Reduced Extracellular Dopamine and Increased Responsiveness to Novelty: Neurochemical and Behavioral Sequelae of Intermittent Hypoxia

Decker, Michael J.; Jones, Karra A.; Solomon, Inez G.; Keating, Glenda L.; Rye, David B.

doi:10.1093/sleep/28.2.169

Cited by 65 publications

(46 citation statements)

References 41 publications

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“…In animal models of sleep apnea oxygenation, repeated hypoxia/reoxygenation events result in wake impairments (Decker et al, 2003(Decker et al, , 2005Veasey et al, 2004a;Zhan et al, 2005a,b). The residual wake impairments, after hypoxia/reoxygenation exposure, are associated with oxidative injury (e.g., lipid peroxidation, nitration, and protein carbonylation) in several brain regions, including wake-active regions (Veasey et al, 2004a,b;Zhan et al, 2005a,b).…”

Section: Introductionmentioning

confidence: 99%

Selective Loss of Catecholaminergic Wake–Active Neurons in a Murine Sleep Apnea Model

Zhu¹,

Fenik²,

Zhan³

et al. 2007

J. Neurosci.

164

117

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The presence of refractory wake impairments in many individuals with severe sleep apnea led us to hypothesize that the hypoxia/ reoxygenation events in sleep apnea permanently damage wake-active neurons. We now confirm that long-term exposure to hypoxia/ reoxygenation in adult mice results in irreversible wake impairments. Functionality and injury were next assessed in major wake-active neural groups. Hypoxia/reoxygenation exposure for 8 weeks resulted in vacuolization in the perikarya and dendrites and markedly impaired c-fos activation response to enforced wakefulness in both noradrenergic locus ceruleus and dopaminergic ventral periaqueductal gray wake neurons. In contrast, cholinergic, histaminergic, orexinergic, and serotonergic wake neurons appeared unperturbed. Six month exposure to hypoxia/reoxygenation resulted in a 40% loss of catecholaminergic wake neurons. Having previously identified NADPH oxidase as a major contributor to wake impairments in hypoxia/reoxygenation, the role of NADPH oxidase in catecholaminergic vulnerability was next addressed. NADPH oxidase catalytic and cytosolic subunits were evident in catecholaminergic wake neurons, where hypoxia/reoxygenation resulted in translocation of p67 phox to mitochondria, endoplasmic reticulum, and membranes. Treatment with a NADPH oxidase inhibitor, apocynin, throughout hypoxia/reoxygenation exposures conferred protection of catecholaminergic neurons. Collectively, these data show that select wake neurons, specifically the two catecholaminergic groups, can be rendered persistently impaired after long-term exposure to hypoxia/reoxygenation, modeling sleep apnea; wake impairments are irreversible; catecholaminergic neurons are lost; and neuronal NADPH oxidase contributes to this injury. It is anticipated that severe obstructive sleep apnea in humans destroys catecholaminergic wake neurons.

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Section: Introductionmentioning

confidence: 99%

Selective Loss of Catecholaminergic Wake–Active Neurons in a Murine Sleep Apnea Model

Zhu¹,

Fenik²,

Zhan³

et al. 2007

J. Neurosci.

164

117

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“…5 Hypoxia is also widely discussed to have a role in the demyelination of axons in MS 6 and to decrease the dopaminergic activity. 7 Finally, hypoxia is known to occur after cell transplantation and to affect eminently the survival of the implanted cells in the first critical posttransplantational phase. Hypoxic preconditioning of stem cells before transplantation may improve the survival and therapeutic effects of implanted cells.…”

