Christopher Wilson | Loma Linda University (original) (raw)

Papers by Christopher Wilson

The FASEB Journal, 2019

Gestational long term hypoxia (LTH) is a common prenatal stress caused by maternal anemia, high a... more Gestational long term hypoxia (LTH) is a common prenatal stress caused by maternal anemia, high altitude living, smoking, and other disorders. Such gestational LTH can lead to a variety of cerebrovascular disorders in the neonate that compromise brain blood flow. Local and whole‐cell Ca2+ signals are important to the regulation of cerebrovascular tone. Rapid and localized Ca2+ transients, often referred to as sparks, activate large‐conductance K+ channels (BK), which dilate vessels. Whole‐cell Ca2+ oscillations, in comparison, are important to arterial contraction. Previous work shows that LTH and post‐natal maturity influence BK channel function in basilar arteries, arterial wall Ca2+ signals, cerebrovascular tone, as well as brain blood flow. We hypothesize that LTH‐dependent changes in spontaneous and depolarization mediated Ca2+ sparks and whole‐cell oscillations are important to BK channel activity, arterial wall Ca2+ signals, and vascular reactivity changes our group has previ...

Frontiers in Molecular Neuroscience, 2020

Journal of Perinatology, 2019

Journal of Neurophysiology, 2004

We have developed a single-compartment, electrophysiological, hypoglossal motoneuron (HM) model b... more We have developed a single-compartment, electrophysiological, hypoglossal motoneuron (HM) model based primarily on experimental data from neonatal rat HMs. The model is able to reproduce the fine features of the HM action potential: the fast afterhyperpolarization, the afterdepolarization, and the medium-duration afterhyperpolarization (mAHP). The model also reproduces the repetitive firing properties seen in neonatal HMs and replicates the neuron's response to pharmacological experiments. The model was used to study the role of specific ionic currents in HM firing and how variations in the densities of these currents may account for age-dependent changes in excitability seen in HMs. By varying the density of a fast inactivating calcium current, the model alternates between accelerating and adapting firing patterns. Modeling the age-dependent increase in H current density accounts for the decrease in mAHP duration observed experimentally, but does not fully account for the decre...

Scientific Reports, 2021

We have identified thiolesters that reverse the negative effects of opioids on breathing without ... more We have identified thiolesters that reverse the negative effects of opioids on breathing without compromising antinociception. Here we report the effects of d-cystine diethyl ester (d-cystine diEE) or d-cystine dimethyl ester (d-cystine diME) on morphine-induced changes in ventilation, arterial-blood gas chemistry, A-a gradient (index of gas-exchange in the lungs) and antinociception in freely moving rats. Injection of morphine (10 mg/kg, IV) elicited negative effects on breathing (e.g., depression of tidal volume, minute ventilation, peak inspiratory flow, and inspiratory drive). Subsequent injection of d-cystine diEE (500 μmol/kg, IV) elicited an immediate and sustained reversal of these effects of morphine. Injection of morphine (10 mg/kg, IV) also elicited pronounced decreases in arterial blood pH, pO2 and sO2 accompanied by pronounced increases in pCO2 (all indicative of a decrease in ventilatory drive) and A-a gradient (mismatch in ventilation-perfusion in the lungs). These ef...

World Journal of Pediatric Surgery, 2022

BackgroundNecrotizing enterocolitis (NEC) is the leading gastrointestinal cause of death in prema... more BackgroundNecrotizing enterocolitis (NEC) is the leading gastrointestinal cause of death in premature infants and causes long-term disabilities. Previously, enteral heparin-binding epidermal growth factor-like growth factor (HB-EGF) administered after birth demonstrated decreased incidence and severity of NEC in a neonatal animal model of NEC. We investigated the potential prophylactic strategy of preventing NEC using prenatally administered HB-EGF.MethodsAn HB-EGF (800 µg/kg/dose) dose was injected into pregnant rats via tail vein or intraperitoneal route 2 hours prior to delivery. After cesarean section (C-section) at 21 days’ gestation, the rat pups were subjected to the NEC protocol by inducing stressors: hypoxia, hypothermia, hypertonic feeds, and orogastric gavage of lipopolysaccharide (2 mg/kg). Postnatally, pups were monitored for 96 hours and assessed for the development of clinical and postmortem histological NEC.ResultsThe experimental NEC incidence in untreated, stressed...

