Enhanced phrenic motor neuron BDNF expression elicited by daily acute intermittent hypoxia is undermined in rats with chronic cervical spinal cord injury.

Acute intermittent hypoxia (AIH) elicits spinal neuroplasticity and is emerging as a potential therapeutic modality to improve respiratory and non-respiratory motor function in people with chronic incomplete spinal cord injury (SCI). Brain-derived neurotrophic factor (BDNF) is necessary and sufficient for moderate AIH-induced phrenic long-term facilitation, a well-studied form of respiratory motor plasticity. Repetitive daily AIH (dAIH) enhances BDNF expression within the phrenic motor neurons of normal rats, but its effects on BDNF after chronic cervical spinal cord injury (cSCI) are unknown.

Prolonged intermittent hypoxia differentially regulates phrenic motor neuron serotonin receptor expression in rats following chronic cervical spinal cord injury.

Low-dose (< 2 h/day), acute intermittent hypoxia (AIH) elicits multiple forms of serotonin-dependent phrenic motor plasticity and is emerging as a promising therapeutic strategy to restore respiratory and non-respiratory motor function after spinal cord injury (SCI). In contrast, high-dose (> 8 h/day), chronic intermittent hypoxia (CIH) undermines some forms of serotonin-dependent phrenic motor plasticity and elicits pathology. CIH is a hallmark of sleep disordered breathing, which is highly prevalent in individuals with cervical SCI.

Intermittent Hypoxia Differentially Regulates Adenosine Receptors in Phrenic Motor Neurons with Spinal Cord Injury.

Cervical spinal cord injury (cSCI) impairs neural drive to the respiratory muscles, causing life- threatening complications such as respiratory insufficiency and diminished airway protection. Repetitive "low dose" acute intermittent hypoxia (AIH) is a promising strategy to restore motor function in people with chronic SCI. Conversely, "high dose" chronic intermittent hypoxia (CIH; ∼8 h/night), such as experienced during sleep apnea, causes pathology.

Dose-dependent phosphorylation of endogenous Tau by intermittent hypoxia in rat brain.

Intermittent hypoxia, or intermittent low oxygen interspersed with normal oxygen levels, has differential effects that depend on the "dose" of hypoxic episodes (duration, severity, number per day, and number of days). Whereas "low dose" daily acute intermittent hypoxia (dAIH) elicits neuroprotection and neuroplasticity, "high dose" chronic intermittent hypoxia (CIH) similar to that experienced during sleep apnea elicits neuropathology. Sleep apnea is comorbid in >50% of patients with Alzheimer's disease-a progressive, neurodegenerative disease associated with brain amyloid and chronic Tau dysregulation (pathology).

Daily acute intermittent hypoxia enhances serotonergic innervation of hypoglossal motor nuclei in rats with and without cervical spinal injury.

Intermittent hypoxia elicits protocol-dependent effects on hypoglossal (XII) motor plasticity. Whereas low-dose, acute intermittent hypoxia (AIH) elicits serotonin-dependent plasticity in XII motor neurons, high-dose, chronic intermittent hypoxia (CIH) elicits neuroinflammation that undermines AIH-induced plasticity. Preconditioning with repeated AIH and mild CIH enhance AIH-induced XII motor plasticity.

Phrenic motor neuron survival below cervical spinal cord hemisection.

Cervical spinal cord injury (cSCI) severs bulbospinal projections to respiratory motor neurons, paralyzing respiratory muscles below the injury. C2 spinal hemisection (C2Hx) is a model of cSCI often used to study spontaneous and induced plasticity and breathing recovery post-injury. One key assumption is that C2Hx dennervates motor neurons below the injury, but does not affect their survival.

Serotonergic innervation of respiratory motor nuclei after cervical spinal injury: Impact of intermittent hypoxia.

Although cervical spinal cord injury (cSCI) disrupts bulbo-spinal serotonergic projections, partial recovery of spinal serotonergic innervation below the injury site is observed after incomplete cSCI. Since serotonin contributes to functional recovery post-injury, treatments to restore or accelerate serotonergic reinnervation are of considerable interest. Intermittent hypoxia (IH) was reported to increase serotonin innervation near respiratory motor neurons in spinal intact rats, and to improve function after cSCI.

Protocol-Specific Effects of Intermittent Hypoxia Pre-Conditioning on Phrenic Motor Plasticity in Rats with Chronic Cervical Spinal Cord Injury.

"Low-dose" acute intermittent hypoxia (AIH; 3-15 episodes/day) is emerging as a promising therapeutic strategy to improve motor function after incomplete cervical spinal cord injury (cSCI). Conversely, chronic "high-dose" intermittent hypoxia (CIH; > 80-100 episodes/day) elicits multi-system pathology and is a hallmark of sleep apnea, a condition highly prevalent in individuals with cSCI. Whereas daily AIH (dAIH) enhances phrenic motor plasticity in intact rats, it is abolished by CIH.

Cervical spinal contusion alters Na-K-2Cl- and K-Cl- cation-chloride cotransporter expression in phrenic motor neurons.

Spinal chloride-dependent synaptic inhibition is critical in regulating breathing and requires neuronal chloride gradients established by cation-chloride cotransporters Na-K-2Cl (NKCC1) and K-Cl (KCC2). Spinal transection disrupts NKCC1/KCC2 balance, diminishing chloride gradients in neurons below injury, contributing to spasticity and chronic pain. It is not known if similar disruptions in NKCC1/KCC2 balance occur in respiratory motor neurons after incomplete cervical contusion (C2SC).

Mechanisms of Enhanced Phrenic Long-Term Facilitation in Rats.

Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron disease, causing muscle paralysis and death from respiratory failure. Effective means to preserve/restore ventilation are necessary to increase the quality and duration of life in ALS patients. At disease end-stage in a rat ALS model ( ), acute intermittent hypoxia (AIH) restores phrenic nerve activity to normal levels via enhanced phrenic long-term facilitation (pLTF).

Circadian genes, xBmal1 and xNocturnin, modulate the timing and differentiation of somites in Xenopus laevis.

We have been investigating whether xBmal1 and xNocturnin play a role in somitogenesis, a cyclic developmental process with an ultradian period. Previous work from our lab shows that circadian genes (xPeriod1, xPeriod2, xBmal1, and xNocturnin) are expressed in developing somites. Somites eventually form the vertebrae, muscles of the back, and dermis.

Advancements in using TiO2 bionanoconjugates for precision degradation of intracellular biological structures.

Due to their low cost, photocatalytic properties, and unique surface chemistry, titanium dioxide (TiO2) nanoparticles are among the most widely used nanoparticles in industry today. Over the last decade, TiO2 nanoparticles have also been chemically and biologically enhanced to create TiO2 bionanoconjugates that can be used for biological applications such as imaging and manipulating desired biological structures. This review particularly focuses on the manner in which these specific chemical and biological modifications in TiO2 bionanoconjugates alter pre and post photoexcitation events to enable precision degradation of intracellular biological structures.