Mossy fiber mis-pathfinding and semaphorin reduction in the hippocampus of α-CaMKII hKO mice

Nakahara, Soichiro; Miyake, Shinichi; Tajinda, Katsunori; Ito, Hiroyuki

doi:10.1016/j.neulet.2015.05.012

Cited by 12 publications

(12 citation statements)

References 24 publications

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“…Furthermore, pathway analysis revealed several nervous system related pathways significantly associated with memory performance. Among them, glioma, mTOR signaling pathway, axon guidance, and Ephrin receptor signaling have been related with memory functions in previous literature [39][40][41][42]; it is of note that mTOR signaling in hippocampus is necessary for memory formation [40], while other associated pathways are somewhat linked with mTOR signaling pathway, which further supports the involvement of these pathways in memory functions.…”

Section: Discussionmentioning

confidence: 55%

Multi-level genomic analyses suggest new genetic variants involved in human memory

et al. 2018

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Development of high-throughput genotyping platforms provides an opportunity to identify new genetic elements related to complex cognitive functions. Taking advantage of multi-level genomic analysis, here we studied the genetic basis of human short-term (STM, n = 1623) and long-term (LTM, n = 1522) memory functions. Heritability estimation based on single nucleotide polymorphism showed moderate (61%, standard error 35%) heritability of short-term memory but almost zero heritability of long-term memory. We further performed a two-step genome-wide association study, but failed to find any SNPs that could pass genome-wide significance and survive replication at the same time. However, suggestive significance for rs7011450 was found in the shared component of the two STM tasks. Further inspections on its nearby gene zinc finger and at-hook domain containing and SNPs around this gene showed suggestive association with STM. In LTM, a polymorphism within branched chain amino acid transaminase 2 showed suggestive significance in the discovery cohort and has been replicated in another independent population of 1862. Furthermore, we performed a pathway analysis based on the current genomic data and found pathways including mTOR signaling and axon guidance significantly associated with STM capacity. These findings warrant further replication in other larger populations.

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Section: Discussionmentioning

confidence: 55%

Multi-level genomic analyses suggest new genetic variants involved in human memory

et al. 2018

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“…For the guidance of the mossy fibers, the axonal projections of granules cells, it has been reported that Sema3A, Sema3E, and Sema3F participate in their correct targeting [85,95,96,97]. These fibers travel to CA3 via suprapyramidal and infrapyramidal bundles to innervate apical dendrites of CA3 pyramidal neurons in the stratum lucidum.…”

Section: Semaphorins Their Receptors and Hippocampal Developmentmentioning

confidence: 99%

Functions of Plexins/Neuropilins and Their Ligands during Hippocampal Development and Neurodegeneration

Gil

Rı́o

2019

Cells

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There is emerging evidence that molecules, receptors, and signaling mechanisms involved in vascular development also play crucial roles during the development of the nervous system. Among others, specific semaphorins and their receptors (neuropilins and plexins) have, in recent years, attracted the attention of researchers due to their pleiotropy of functions. Their functions, mainly associated with control of the cellular cytoskeleton, include control of cell migration, cell morphology, and synapse remodeling. Here, we will focus on their roles in the hippocampal formation that plays a crucial role in memory and learning as it is a prime target during neurodegeneration.

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“…α -CaMKII hKO is a well-studied kinase for its role in learning, memory, and its electrophysiological correlate, long term potentiation. This α -CaMKII hKO mouse displayed impaired working memory, social interaction, and locomotion activity that are reminiscent of clinical symptoms presented by schizophrenia [ 62 ] (Figures 1 and 3 ). The abnormal morphology of mossy fiber identified in α -CaMKII hKO mice is not only a morphological phenotype but also linked to alterations in electrophysiological properties of field excitatory postsynaptic potentials at mossy fiber-CA3 synapses [ 63 ].…”

Section: Rodent Models Of Schizophrenia Display Ectopic Mossy Fibementioning

confidence: 99%

“…Sema3A, a secreted factor known to repel axon guidance, is increased in the developmental stage and prevents mossy fiber outgrowth in the SO region [ 83 ], while knockdown of Sema3A signaling maintains the mossy fiber subfield in the SO [ 50 , 51 ]. In α -CaMKII hKO mice, the Sema3A expression is decreased in the hippocampus, suggesting the involvement of reduced Sema3A in the mispathfindings of the mossy fiber [ 62 ].…”

Section: Possible Molecular and Cellular Mechanism Underlying Ectomentioning

confidence: 99%

Hippocampal Pathophysiology: Commonality Shared by Temporal Lobe Epilepsy and Psychiatric Disorders

Nakahara

Adachi

Ito

et al. 2018

Neuroscience Journal

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Accumulating evidence points to the association of epilepsy, particularly, temporal lobe epilepsy (TLE), with psychiatric disorders, such as schizophrenia. Among these illnesses, the hippocampus is considered the regional focal point of the brain, playing an important role in cognition, psychosis, and seizure activity and potentially suggesting common etiologies and pathophysiology of TLE and schizophrenia. In the present review, we overview abnormal network connectivity between the dentate gyrus (DG) and the Cornus Ammonis area 3 (CA3) subregions of the hippocampus relative to the induction of epilepsy and schizophrenia. In light of our recent finding on the misguidance of hippocampal mossy fiber projection in the rodent model of schizophrenia, we discuss whether ectopic mossy fiber projection is a commonality in order to evoke TLE as well as symptoms related to schizophrenia.

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Mossy fiber mis-pathfinding and semaphorin reduction in the hippocampus of α-CaMKII hKO mice

Cited by 12 publications

References 24 publications

Multi-level genomic analyses suggest new genetic variants involved in human memory

Multi-level genomic analyses suggest new genetic variants involved in human memory

Functions of Plexins/Neuropilins and Their Ligands during Hippocampal Development and Neurodegeneration

Hippocampal Pathophysiology: Commonality Shared by Temporal Lobe Epilepsy and Psychiatric Disorders

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