Enhanced neuronal activity in the healthy brain can induce myelination and behavioral changes. As neuronal activity can be achieved using non-invasive measures, it may be of interest to utilize the innate ability of neuronal activity to instruct myelination as a novel strategy for myelin repair in demyelinating disorders such as multiple sclerosis (MS). Preclinical studies indicate that stimulation of neuronal activity in demyelinated lesions indeed has the potential to improve remyelination and that the stimulation paradigm is an important determinant of success. However, future studies will need to reveal the most efficient stimulation protocols as well as the biological mechanisms implicated. Nonetheless, clinical studies have already explored non-invasive brain stimulation as an attractive therapeutic approach that ameliorates MS symptomatology. However, whether symptom improvement is due to improved myelin repair remains unclear. In this mini-review, we discuss the neurobiological basis and potential of enhancing neuronal activity as a novel therapeutic approach in MS.
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http://dx.doi.org/10.3389/fncel.2021.645240 | DOI Listing |
Brain
January 2025
Institute of Neurological Sciences and Psychiatry, Hacettepe University, 06100, Ankara, Turkey.
Cortical spreading depolarization (CSD), the neurophysiological event believed to underlie aura, may trigger migraine headaches through inflammatory signaling that originates in neurons and spreads to the meninges via astrocytes. Increasing evidence from studies on rodents and migraine patients supports this hypothesis. The transition from pro-inflammatory to anti-inflammatory mechanisms is crucial for resolving inflammation.
View Article and Find Full Text PDFPLoS Genet
January 2025
Department of Molecular Biosciences, Program in Molecular, Cellular, and Developmental Biology, KU Center for Genomics, University of Kansas, Lawrence, Kansas, United States of America.
Recent studies in vertebrates and Caenorhabditis elegans have reshaped models of how the axon guidance cue UNC-6/Netrin functions in dorsal-ventral axon guidance, which was traditionally thought to form a ventral-to-dorsal concentration gradient that was actively sensed by growing axons. In the vertebrate spinal cord, floorplate Netrin1 was shown to be largely dispensable for ventral commissural growth. Rather, short range interactions with Netrin1 on the ventricular zone radial glial stem cells was shown to guide ventral commissural axon growth.
View Article and Find Full Text PDFSci Adv
January 2025
Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
The pathophysiology of neurodevelopmental disorders involves vulnerable neural populations, including striatal circuitry, and convergent molecular nodes, including chromatin regulation and synapse function. Despite this, how epigenetic regulation regulates striatal development is understudied. Recurrent de novo mutations in are associated with intellectual disability and autism.
View Article and Find Full Text PDFSci Adv
January 2025
Department of Neuroscience, Helen Wills Neuroscience Institute, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
Homeostatic sleep regulation is essential for optimizing the amount and timing of sleep for its revitalizing function, but the mechanism underlying sleep homeostasis remains poorly understood. Here, we show that optogenetic activation of locus coeruleus (LC) noradrenergic neurons immediately increased sleep propensity following a transient wakefulness, contrasting with many other arousal-promoting neurons whose activation induces sustained wakefulness. Fiber photometry showed that repeated optogenetic or sensory stimulation caused a rapid reduction of calcium activity in LC neurons and steep declines in noradrenaline/norepinephrine (NE) release in both the LC and medial prefrontal cortex (mPFC).
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Neurovascular Unit Research Group, Korea Brain Research Institute, Daegu 41062, Republic of Korea.
In ephaptic coupling, physically adjacent neurons influence one another's activity via the electric fields they generate. To date, the molecular mechanisms that mediate and modulate ephaptic coupling's effects remain poorly understood. Here, we show that the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel lateralizes the potentially mutual ephaptic inhibition between gustatory receptor neurons (GRNs).
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