Journal of Neuroinflammation, 2019

Background Niemann-Pick disease type C (NPC) is a progressive neurodegenerative condition that re... more Background Niemann-Pick disease type C (NPC) is a progressive neurodegenerative condition that results in early fatality. NPC is inherited in an autosomal recessive pattern from mutations in NPC1 or NPC2 genes. The etiology of NPC is poorly defined. In that regard, neuroinflammation occurs early in the disease and we have recently unveiled an atypical pattern of interferon signaling in pre-symptomatic Npc1−/− mice, with microglial activation, anti-viral response, activation of antigen-presenting cells, and activation and chemotaxis of T lymphocytes as the key affected pathologic pathways. Furthermore, IP-10/CXCL10, a potent IFN-γ-responsive cytokine, was identified as the potential mediator of these early inflammatory abnormalities. Here, we asked whether this aberrant signaling may be exacerbated by the loss of amyloid precursor protein (APP) function, a loss known to shorten lifespan and accelerate neurodegeneration in Npc1−/− mice. Methods We carried out genome-wide comparative t...

Journal of Visualized Experiments, 2019

Scientific reports, Jan 24, 2017

The function of the amyloid precursor protein (APP) in brain health remains unclear. This study e... more The function of the amyloid precursor protein (APP) in brain health remains unclear. This study elucidated a novel cytoprotective signaling pathway initiated by the APP transcriptionally active intracellular domain (AICD) in response to 27-hydroxycholesterol (27OHC), an oxidized cholesterol metabolite associated with neurodegeneration. The cellular response to 27OHC was hormetic, such that low, but not high, doses promoted AICD transactivation of microtubule associated serine/threonine kinase family member 4 (MAST4). MAST4 in turn phosphorylated and inhibited FOXO1-dependent transcriptional repression of rhotekin 2 (RTKN2), an oxysterol stress responder, to optimize cell survival. A palmitate-rich diet, which increases serum 27OHC, or APP ablation, abrogated this response in vivo. Further, this pathway was downregulated in human Alzheimer's Disease (AD) brains but not in frontotemporal dementia brains. These results unveil MAST4 as functional kinase of FOXO1 in a 27OHC AICD-driv...

Frontiers in Cellular Neuroscience, 2015

Journal of Healthcare Engineering, 2010

Communications in Nonlinear Science and Numerical Simulation, Mar 1, 2016

Developmental cell, Jan 8, 2014

Distinct pools of the bone morphogenetic protein (BMP) Glass bottom boat (Gbb) control structure ... more Distinct pools of the bone morphogenetic protein (BMP) Glass bottom boat (Gbb) control structure and function of the Drosophila neuromuscular junction. Specifically, motoneuron-derived Gbb regulates baseline neurotransmitter release, whereas muscle-derived Gbb regulates neuromuscular junction growth. Yet how cells differentiate between these ligand pools is not known. Here we present evidence that the neuronal Gbb-binding protein Crimpy (Cmpy) permits discrimination of pre- and postsynaptic ligand by serving sequential functions in Gbb signaling. Cmpy first delivers Gbb to dense core vesicles (DCVs) for activity-dependent release from presynaptic terminals. In the absence of Cmpy, Gbb is no longer associated with DCVs and is not released by activity. Electrophysiological analyses demonstrate that Cmpy promotes Gbb's proneurotransmission function. Surprisingly, the Cmpy ectodomain is itself released upon DCV exocytosis, arguing that Cmpy serves a second function in BMP signaling....

Anatomical record (Hoboken, N.J. : 2007), Jan 12, 2018

The autonomic brainstem generates breathing rhythm by integrating inputs from chemo- and mechanos... more The autonomic brainstem generates breathing rhythm by integrating inputs from chemo- and mechanosensors in the viscera and coordinating descending outputs from higher structures in the central nervous system. Hypoglossal motoneurons (XII MNs) receive inputs from respiratory premotor neurons, important for maintaining airway patency. Previous studies in rodents report significant changes in breathing control during the first three weeks of life, with a sensitive period at 10 to 13 days post-birth (P10-P13) characterized by pronounced changes in neurotransmitters, excitation-inhibition balance, and breathing physiology. However, age-dependent morphological changes of XII MNs during the first three weeks post-birth and especially this sensitive period are under-studied. Here, we comprehensively characterize and quantify the early morphological changes in rat XII MNs. We hypothesized that morphological changes in XII MNs correspond to the functionally-defined sensitive period observed a...

Journal of inflammation research, 2018

In this review, we provide an overview of the US Food and Drug Administration (FDA)-approved clin... more In this review, we provide an overview of the US Food and Drug Administration (FDA)-approved clinical uses of vagus nerve stimulation (VNS) as well as information about the ongoing studies and preclinical research to expand the use of VNS to additional applications. VNS is currently FDA approved for therapeutic use in patients aged >12 years with drug-resistant epilepsy and depression. Recent studies of VNS in in vivo systems have shown that it has anti-inflammatory properties which has led to more preclinical research aimed at expanding VNS treatment across a wider range of inflammatory disorders. Although the signaling pathway and mechanism by which VNS affects inflammation remain unknown, VNS has shown promising results in treating chronic inflammatory disorders such as sepsis, lung injury, rheumatoid arthritis (RA), and diabetes. It is also being used to control pain in fibromyalgia and migraines. This new preclinical research shows that VNS bears the promise of being applied...

