<i>C. elegans</i>as a genetic model to identify novel cellular and molecular mechanisms underlying nervous system regeneration

Chiu, Hui; Alqadah, Amel; Chuang, Chiou-Fen; Chang, Chieh

doi:10.4161/cam.5.5.17985

Cited by 21 publications

(14 citation statements)

References 73 publications

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“…Animals have been mechanically drug-induced or genetically manipulated to model the aging process (Woodruff-Pak, 2008; Tomobe and Nomura, 2009; Bilkei-Gorzo, 2014; Mitchell et al, 2015). Likewise, invertebrates are also employed (Yeoman and Faragher, 2001; Woodruff-Pak, 2008; Chiu et al, 2011). These models have proven to be useful in the study of physiological processes related to aging and neurodegeneration.…”

Section: Introductionmentioning

confidence: 99%

Evidence of Tau Hyperphosphorylation and Dystrophic Microglia in the Common Marmoset

Rodríguez-Callejas

Fuchs

Pérez-Cruz

2016

Front. Aging Neurosci.

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Common marmosets (Callithrix jacchus) have recently gained popularity in biomedical research as models of aging research. Basically, they confer advantages from other non-human primates due to their shorter lifespan with onset of appearance of aging at 8 years. Old marmosets present some markers linked to neurodegeneration in the brain such as amyloid beta (Aβ)1-42 and Aβ1-40. However, there are no studies exploring other cellular markers associated with neurodegenerative diseases in this non-human primate. Using immunohistochemistry, we analyzed brains of male adolescent, adult, old, and aged marmosets. We observed accumulation of Aβ1-40 and Aβ1-42 in the cortex of aged subjects. Tau hyperphosphorylation was already detected in the brain of adolescent animals and increased with aging in a more fibrillary form. Microglia activation was also observed in the aging process, while a dystrophic phenotype accumulates in aged subjects. Interestingly, dystrophic microglia contained hyperphosphorylated tau, but active microglia did not. These results support previous findings regarding microglia dysfunctionality in aging and neurodegenerative diseases as Alzheimer’s disease. Further studies should explore the functional consequences of these findings to position this non-human primate as animal model of aging and neurodegeneration.

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Section: Introductionmentioning

confidence: 99%

Evidence of Tau Hyperphosphorylation and Dystrophic Microglia in the Common Marmoset

Rodríguez-Callejas

Fuchs

Pérez-Cruz

2016

Front. Aging Neurosci.

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“…Laser axotomy in nematodes provides the means for in vivo single axon regeneration studies, a simplified examination into axonal regrowth presently unachievable in more complex vertebrate neuronal systems. Subsequent to laser axotomy, the motor neurons of C. elegans can regenerate and functionally recover [33]. Since each neuron must be targeted and individually severed, the technique is somewhat limited.…”

Section: Invertebrate Models Of Axonal Degeneration and Regenerationmentioning

confidence: 99%

Studying Axonal Degeneration and Regeneration Using In Vitro and In Vivo Models: the Translational Potential

Donaldson

Höke

2014

Future Neurol.

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Since the initial studies by Cajal, multiple models of peripheral nerve degeneration and regeneration have been developed to address the ever-increasing complexity of the mechanisms involved in regeneration. In vitro models offer the principal benefit of a system that can be readily manipulated to address specific mechanistic questions in a deconstructed system. However, in vitro models can be overly simplified and intricacies of the interactions between neurons and glia can be lost. In vivo animal models seek to remedy some of these shortcomings, but most in vivo animal systems fail to precisely model human nerve regeneration. Rodent models of chronic nerve regeneration have been developed to better recapitulate human nerve regeneration, but are not widely used. An important development in the field has been the establishment of experimental nerve regeneration in humans, involving the reinnervation of the epidermis after cutaneous axotomy or topical capsaicin application. Use of such human models will likely accelerate the development and evaluation of new drugs that enhance peripheral nerve regeneration. KeywordsGiven the complexity of the human peripheral nervous system, a wide spectrum of models has been developed over the years to advance the field of axonal degeneration and regeneration. Predominantly, these systems of neuronal degenerative and regenerative processes have been established in model organisms, particularly in rodents and occasionally in subhuman primates. These animal systems have significantly advanced the understanding of the molecular mechanisms of how axons degenerate and regenerate and have provided an initial subject to test novel drug therapies and surgical techniques to improve regeneration after human nerve injuries.In vitro animal models have served to simplify the field of study, reducing the variable factors that are inherently present in whole organism systems. With a range of methods available, there is the potential to study the interactions of neuronal and glial cell populations or with the advent of microtechnologies, to more precisely examine regeneration at the level of the individual axon. Narrowing the lens through which to view degeneration and regeneration, in vitro models permit a greater degree of manipulation and control of the microenvironment and the potential for rapid-paced drug-screening investigations.While in vitro techniques offer highly controllable systems of study, in vivo animal models provide a closer resemblance to the human condition of nerve injury and repair. Investigating the recovery process following nerve injury in living organisms permits a more authentic glimpse into regeneration as whole body system interactions are maintained. Preserving the integrity of the neuronal environment, in vivo animal nerve injury and repair methods model the complexity of the nervous system recovery, but lack some of the precision associated with in vitro methods.Developed over the last few decades, human models of regeneration emerged as a promising novel system t...

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“…In AVM neurons, let‐7 plays a significant role in the decline of the regeneration potential as neurons age (Chiu et al . ; Chiu & Chang ; Zou et al . ).…”

Section: Temporal Control Of Neuronal Regeneration By Let‐7 Mirnamentioning

confidence: 99%

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

2016

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Precise temporal control of neuro-differentiation and postdifferentiation events is necessary for the creation of appropriate wiring diagram in the brain. To make advances in the treatment of neurodevelopmental and neurodegenerative disorders, and traumatic brain injury, it is important to understand these mechanisms. Caenorhabditis elegans has emerged as a revolutionary tool for the study of neural circuits due to its genetic homology to vertebrates and ease of genetic manipulation. microRNA (miRNA), a ubiquitous class of small non-coding RNA, that inhibits the expression of target genes, has emerged as an important timing control molecule through research conducted on C. elegans. This review will focus on the temporal control of neurodifferentiation and post-differentiation events exerted by the two conserved miRNAs, lin-4 and let-7. We summarize recent findings on the role of lin-4 as a timing regulator controlling transition of sequential events in neuronal pathfinding and synaptic remodeling, and the role of let-7 as a timing regulator that limits the regeneration potential of post-differentiated AVM neurons as they age.

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C. elegansas a genetic model to identify novel cellular and molecular mechanisms underlying nervous system regeneration

Cited by 21 publications

References 73 publications

Evidence of Tau Hyperphosphorylation and Dystrophic Microglia in the Common Marmoset

Evidence of Tau Hyperphosphorylation and Dystrophic Microglia in the Common Marmoset

Studying Axonal Degeneration and Regeneration Using In Vitro and In Vivo Models: the Translational Potential

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

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