Timing mechanisms in neuronal pathfinding, synaptic reorganization, and neuronal regeneration

Ivakhnitskaia, Evguenia; Hamada, Kana; Chang, Chieh

doi:10.1111/dgd.12259

Cited by 5 publications

(6 citation statements)

References 33 publications

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“…In a rat model of a middle cerebral artery occlusion and subsequent reperfusion injury, let-7 family members were upregulated at the 48-hour reperfusion time point [ 72 , 74 ]. In C. elegancs, several neurons have shown increased levels of let-7 as they age, whereby let-7 upregulation contributed to the decline of aging neurons’ regeneration potential [ 75 ]. Let-7 microRNAs was downregulated in radiation-exposed neural granule cell progenitors, as well as in medulloblastoma [ 76 ].…”

Section: Discussionmentioning

confidence: 99%

Growth of malignant extracranial tumors alters microRNAome in the prefrontal cortex of TumorGraft mice

et al. 2017

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A wide array of central nervous system complications, neurological deficits, and cognitive impairments occur and persist as a result of systemic cancer and cancer treatments. This condition is known as chemo brain and it affects over half of cancer survivors. Recent studies reported that cognitive impairments manifest before chemotherapy and are much broader than chemo brain alone, thereby adding in tumor brain as a component. The molecular mechanisms of chemo brain are under-investigated, and the mechanisms of tumor brain have not been analyzed at all. The frequency and timing, as well as the long-term persistence, of chemo brain and tumor brain suggest they may be epigenetic in nature. MicroRNAs, small, single-stranded non-coding RNAs, constitute an important part of the cellular epigenome and are potent regulators of gene expression. miRNAs are crucial for brain development and function, and are affected by a variety of different stresses, diseases and conditions. However, nothing is known about the effects of extracranial tumor growth or chemotherapy agents on the brain microRNAome.We used the well-established TumorGraft ™ mouse models of triple negative (TNBC) and progesterone receptor positive (PR+BC) breast cancer, and profiled global microRNAome changes in tumor-bearing mice upon chemotherapy, as compared to untreated tumor-bearing mice and intact mice. Our analysis focused on the prefrontal cortex (PFC), based on its roles in memory, learning, and executive functions, and on published data showing the PFC is a target in chemo brain.This is the first study showing that tumor presence alone significantly impacted the small RNAome of PFC tissues. Both tumor growth and chemotherapy treatment affected the small RNAome and altered levels of miRNAs, piRNAs, tRNAs, tRNA fragments and other molecules involved in post-transcriptional regulation of gene expression. Amongst those, miRNA changes were the most pronounced, involving several miRNA families, such as the miR-200 family and miR-183/96/182 cluster; both were deregulated in tumor-bearing and chemotherapy-treated animals. We saw that miRNA deregulation was associated with altered levels of brain-derived neurotrophic factor (BDNF), which plays an important role in cognition and memory and is one of the known miRNA targets. BDNF downregulation has been associated with an array of neurological conditions and could be one of the mechanisms underlying tumor brain and chemo brain. In the future our study could serve as a roadmap for further analysis of cancer and chemotherapy’s neural side effects, and differentially expressed miRNAs should be explored as potential tumor brain and chemo brain biomarkers.

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Section: Discussionmentioning

confidence: 99%

Growth of malignant extracranial tumors alters microRNAome in the prefrontal cortex of TumorGraft mice

et al. 2017

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“…Many extrinsic and intrinsic factors that act to promote or block neuronal regeneration after nerve injury have been identified [11,16,44,[52][53][54][55][56] , but little is known for the molecular connection between neuronal debris removal and neuronal regeneration. It was recently shown in C. elegans that after peripheral nerve injury, proximal axon debris is removed and axon regenerates.…”

Section: Ced-1 Functions In Engulfing Cells To Promote Axon Regenerationmentioning

confidence: 99%

Engulfment Genes Promote Neuronal Regeneration in Caenorhabditis Elegans: Two Divergent But Complementary Views

Chang

Hisamoto

2020

BioEssays

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Axon regeneration is a conserved process across the animal kingdom. Recent studies using the soil worm Caenorhabditis elegans as a model system revealed that machineries regulating engulfment of dying cells also control axon regeneration and axon debris removal. In this review, we examine the relationships between the engulfment machinery and the biological processes triggered by axon injury and subsequent axon regeneration drawn from divergent views. In one study, it was found that engulfing cells directly promote axon regeneration. In this context, CED-1 (Drosophila Draper/mouse MEGF10), an engulfment protein expressed on the surface of engulfing cells, functions as a receptor for axon debris removal and as an adhesion molecule for axon regeneration. In other studies, it was shown that those engulfment genes, previously known to function within the engulfing cells for cell corpse removal, can have a cell-autonomous "non-engulfing cell" role in axon regeneration. Together, these findings suggest that engulfment genes are repurposed for neuronal regeneration by acting in both engulfing cells and regenerating neurons.

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“…This temporal control is abolished when lin‐4 is removed . The lin‐4‐lin‐14 pathway has also been suggested to regulate the timely transition from axon pathfinding to synapse formation in AVM neurons …”

Section: Overview Of Biological Clocksmentioning

confidence: 99%

Timing of neuronal plasticity in development and aging

Ivakhnitskaia

Lin

Hamada

et al. 2017

WIREs Developmental Biology

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Molecular oscillators are well known for their roles in temporal control of some biological processes like cell proliferation, but molecular mechanisms that provide temporal control of differentiation and postdifferentiation events in cells are less understood. In the nervous system, establishment of neuronal connectivity during development and decline in neuronal plasticity during aging are regulated with temporal precision, but the timing mechanisms are largely unknown. Caenorhabditis elegans has been a preferred model for aging research and recently emerges as a new model for the study of developmental and postdevelopmental plasticity in neurons. In this review we discuss the emerging mechanisms in timing of developmental lineage progression, axon growth and pathfinding, synapse formation, and reorganization, and neuronal plasticity in development and aging. We also provide a current view on the conserved core axon regeneration molecules with the intention to point out potential regulatory points of temporal controls. We highlight recent progress in understanding timing mechanisms that regulate decline in regenerative capacity, including progressive changes of intrinsic timers and co-opting the aging pathway molecules. WIREs Dev Biol 2018, 7:e305. doi: 10.1002/wdev.305 This article is categorized under: Invertebrate Organogenesis > Worms Establishment of Spatial and Temporal Patterns > Regulation of Size, Proportion, and Timing Nervous System Development > Worms Gene Expression and Transcriptional Hierarchies > Regulatory RNA.

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Timing mechanisms in neuronal pathfinding, synaptic reorganization, and neuronal regeneration

Cited by 5 publications

References 33 publications

Growth of malignant extracranial tumors alters microRNAome in the prefrontal cortex of TumorGraft mice

Growth of malignant extracranial tumors alters microRNAome in the prefrontal cortex of TumorGraft mice

Engulfment Genes Promote Neuronal Regeneration in Caenorhabditis Elegans: Two Divergent But Complementary Views

Timing of neuronal plasticity in development and aging

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