Environmental insult, disease or trauma can affect the physical integrity of neuronal circuits, and the inability of many neurons to regenerate injured axons invariably leads to irreversible neural dysfunction. The conserved second messenger cyclic adenosine monophosphate (cAMP) can promote axonal re-growth. Widely used pharmacological or genetic approaches to increase intracellular levels of cAMP are often inadequate for precise neural-circuit reconstruction because their activity cannot be easily timed to specific target cells. These shortcomings have prevented the controlled repair of pre-defined neurons at selected time points in whole specimens. Thus, technologies to guide neuronal repair in time and space would enable studies of neural-circuit recovery with unprecedented resolution. Towards this aim, we have implemented a proof-of-principle optogenetic method to promote the selective regeneration of refractory axons in a living vertebrate.
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http://dx.doi.org/10.1016/j.cub.2015.09.038 | DOI Listing |
Toxicon
January 2025
National Council of Research (CNR), Institute of Biochemistry and Cell Biology, 00015 Monterotondo (RM), Italy.
Botulinum neurotoxin type A (BoNT/A) has expanded its therapeutic uses beyond neuromuscular disorders to include treatments for various pain syndromes and neurological conditions. Originally recognized for blocking acetylcholine release at neuromuscular junctions, BoNT/A's effects extend to both peripheral and central nervous systems. Its ability to undergo retrograde transport allows BoNT/A to modulate synaptic transmission and reduce pain centrally, influencing neurotransmitter systems beyond muscle control.
View Article and Find Full Text PDFNeurobiol Dis
January 2025
Department of Neurosurgery, The First Affiliated Hospital of Jinan University, Guangzhou 510632, China. Electronic address:
Central nervous system (CNS) repair after injury is a challenging process limited by inflammation and neuronal apoptosis. This study identifies Wilms' tumor 1-associating protein (WTAP) as a pivotal regulator of neuronal protection and repair through m6A methylation of STAT3 mRNA. By employing spinal cord injury (SCI) as a representative model of CNS injury, transcriptomic analyses reveal WTAP as a key mediator of pathways related to neuronal autophagy and inflammation regulation.
View Article and Find Full Text PDFASN Neuro
January 2025
Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI, USA.
In light of the increasing importance for measuring myelin ratios - the ratio of axon-to-fiber (axon + myelin) diameters in myelin internodes - to understand normal physiology, disease states, repair mechanisms and myelin plasticity, there is urgent need to minimize processing and statistical artifacts in current methodologies. Many contemporary studies fall prey to a variety of artifacts, reducing study outcome robustness and slowing development of novel therapeutics. Underlying causes stem from a lack of understanding of the myelin ratio, which has persisted more than a century.
View Article and Find Full Text PDFMuscle Nerve
January 2025
International Collaboration on Repair Discoveries (ICORD), Vancouver, British Columbia, Canada.
Introduction/aims: Upper limb paralysis is arguably the most limiting consequence of cervical spinal cord injury (cSCI). There is limited knowledge regarding the early structural changes of muscles implicated in grasp/pinch function and upper extremity nerve transfer surgeries. We evaluated: (1) muscle size and echo intensity (EI) in subacute cSCI (2-6 months) and (2) the influence of lower motor neuron (LMN) damage on these ultrasound parameters.
View Article and Find Full Text PDFACS Nano
January 2025
School of Pharmaceutical Sciences, Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, Sun Yat-Sen University, University Town, Guangzhou 510006, China.
Mitochondrial transplantation is a significant therapeutic approach for addressing mitochondrial dysfunction in patients with spinal cord injury (SCI), yet it is limited by rapid mitochondrial deactivation and low transfer efficiency. Here, high-quality mitochondria microfactories (HQ-Mitofactories) were constructed by anchoring Prussian blue nanoenzymes onto mesenchymal stem cells for effective mitochondrial transplantation to treat paralysis from SCI. Notably, the results demonstrated that HQ-Mitofactories could continuously produce vitality-boosting mitochondria with highly interconnected and elongated network structures under oxidative stress by scavenging excessive ROS.
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