Repulsive Environment Attenuation during Adult Mouse Optic Nerve Regeneration

Goulart, Camila Oliveira; Mendonça, Henrique Rocha; Oliveira, Jorge de; Savoldi, Laura Maria Borges; Heringer, Luiza dos Santos; Santos-Rodrigues, Alexandre dos; Paes‐de‐Carvalho, Roberto; Martínez, Ana Maria Blanco

doi:10.1155/2018/5851914

Cited by 11 publications

(6 citation statements)

References 43 publications

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“…(Moore et al, 2009 ; Belin et al, 2015 ; Wang et al, 2018 ). More recently, combinatorial approaches via modulating multiple independent pathways have been shown to promote injured axons to regenerate beyond the optic chiasm into the brain and reform functional synapses with their original targets (Lim et al, 2016 ; Goulart et al, 2018 ). For example, visual stimulation/RHEB1 overexpression led to regenerating axons back to almost all the correct targets.…”

Section: Introductionmentioning

confidence: 99%

Loss of Arid1a Promotes Neuronal Survival Following Optic Nerve Injury

Peng

Dai

et al. 2020

Front. Cell. Neurosci.

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Trauma or neurodegenerative diseases trigger the retrograde death of retinal ganglion cells (RGCs), causing an irreversible functional loss. AT-rich interaction domain 1A (ARID1A), a subunit of the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex, has been shown to play crucial roles in cell homeostasis and tissue regeneration. However, its function in adult RGC regeneration remains elusive. Here, we show that optic nerve injury induces dynamic changes of Arid1a expression. Importantly, deleting Arid1a in mice dramatically promotes RGC survival, but insignificantly impacts axon regeneration after optic nerve injury. Next, joint profiling of transcripts and accessible chromatin in mature RGCs reveals that Arid1a regulates several genes involved in apoptosis and JAK/STAT signaling pathway. Thus, our findings suggest modulation of Arid1a as a potential therapeutic strategy to promote RGC neuroprotection after damage.

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Section: Introductionmentioning

confidence: 99%

Loss of Arid1a Promotes Neuronal Survival Following Optic Nerve Injury

Peng

Dai

et al. 2020

Front. Cell. Neurosci.

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“…Recently, a study showed that Sema3D and PlexinA1 levels were significantly reduced when zymosan and cAMP analog were used to promote regeneration of crushed optic nerve in a rodent model [ 45 ]. Their result is in concert with our finding of loss of dendritic spine by Sema3D over-expression.…”

Section: Discussionmentioning

confidence: 99%

Cerebral Semaphorin3D is a novel risk factor for age-associated cognitive impairment

et al. 2023

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Background We 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. Methods miR-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. Results Cognitive 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. Conclusion Our results highlight the importance of Sema3D in age-associated dementia. Sema3D could be a novel drug target for dementia treatment.

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“…Leaving aside experiments analyzing the different guidance cues expression levels, there are a few gain- and loss- of function experiments analyzing the function of the different guidance cues in axon regeneration. Sema3D, and the receptor PlexinA1, are downregulated in KO:PTEN mice, which are able to regenerate the optical nerve after crush [ 203 ], while another study shows how transgenic mice with mutant PlexinA3 and PlexinA4 showed no regenerative improvements after mice SCI [ 204 ]. In goldfish, Netrin-1 was found binding to RGC regenerative axons, suggesting that these neurons expressing Netrin receptors had a possible role in this signaling during regeneration [ 205 ].…”

Section: Guidance Cues In Axotomy and Axon Regenerationmentioning

confidence: 99%

Unraveling Axon Guidance during Axotomy and Regeneration

Domínguez-Romero¹,

Slater²

2021

IJMS

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During neuronal development and regeneration axons extend a cytoskeletal-rich structure known as the growth cone, which detects and integrates signals to reach its final destination. The guidance cues “signals” bind their receptors, activating signaling cascades that result in the regulation of the growth cone cytoskeleton, defining growth cone advance, pausing, turning, or collapse. Even though much is known about guidance cues and their isolated mechanisms during nervous system development, there is still a gap in the understanding of the crosstalk between them, and about what happens after nervous system injuries. After neuronal injuries in mammals, only axons in the peripheral nervous system are able to regenerate, while the ones from the central nervous system fail to do so. Therefore, untangling the guidance cues mechanisms, as well as their behavior and characterization after axotomy and regeneration, are of special interest for understanding and treating neuronal injuries. In this review, we present findings on growth cone guidance and canonical guidance cues mechanisms, followed by a description and comparison of growth cone pathfinding mechanisms after axotomy, in regenerative and non-regenerative animal models.

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Repulsive Environment Attenuation during Adult Mouse Optic Nerve Regeneration

Cited by 11 publications

References 43 publications

Loss of Arid1a Promotes Neuronal Survival Following Optic Nerve Injury

Loss of Arid1a Promotes Neuronal Survival Following Optic Nerve Injury

Cerebral Semaphorin3D is a novel risk factor for age-associated cognitive impairment

Unraveling Axon Guidance during Axotomy and Regeneration

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