Motor Neurons Exhibit Sustained Loss of Atrophy Reversal in Immunodeficent Mice

Huang, Zhi; Petitto, John M.

doi:10.4172/2329-6895.1000117

Cited by 2 publications

(7 citation statements)

References 28 publications

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“…Reinjuring the facial nerve stimulates a reversal in the atrophic status of the injured neurons, causing an increase in both their size and number [7]. As described below, data from our research suggests that under normal physiological conditions, the reversal of atrophy and the ability of reinjured facial motor neurons to regain their normal phenotype is dependent on a normal functioning cellular immune system [8,9]. To our knowledge, this is the only model of neuronal atrophy reversal that has been studied in the context of immunity or linked to immune function.…”

Section: Atrophied Neurons Have the Potential To Regenerate Their Phementioning

confidence: 99%

“…This study was designed to test our hypothesis that the normal regeneration of atrophied motor neurons is dependent on normal adaptive immunity, and to determine if there were differences in kinetics of the reversal response between the groups. We compared motor neuron survival and size between WT and RAG2-KO mice in the facial nerve reinjury paradigm at 3 and 28 days post-reinjury [9]. Our results showed that in WT mice, facial motor neurons that were resected for 10 weeks and subsequently reinjured were able to regain fully an apparent 40% loss of countable neurons at 3 days post-reinjury, and nearly half of the magnitude of that that robust increase in neurons was sustained at 28 days post-reinjury.…”

Section: Chronic Axotomy Of Facial Motor Neurons T Cells and Atrophymentioning

confidence: 99%

“…No differences were seen between the WT and RAG2-KO mice in overall microglial cell activity using CD11b expression following reinjury. Together, our research indicates that a large percentage of resected motor neurons did not survive the initial resection in RAG2-KO mice, whereas in the immunologically intact WT mice they atrophied and could be restimulated by reinjury to regenerate their phenotype [8,9]. …”

Section: Chronic Axotomy Of Facial Motor Neurons T Cells and Atrophymentioning

confidence: 99%

“…The research described above showed that many resected motor neurons did not survive the initial facial nerve resection in immunodeficient RAG2-KO mice, whereas in WT mice motor neurons atrophied and could be restimulated by reinjury to robustly regenerate their phenotype. In WT mice of the C57BL/6 background, the duration of the atrophy reversal response peaks between days 3 to 7 post-reinjury, and decreases between day 14 to 28 following the reinjury stimulus [7-9]. Following the reinjury stimulus, resected WT neurons disconnected from their target tissue were able to maintain nearly half the robust gain in the numbers that they exhibited at day 3 post-reinjury.…”

Section: Is This Form Of Neuroplasticity Associated With T Cell Functmentioning

confidence: 99%

“…Following the reinjury stimulus, resected WT neurons disconnected from their target tissue were able to maintain nearly half the robust gain in the numbers that they exhibited at day 3 post-reinjury. Although almost all of the available researches using the facial nerve reinjury model have been conducted in C57BL/6 WT mice to date [7-9], one studying showed that Balb/c mice (which are known to have distinctly different Th1/Th2 bias than C57BL/6 mice) have less robust atrophy reversal [7]. …”

Section: Is This Form Of Neuroplasticity Associated With T Cell Functmentioning

confidence: 99%

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Reversal of Neuronal Atrophy: Role of Cellular Immunity in Neuroplasticity and Aging

Petitto¹

2014

J Neurol Disord

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Emerging evidence indicates that neuroimmunological changes in the brain can modify intrinsic brain processes that are involved in regulating neuroplasticity. Increasing evidence suggests that in some forms of motor neuron injury, many neurons do not die, but reside in an atrophic state for an extended period of time. In mice, facial motor neurons in the brain undergo a protracted period of degeneration or atrophy following resection of their peripheral axons. Reinjuring the proximal nerve stump of the chronically resected facial nerve stimulates a robust reversal of motor neuron atrophy which results in marked increases in both the number and size of injured motor neurons in the facial motor nucleus. In this brief review, we describe research from our lab which indicates that the reversal of atrophy in this injury model is dependent on normal cellular immunity. The role of T cells in this unique form of neuroplasticity following injury and in brain aging, are discussed. The potential role of yet undiscover intrinsic actions of recombination activating genes in the brain are considered. Further research using the facial nerve reinjury model could identify molecular signals involved in neuroplasticity, and lead to new ways to stimulate neuroregenerative processes in neurotrauma and other forms of brain insult and disease.

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Section: Atrophied Neurons Have the Potential To Regenerate Their Phementioning

confidence: 99%

Section: Chronic Axotomy Of Facial Motor Neurons T Cells and Atrophymentioning

confidence: 99%

Section: Chronic Axotomy Of Facial Motor Neurons T Cells and Atrophymentioning

confidence: 99%

Section: Is This Form Of Neuroplasticity Associated With T Cell Functmentioning

confidence: 99%

Section: Is This Form Of Neuroplasticity Associated With T Cell Functmentioning

confidence: 99%

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Reversal of Neuronal Atrophy: Role of Cellular Immunity in Neuroplasticity and Aging

Petitto¹

2014

J Neurol Disord

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Deficiency of adaptive immunity does not interfere with Wallerian degeneration

Cashman

Höke²

2017

PLoS ONE

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Following injury, distal axons undergo the process of Wallerian degeneration, and then cell debris is cleared to create a permissive environment for axon regeneration. The innate and adaptive immune systems are believed to be critical for facilitating the clearance of myelin and axonal debris during this process. However, immunodeficient animal models are regularly used in transplantation studies investigating cell therapies to modulate the degenerative/regenerative response. Given the importance of the immune system in preparing a permissive environment for regeneration by clearing debris, animals lacking, in part or in full, a functional immune system may have an impaired ability to regenerate due to poor myelin clearance, and may, thus, be poor hosts to study modulators of regeneration and degeneration. To study this hypothesis, three different mouse models with impaired adaptive immunity were compared to wild type animals in their ability to degenerate axons and clear myelin debris one week following sciatic nerve transection. Immunofluorescent staining for axons and quantitation of axon density with nerve histomorphometry of the distal stump showed no consistent discrepancy between immunodeficient and wild type animals, suggesting axons tended to degenerate equally between the two groups. Debris clearance was assessed by macrophage density and relative myelin basic protein expression within the denervated nerve stump, and no consistent impairment of debris clearance was found. These data suggested deficiency of the adaptive immune system does not have a substantial effect on axon degeneration one week following axonal injury.

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Motor Neurons Exhibit Sustained Loss of Atrophy Reversal in Immunodeficent Mice

Cited by 2 publications

References 28 publications

Reversal of Neuronal Atrophy: Role of Cellular Immunity in Neuroplasticity and Aging

Reversal of Neuronal Atrophy: Role of Cellular Immunity in Neuroplasticity and Aging

Deficiency of adaptive immunity does not interfere with Wallerian degeneration

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