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

Abstract

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.

AAV-based gene therapy approaches for genetic forms of tauopathies and related neurogenetic disorders

“…On the other hand, in ageassociated tauopathies, brain damage that has already happened at the disease onset is unlikely to be reversed with AAV-based gene therapy. Yet, given the probable ability of atrophic neurons to regenerate their normal function (Huang et al, 2014), the timing of initiation of the treatment would be a crucial factor in its success, with patients with known familial tauopathies treated in the presymptomatic phase having the highest chance of benefiting from treatment (Martier and Konstantinova, 2020). This complicates clinical studies due to necessary long-term follow up.…”

Gene Therapy for Neurodegenerative Diseases: Slowing Down the Ticking Clock

“…Most of the adult onset neurodegenerative diseases have a pre-symptomatic stage and it may take several years to gradually progress into a severe state with progressive neuronal death. While neuronal death cannot be reversed, emerging evidence suggests that neurons in atrophic state can regenerate their normal functions (John and Petitto, 2014). Thus, early treatment before neuron death occurs is likely to provide better protection and could decelerate neuronal death.…”