Air-stepping in the neonatal mouse: a powerful tool for analyzing early stages of rhythmic limb movement development.

There is a lack of experimental methods in genetically tractable mouse models to analyze the developmental period at which newborns mature weight-bearing locomotion. To overcome this deficit, we introduce methods to study l-3,4-dihydroxyphenylalanine (l-DOPA)-induced air-stepping in mice at postnatal day (P)7 and P10. Air-stepping is a stereotypic rhythmic behavior that resembles mouse walking overground locomotion but without constraints imposed by weight bearing, postural adjustments, or sensory feedback.

Bioluminescent Optogenetics: A Novel Experimental Therapy to Promote Axon Regeneration after Peripheral Nerve Injury.

Functional recovery after peripheral nerve injury (PNI) is poor, mainly due to the slow and incomplete regeneration of injured axons. Experimental therapies that increase the excitability of the injured axons have proven remarkably successful in promoting regeneration, but their clinical applicability has been limited. Bioluminescent optogenetics (BL-OG) uses luminopsins, fusion proteins of light-generating luciferase and light-sensing ion channels that could be used to increase neuronal excitability if exposed to a suitable substrate.

Asparagine Endopeptidase (δ Secretase), an Enzyme Implicated in Alzheimer's Disease Pathology, Is an Inhibitor of Axon Regeneration in Peripheral Nerves.

Asparagine endopeptidase (AEP) is a lysosomal protease implicated in the pathology of Alzheimer's disease (AD). It is known to cleave the axonal microtubule associated protein, Tau, and amyloid precursor protein (APP), both of which might impede axon regeneration following peripheral nerve injury (PNI). Active AEP, AEP-cleaved fragments of Tau (Tau N368), and APP (APP N585) were found in injured peripheral nerves.

Physiological and functional responses of water-cooled versus traditional radiofrequency ablation of peripheral nerves in rats.

Background And Objectives: Several clinical studies have focused on assessing the effectiveness of different radiofrequency ablation (RFA) modalities in pain management. While a direct head-to-head clinical study is needed, results from independent studies suggest that water-cooled RFA (CRFA) may result in longer lasting pain relief than traditional RFA (TRFA). The primary purpose of this study was, therefore, to investigate in a preclinical model, head-to-head differences between the two RFA technologies.

Mutations in the Scn8a DIIS4 voltage sensor reveal new distinctions among hypomorphic and null Na 1.6 sodium channels.

Mutations in the voltage-gated sodium channel gene SCN8A cause a broad range of human diseases, including epilepsy, intellectual disability, and ataxia. Here we describe three mouse lines on the C57BL/6J background with novel, overlapping mutations in the Scn8a DIIS4 voltage sensor: an in-frame 9 bp deletion (Δ9), an in-frame 3 bp insertion (∇3) and a 35 bp deletion that results in a frameshift and the generation of a null allele (Δ35). Scn8a and Scn8a heterozygous mutants display subtle motor deficits, reduced acoustic startle response, and are resistant to induced seizures, suggesting that these mutations reduce activity of the Scn8a channel protein, Na 1.

Chemogenetic Enhancement of Axon Regeneration Following Peripheral Nerve Injury in the SLICK-A Mouse.

The effects of chemogenetics on axon regeneration following peripheral nerve transection and repair were studied in mice expressing a Cre-dependent excitatory designer receptor exclusively activated by designer drugs (DREADD) and Cre-recombinase/yellow fluorescent protein (YFP) in a subset of motor and sensory neurons and cortical motoneurons (SLICK-A). Sciatic nerves were cut and repaired and mice were treated either once, at the time of injury, or five days per week for two weeks with clozapine N-oxide (CNO) (1 mg/kg, i.p.

Differential Expression of and mRNA Isoforms in the Injured and Regenerating Nervous Systems.

In both the central nervous system (CNS) and the peripheral nervous system (PNS), axonal injury induces changes in neuronal gene expression. In the PNS, a relatively well-characterized alteration in transcriptional activation is known to promote axonal regeneration. This transcriptional cascade includes the neurotrophin and the transcription factor .