ArticleCell communication and signaling : CCS2023
Cerebral Semaphorin3D is a novel risk factor for age-associated cognitive impairment.
Article in Cell communication and signaling : CCS, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 7 citations in OpenAlex.
- Neuron-Derived Sema3B Facilitates Microglial Hematoma Clearance After Intracerebral Hemorrhage.Antioxidants (Basel, Switzerland) · 2026Article
- Brain transcriptomics highlight abundant gene expression and splicing alterations in non-neuronal cells in aFTLD-U.Acta neuropathologica · 2025Article
- JC124 confers multimodal neuroprotection in epilepsy by suppressing NLRP3 inflammasome activation: evidence from animal and human neuronal models.Cell communication and signaling : CCS · 2025Article
- Inhibition of Semaphorin 3A in Hippocampus Alleviates Postpartum Depression-Like Behaviors in Mice.Molecular neurobiology · 2025Article
- A Rare Case of Polymicrogyria in an Elderly Individual With Unique Polygenic Underlining.Cureus · 2024Article
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Authors and funding
11 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWe previously reported that miR-195 exerts neuroprotection by inhibiting Sema3A and cerebral miR-195 levels decreased with age, both of which urged us to explore the role of miR-195 and miR-195-regulated Sema3 family members in age-associated dementia.
methodsmiR-195a KO mice were used to assess the effect of miR-195 on aging and cognitive functions. Sema3D was predicted as a miR-195 target by TargetScan and then verified by luciferase reporter assay, while effects of Sema3D and miR-195 on neural senescence were assessed by beta-galactosidase and dendritic spine density. Cerebral Sema3D was over-expressed by lentivirus and suppressed by si-RNA, and effects of over-expression of Sema3D and knockdown of miR-195 on cognitive functions were assessed by Morris Water Maze, Y-maze, and open field test. The effect of Sema3D on lifespan was assessed in Drosophila. Sema3D inhibitor was developed using homology modeling and virtual screening. One-way and two-way repeated measures ANOVA were applied to assess longitudinal data on mouse cognitive tests.
resultsCognitive impairment and reduced density of dendritic spine were observed in miR-195a knockout mice. Sema3D was identified to be a direct target of miR-195 and a possible contributor to age-associated neurodegeneration as Sema3D levels showed age-dependent increase in rodent brains. Injection of Sema3D-expressing lentivirus caused significant memory deficits while silencing hippocampal Sema3D improved cognition. Repeated injections of Sema3D-expressing lentivirus to elevate cerebral Sema3D for 10 weeks revealed a time-dependent decline of working memory. More importantly, analysis of the data on the Gene Expression Omnibus database showed that Sema3D levels were significantly higher in dementia patients than normal controls (p < 0.001). Over-expression of homolog Sema3D gene in the nervous system of Drosophila reduced locomotor activity and lifespan by 25%. Mechanistically, Sema3D might reduce stemness and number of neural stem cells and potentially disrupt neuronal autophagy. Rapamycin restored density of dendritic spines in the hippocampus from mice injected with Sema3D lentivirus. Our novel small molecule increased viability of Sema3D-treated neurons and might improve autophagy efficiency, which suggested Sema3D could be a potential drug target. Video Abstract
conclusionOur results highlight the importance of Sema3D in age-associated dementia. Sema3D could be a novel drug target for dementia treatment.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.