ABSTRACT
Background: The commissural inhibitory system between the bilateral medial vestibular nucleus (MVN) plays a key role in vestibular compensation. Calcium-binding protein parvalbumin (PV) is expressed in MVN GABAergic neurons. Whether these neurons are involved in vestibular compensation is still unknown. Methods: After unilateral labyrinthectomy (UL), we measured the activity of MVN PV neurons by in vivo calcium imaging, and observed the projection of MVN PV neurons by retrograde neural tracing. After regulating PV neurons' activity by chemogenetic technique, the effects on vestibular compensation were evaluated by behavior analysis. Results: We found PV expression and the activity of PV neurons in contralateral but not ipsilateral MVN increased 6 h following UL. ErbB4 is required to maintain GABA release for PV neurons, conditional knockout ErbB4 from PV neurons promoted vestibular compensation. Further investigation showed that vestibular compensation could be promoted by chemogenetic inhibition of contralateral MVN or activation of ipsilateral MVN PV neurons. Additional neural tracing study revealed that considerable MVN PV neurons were projecting to the opposite side of MVN, and that activating the ipsilateral MVN PV neurons projecting to contralateral MVN can promote vestibular compensation. Conclusion: Contralateral MVN PV neuron activation after UL is detrimental to vestibular compensation, and rebalancing bilateral MVN PV neuron activity can promote vestibular compensation, via commissural inhibition from the ipsilateral MVN PV neurons. Our findings provide a new understanding of vestibular compensation at the neural circuitry level and a novel potential therapeutic target for vestibular disorders.
ABSTRACT
Single therapeutic interventions have not yet been successful in restoring function after spinal cord injury. Accordingly, combinatorial interventions targeting multiple factors may hold greater promise for achieving maximal functional recovery. In this study, we applied a combinatorial approach of chronic chemogenetic neuronal activation and physical exercise including treadmill running and forelimb training tasks to promote functional recovery. In a mouse model of cervical (C5) dorsal hemisection of the spinal cord, which transects almost all descending corticospinal tract axons, combining selective activation of corticospinal motoneurons (CMNs) by intersectional chemogenetics with physical exercise significantly promoted functional recovery evaluated by the grid walking test, grid hanging test, rotarod test, and single pellet-reaching tasks. Electromyography and histological analysis showed increased activation of forelimb muscles via chemogenetic stimuli, and a greater density of vGlut1+ innervation in spinal cord grey matter rostral to the injury, suggesting enhanced neuroplasticity and connectivity. Combined therapy also enhanced activation of mTOR signaling and reduced apoptosis in spinal motoneurons, Counts revealed increased numbers of detectable choline acetyltransferase-positive motoneurons in the ventral horn. Taken together, the findings from this study validate a novel combinatorial approach to enhance motor function after spinal cord injury.
Subject(s)
Spinal Cord Injuries , Animals , Mice , Motor Neurons/physiology , Spinal Cord/pathology , Pyramidal Tracts/pathology , Axons/pathology , Exercise , Recovery of Function/physiologyABSTRACT
A simple low-cost label-free photoelectrochemical (PEC) biosensing platform based on red blood cell shaped BiVO4 modified g-C3N4 was designed for tetracycline detection under room temperature. The prepared g-C3N4/BiVO4 heterojunction not only demonstrated a high surface area, excellent physicochemical stability and favorable PEC activity, but also can be employed as nanostructure support for aptamers to construct a visible-light-driven PEC aptasensor due to rich π-π accumulation sites. More importantly, the proposed PEC aptasensor showed a favorable linear toward tetracycline in the range from 5 × 10-9 to 2 × 10-7 M with a detection limit of 1.6 nM, which well covered the Food Standards Testing requirements. Practical food sample analysis further revealed the accuracy and feasibility of the g-C3N4/BiVO4 heterostructure based PEC platform. It is expected that such a label-free and cost-effective PEC strategy should act as a promising candidate for tetracycline determination in food quality control and supervision.
Subject(s)
Aptamers, Nucleotide , Biosensing Techniques , Anti-Bacterial Agents/analysis , Aptamers, Nucleotide/chemistry , Electrochemical Techniques , Food Analysis , Limit of Detection , Tetracycline/analysis , CyanidesABSTRACT
Liver-expressed antimicrobial peptide 2 (LEAP2) is a newly discovered antagonist of the growth hormone secretagogue receptor (GHSR) and is considered the first endogenous peptide that can antagonize the metabolic actions of ghrelin. The effects of ghrelin administration on feeding behavior, body weight, and energy metabolism involve the activation of orexigenic neurons in the arcuate nucleus (ARC) of the hypothalamus. It is unclear, however, if LEAP2 applied directly to the ARC of the hypothalamus affects these metabolic processes. Here, we show that overexpression of LEAP2 in the ARC through adeno-associated virus (AAV) reduced food intake and body weight in wild-type (WT) mice fed chow and a high-fat diet (HFD) and improved metabolic disorders. LEAP2 overexpression in the ARC overrides both central and peripheral ghrelin action on a chow diet. Interestingly, this AAV-LEAP2 treatment increased proopiomelanocortin (POMC) expression while agouti-related peptide (AGRP)/neuropeptide Y (NPY) and GHSR levels remained unchanged in the hypothalamus. Additionally, intracerebroventricular (i.c.v.) administration of LEAP2 decreased food intake, increased POMC neuronal activity, and repeated LEAP2 administration to mice induced body weight loss. Using chemogenetic manipulations, we found that inhibition of POMC neurons abolished the anorexigenic effect of LEAP2. These results demonstrate that central delivery of LEAP2 leads to appetite-suppressing and body weight reduction, which might require activation of POMC neurons in the ARC.
Subject(s)
Antimicrobial Cationic Peptides , Eating , Ghrelin , Pro-Opiomelanocortin , Animals , Mice , Body Weight , Ghrelin/pharmacology , Neurons/metabolism , Pro-Opiomelanocortin/genetics , Receptors, Ghrelin/genetics , Receptors, Ghrelin/metabolism , Antimicrobial Cationic Peptides/genetics , Antimicrobial Cationic Peptides/metabolism , Feeding BehaviorABSTRACT
First-principles calculations of undoped HfO(2) and cobalt-doped HfO(2) have been carried out to study the magnetic properties of the dielectric material. In contrast to previous reports, it was found that the native defects in HfO(2) could not induce strong ferromagnetism. However, the cobalt substituting hafnium is the most stable defect under oxidation condition, and the ferromagnetic (FM) coupling between the cobalt substitutions is favorable in various configurations. We found that the FM coupling is mediated by the threefold-coordinated oxygen atoms in monoclinic HfO(2) and could be further enhanced in electron-rich condition.