American journal of physiology. Regulatory, integrative and comparative physiology, Jan 22, 2017

Long-term hypoxia (LTH) has a profound effect on pulmonary arterial vasoconstriction in the fetus... more Long-term hypoxia (LTH) has a profound effect on pulmonary arterial vasoconstriction in the fetus and adult. Dysregulation in Ca2+ signaling is important during the development of LTH induced pulmonary hypertension. In the present study we tested the hypothesis that L-type Ca2+ channels, which are voltage-dependent and found in smooth, skeletal, and cardiac muscle, are important in the adaptation of pulmonary arterial contractions in post-natal maturation and in response to LTH. Pulmonary arteries were isolated from fetal or adult sheep maintained at low- or high-altitude (3,801 m) for >100 days. The effects of a L-type Ca2+ channel opener FPL 64176 (FPL) in the presence or absence of an inhibitor Nifedipine (NIF) on arterial contractions, intracellular Ca2+ oscillations, and ryanodine receptor-driven Ca2+ sparks were measured. FPL induced pulmonary arterial contractions in all groups that were sensitive to NIF. However, when compared to 125 mM K+, FPL contractions were greater i...

Pediatric research, Jan 20, 2017

BackgroundVagus Nerve Stimulation (VNS) is an FDA-approved method delivering electrical impulses ... more BackgroundVagus Nerve Stimulation (VNS) is an FDA-approved method delivering electrical impulses for treatment of depression and epilepsy in adults. The vagus nerve innervates the majority of visceral organs and cervix, but potential impacts of VNS on the progress of pregnancy and the fetus are not well studied.MethodsWe tested the hypothesis that VNS in pregnant dams does not induce inflammatory changes in the cardiorespiratory control regions of the pups' brainstem, potentially impacting the morbidity and mortality of offspring. Pregnant dams were implanted with stimulators providing intermittent low or high frequency electrical stimulation of the sub-diaphragmatic esophageal segment of the vagus nerve for 6-7 days until delivery. After birth, we collected pup brainstems that included cardio-respiratory control regions and counted the cells labeled for pro-inflammatory cytokines (IL-1β, IL-6, TNFα) and HMGB1.ResultsNeither pup viability nor number of cells labeled for pro-infl...

American journal of respiratory and critical care medicine, Jan 15, 2015

Respiratory physiology & neurobiology, 2015

We investigated whether pre-treatment with neonatal sustained hypoxia (SH) prior to chronic inter... more We investigated whether pre-treatment with neonatal sustained hypoxia (SH) prior to chronic intermittent hypoxia (SH+CIH) would modify in vitro carotid body (CB) chemoreceptor activity and the excitability of neurons in the caudal nucleus of the solitary tract (nTS). Sustained hypoxia followed by CIH exposure simulates an oxygen paradigm experienced by extremely premature infants who developed persistent apnea. Rat pups were treated with 5 days of SH (11% O2) from postnatal age 1 (P1) followed by 10 days of subsequent chronic intermittent hypoxia (CIH, 5% O2/5 min, 8 h/day, between P6 and P15) as described previously (Mayer et al., Respir. Physiol. Neurobiol. 187(2): 167-75, 2013). At the end of SH+CIH exposure (P16), basal firing frequency was enhanced, and the hypoxic sensory response of single unit CB chemoafferents was attenuated. Further, basal firing frequency and the amplitude of evoked excitatory post-synaptic currents (ESPC's) of nTS neurons was augmented compared to ag...

Neonatology, 2010

Preterm infants are subject to fluctuations in blood gas status associated with immature respirat... more Preterm infants are subject to fluctuations in blood gas status associated with immature respiratory control. Intermittent hypoxia during early postnatal life has been shown to increase chemoreceptor sensitivity and destabilize the breathing pattern; however, intermittent hypercapnia remains poorly studied. Therefore, to test the hypothesis that intermittent hypercapnia results in altered respiratory control, we examined the effects of daily exposure to intermittent hypercapnia on the ventilatory response to subsequent hypercapnic and hypoxic exposure in neonatal rat pups. Exposure cycles consisted of 5 min of intermittent hypercapnia (5% CO(2), 21% O(2), balance N(2)) followed by 10 min of normoxia. Rat pups were exposed to 18 exposure cycles each day for 1 week, from postnatal day 7 to 14. We analyzed diaphragm electromyograms (EMGs) from pups exposed to subsequent acute hypercapnic (5% CO(2)) and hypoxic (12% O(2)) challenges. In response to a subsequent hypercapnia challenge, th...