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confidence: 99%

Survival, neuron-like differentiation and functionality of mesenchymal stem cells in neurotoxic environment: the critical role of erythropoietin

et al. 2009

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Mesenchymal stem cells (MSCs) can ameliorate symptoms in several neurodegenerative diseases. However, the toxic environment of a degenerating central nervous system (CNS) characterized by hypoxia, glutamate (Glu) excess and amyloid beta (Abeta) pathology may hamper the survival and regenerative/replacing capacities of engrafted stem cells. Indeed, human MSC (hMSC) exposed to hypoxia were disabled in (i) the capacity of their muscarinic receptors (mAChRs) to respond to acetylcholine (ACh) with a transient increase in intracellular [Ca 2 þ ], (ii) their capacity to metabolize Glu, reflected by a strong decrease in glutamine synthetase activity, and (iii) their survival on exposure to Glu. Cocultivation of MSC with PC12 cells expressing the amyloid precursor protein gene (APPsw-PC12) increased the release of IL-6 from MSC. HMSC exposed to erythropoietin (EPO) showed a cholinergic neuron-like phenotype reflected by increased cellular levels of choline acetyltransferase, ACh and mAChR. All their functional deficits observed under hypoxia, Glu exposure and APPsw-PC12 cocultivation were reversed by the application of EPO, which increased the expression of Wnt3a. EPO also enhanced the metabolism of Abeta in MSC by increasing their neprilysin content. Our data show that cholinergic neuron-like differentiation of MSC, their functionality and resistance to a neurotoxic environment is regulated and can be improved by EPO, highlighting its potential for optimizing cellular therapies of the CNS.

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“…Administration of psychostimulants such as amphetamine induced hyperactivity by increasing the release of dopamine (Rowley et al, 2012). In addition, hyperactivity in the home cage during the dark phase was correlated with an elevation in dopamine levels in the striatum (Decker et al, 2005). Perinatal and subchronic exposure to some PCB congeners and OH-PCB 106 induced alterations in the dopaminergic nervous system in rodents (Caudle et al, 2006;Faroon et al, 2000;Lee et al, 2012;Lesmana et al, 2014;Seegal et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Differential neurotoxic effects of <i>in utero</i> and lactational exposure to hydroxylated polychlorinated biphenyl (OH-PCB 106) on spontaneous locomotor activity and motor coordination in young adult male mice

et al. 2017

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-We investigated whether in utero or lactational exposure to 4-hydroxy-2',3,3',4',5'-pentachlorobiphenyl (OH-PCB 106) affects spontaneous locomotor activity and motor coordination in young adult male mice. For in utero exposure, pregnant C57BL/6J mice received 0.05 or 0.5 mg/kg body weight of OH-PCB 106 or corn oil vehicle via gavage every second day from gestational day 10 to 18. For lactational exposure, the different groups of dams received 0.05 or 0.5 mg/kg body weight of OH-PCB 106 or corn oil vehicle via gavage every second day from postpartum day 3 to 13. At 6-7 weeks of age, the spontaneous locomotor activities of male offspring were evaluated for a 24-hr continuous session in a home cage and in an open field for 30-min. Motor coordination function on an accelerating rotarod was also measured. Mice exposed prenatally to OH-PCB 106 showed increased spontaneous locomotor activities during the dark phase in the home cage and during the first 10-min in the open field compared with control mice. Mice exposed lactationally to OH-PCB 106, however, did not show a time-dependent decrease in locomotor activity in the open field. Instead, their locomotor activity increased significantly during the second 10-min block. In addition, mice exposed lactationally to OH-PCB 106 displayed impairments in motor coordination in the rotarod test. These results suggest that perinatal exposure to OH-PCB 106 affects motor behaviors in young adult male mice. Depending on the period of exposure, OH-PCB 106 may have different effects on neurobehavioral development.

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Reduced Extracellular Dopamine and Increased Responsiveness to Novelty: Neurochemical and Behavioral Sequelae of Intermittent Hypoxia

Cited by 65 publications

References 41 publications

Selective Loss of Catecholaminergic Wake–Active Neurons in a Murine Sleep Apnea Model

Selective Loss of Catecholaminergic Wake–Active Neurons in a Murine Sleep Apnea Model

Survival, neuron-like differentiation and functionality of mesenchymal stem cells in neurotoxic environment: the critical role of erythropoietin

Differential neurotoxic effects of <i>in utero</i> and lactational exposure to hydroxylated polychlorinated biphenyl (OH-PCB 106) on spontaneous locomotor activity and motor coordination in young adult male mice

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