Neural Stimulation and Molecular Mechanisms of Plasticity and Regeneration: A Review

Abstract

Neural stimulation modulates the depolarization of neurons, thereby triggering activity-associated mechanisms of neuronal plasticity. Activity-associated mechanisms in turn play a major role in post-mitotic structure and function of adult neurons. Our understanding of the interactions between neuronal behavior, patterns of neural activity, and the surrounding environment is evolving at a rapid pace. Brain derived neurotrophic factor is a critical mediator of activity-associated plasticity, while multiple immediate early genes mediate plasticity of neurons following bouts of neural activity. New research has uncovered genetic mechanisms that govern the expression of DNA following changes in neural activity patterns, including RNAPII pause-release and activity-associated double stranded breaks. Discovery of novel mechanisms governing activity-associated plasticity of neurons hints at a layered and complex molecular control of neuronal response to depolarization. Importantly, patterns of depolarization in neurons are shown to be important mediators of genetic expression patterns and molecular responses. More research is needed to fully uncover the molecular response of different types of neurons-to-activity patterns; however, known responses might be leveraged to facilitate recovery after neural damage. Physical rehabilitation through passive or active exercise modulates neurotrophic factor expression in the brain and spinal cord and can initiate cortical plasticity commensurate with functional recovery. Rehabilitation likely relies on activity-associated mechanisms; however, it may be limited in its application. Electrical and magnetic stimulation direct specific activity patterns not accessible through passive or active exercise and work synergistically to improve standing, walking, and forelimb use after injury. Here, we review emerging concepts in the molecular mechanisms of activity-derived plasticity in order to highlight opportunities that could add value to therapeutic protocols for promoting recovery of function after trauma, disease, or age-related functional decline.

Applications of the SR4G Transgenic Zebrafish Line for Biomonitoring of Stress-Disrupting Compounds: A Proof-of-Concept Study

“…Our findings showed a distinct downregulation of npas4, nr4a1, per2 , and rorcb following developmental exposure to FLX and overnight exposure to VIN in both stressed and unstressed larvae. These four genes are involved in neurogenesis and neural activity in rodent models ( 60 , 63 ). This pattern was not observed for BPA and DEX, demonstrating some specificity of the responses, which might be explained by differences in the mechanism of action of these compounds.…”

Cell Proliferation in the Piriform Cortex of Rats with Motor Cortex Ablation Treated with Growth Hormone and Rehabilitation

“…Some of the treatments applied so far have been: anti-inflammatories, caspase inhibitors, progesterone, erythropoietin, antioxidants, neurotrophic factors (NGF, BDNF) [ 16 , 17 ], growth factors, and growth inhibitor blockers [ 18 ]. In addition to chemical treatments, it is essential to apply physical rehabilitation treatments to lost motor skills [ 19 ]. Previous studies in our laboratory, using embryonic tissue transplants for the recovery of severe injuries of the motor cortex, highlighted the functional recovery of the motor deficit caused by the injury when the animals were forced to use the hand affected by the injury (rehabilitative therapy).…”

Neurostimulation for Stroke Rehabilitation

“…TMS combined with exercise significantly increased expression of Brain-Derived Neurotrophic Factor and TrkB after middle cerebral artery occlusion in rats (Cui et al, 2020). Hogan and colleagues have written a useful review concerning the molecular mechanisms resulting from neural stimulation and those involving neural plasticity (Hogan et al, 2020). More work in the basic neurosciences will be essential to develop protocols based on an understanding of the molecular processes resulting from neurostimulation which will consequently optimize clinical efficacy.…”