-022-02995-0.

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          Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.

          The two most commonly used methods to analyze data from real-time, quantitative PCR experiments are absolute quantification and relative quantification. Absolute quantification determines the input copy number, usually by relating the PCR signal to a standard curve. Relative quantification relates the PCR signal of the target transcript in a treatment group to that of another sample such as an untreated control. The 2(-Delta Delta C(T)) method is a convenient way to analyze the relative changes in gene expression from real-time quantitative PCR experiments. The purpose of this report is to present the derivation, assumptions, and applications of the 2(-Delta Delta C(T)) method. In addition, we present the derivation and applications of two variations of the 2(-Delta Delta C(T)) method that may be useful in the analysis of real-time, quantitative PCR data. Copyright 2001 Elsevier Science (USA).
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            Modification of seizure activity by electrical stimulation: II. Motor seizure

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              Dentate gyrus circuits for encoding, retrieval and discrimination of episodic memories

              The dentate gyrus (DG) has a key role in hippocampal memory formation. Intriguingly, DG lesions impair many, but not all hippocampus-dependent mnemonic functions, indicating that the rest of the hippocampus (CA1-CA3) can operate autonomously under certain conditions. An extensive body of theoretical work has proposed how the architectural elements and various cell types of the DG may underlie its function in cognition. Recent studies recorded and manipulated the activity of different neuron types in the DG during memory tasks and opened exciting new insights in the mechanisms of DG computational processes, particularly for encoding, retrieval and discrimination of similar memories. Here, we review these DG-dependent mnemonic functions in light of the new findings and explore mechanistic links between cellular and network properties and the computations performed by the DG.
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                Author and article information

                Contributors
                wang.qiang2@zs-hospital.sh.cn
                wang.xin@zs-hospital.sh.cn
                Journal
                Mol Neurobiol
                Mol Neurobiol
                Molecular Neurobiology
                Springer US (New York )
                0893-7648
                1559-1182
                31 August 2022
                31 August 2022
                2022
                : 59
                : 11
                : 6817-6833
                Affiliations
                [1 ]GRID grid.413087.9, ISNI 0000 0004 1755 3939, Department of Neurology, , Zhongshan Hospital, Fudan University, ; Shanghai, China
                [2 ]GRID grid.8547.e, ISNI 0000 0001 0125 2443, Department of The State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institutes of Brain Science, , Fudan University, ; Shanghai, China
                Author information
                http://orcid.org/0000-0002-9160-8673
                Article
                2995
                10.1007/s12035-022-02995-0
                9525442
                36044155
                235a2b61-5158-4a1d-86f2-7bd9e5b13af2
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 22 April 2022
                : 7 August 2022
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                © Springer Science+Business Media, LLC, part of Springer Nature 2022

                Neurosciences
                neuropilin-2,epilepsy,mossy fiber sprouting,crmp2,axon collateral formation,adult
                Neurosciences
                neuropilin-2, epilepsy, mossy fiber sprouting, crmp2, axon collateral formation, adult

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