Cell-specific loss of κ-opioid receptors in oligodendrocytes of the dysmyelinating jimpy mouse

Knapp, Pamela E.; Adjan, Valeriya V.; Hauser, Kurt F.

doi:10.1016/j.neulet.2008.12.022

Cited by 14 publications

(3 citation statements)

References 50 publications

(64 reference statements)

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“…Nor-BNI greatly enhanced glutamate-induced death of oligodendroglia while causing only modest effects on its own, again invoking the issue of context in opiate effects on survival as well as growth/differentiation ( 165 ). A relationship between KOR and oligodendrocyte function/myelin production was also suggested by our finding that KOR (but not MOR) was severely reduced on oligodendrocytes, but not neurons, in the jimpy mouse, a dysmyelinating mutant ( 205 ). More recent work has also shown that KOR agonists, including U50,488, can promote differentiation/myelination in human oligodendrocytes derived from immortalized pluripotent stem cells ( 206 ).…”

Section: Oligodendrocytessupporting

confidence: 62%

Opiate Drugs with Abuse Liability Hijack the Endogenous Opioid System to Disrupt Neuronal and Glial Maturation in the Central Nervous System

Hauser

Knapp

2018

Front. Pediatr.

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The endogenous opioid system, comprised of multiple opioid neuropeptide and receptor gene families, is highly expressed by developing neural cells and can significantly influence neuronal and glial maturation. In many central nervous system (CNS) regions, the expression of opioid peptides and receptors occurs only transiently during development, effectively disappearing with subsequent maturation only to reemerge under pathologic conditions, such as with inflammation or injury. Opiate drugs with abuse liability act to modify growth and development by mimicking the actions of endogenous opioids. Although typically mediated by μ-opioid receptors, opiate drugs can also act through δ- and κ-opioid receptors to modulate growth in a cell-type, region-specific, and developmentally regulated manner. Opioids act as biological response modifiers and their actions are highly contextual, plastic, modifiable, and influenced by other physiological processes or pathophysiological conditions, such as neuro-acquired immunodeficiency syndrome. To date, most studies have considered the acute effects of opiates on cellular maturation. For example, activating opioid receptors typically results in acute growth inhibition in both neurons and glia. However, with sustained opioid exposure, compensatory factors become operative, a concept that has been largely overlooked during CNS maturation. Accordingly, this article surveys prior studies on the effects of opiates on CNS maturation, and also suggests new directions for future research in this area. Identifying the cellular and molecular mechanisms underlying the adaptive responses to chronic opiate exposure (e.g., tolerance) during maturation is crucial toward understanding the consequences of perinatal opiate exposure on the CNS.

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Section: Oligodendrocytessupporting

confidence: 62%

Opiate Drugs with Abuse Liability Hijack the Endogenous Opioid System to Disrupt Neuronal and Glial Maturation in the Central Nervous System

Hauser

Knapp

2018

Front. Pediatr.

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“…Chronic oxycodone exposure in rats causes some axonopathies and reduces the size of axonal fascicles, decreases myelin basic protein levels, and causes the accumulation of amyloid-β precursor protein (APP) (Fan et al 2018). Most preclinical studies have examined the effects of opioids and opioid receptor blockade on OL maturation and/or the timing of myelination (Hauser et al 1993;Knapp et al 1998;Stiene-Martin et al 2001;Sanchez et al 2008;Knapp et al 2009;Vestal-Laborde et al 2014). OLs can transiently express MORs and other opioid receptor types (Knapp et al 1998;Tryoen-Toth et al 2000;Knapp et al 2001;Stiene-Martin et al 2001).…”

Section: White Matter/oligodendroglial Pathologymentioning

confidence: 99%

Opioid and neuroHIV Comorbidity – Current and Future Perspectives

Fitting

McRae

Hauser

2020

J Neuroimmune Pharmacol

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With the current national opioid crisis, it is critical to examine the mechanisms underlying pathophysiologic interactions between human immunodeficiency virus (HIV) and opioids in the central nervous system (CNS). Recent advances in experimental models, methodology, and our understanding of disease processes at the molecular and cellular levels reveal opioid-HIV interactions with increasing clarity. However, despite the substantial new insight, the unique impact of opioids on the severity, progression, and prognosis of neuroHIV and HIV-associated neurocognitive disorders (HAND) are not fully understood. In this review, we explore, in detail, what is currently known about mechanisms underlying opioid interactions with HIV, with emphasis on individual HIV-1-expressed gene products at the molecular, cellular and systems levels. Furthermore, we review preclinical and clinical studies with a focus on key considerations when addressing questions of whether opioid-HIV interactive pathogenesis results in unique structural or functional deficits not seen with either disease alone. These considerations include, understanding the combined consequences of HIV-1 genetic variants, host variants, and μ-opioid receptor (MOR) and HIV chemokine co-receptor interactions on the comorbidity. Lastly, we present topics that need to be considered in the future to better understand the unique contributions of opioids to the pathophysiology of neuroHIV. Graphical Abstract Blood-brain barrier and the neurovascular unit. With HIV and opiate co-exposure (represented below the dotted line), there is breakdown of tight junction proteins and increased leakage of paracellular compounds into the brain. Despite this, opiate exposure selectively increases the expression of some efflux transporters, thereby restricting brain penetration of specific drugs.

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“…The 158N and 158JP cell lines were derived from normal and Jimpy mice, respectively, and display features of well-differentiated oligodendrocytes [21]. A mutation in the proteolipid protein PLP/DM20 in Jimpy mice causes premature death of oligodendrocytes and leads to severe CNS demyelination [22]. In comparison to 158N cells, 158JP cells were observed to have significantly higher spontaneous ROS at baseline [21].…”

Section: Cell Culture and Experimental Conditionsmentioning

confidence: 99%

N-acetylcysteine Provides Cytoprotection in Murine Oligodendrocytes through Heme Oxygenase-1 Activity

et al. 2020

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Oligodendrocytic injury by oxidative stress can lead to demyelination, contributing to neurodegeneration. We investigated the mechanisms by which an antioxidant, N-acetylcysteine (NAC), reduces oxidative stress in murine oligodendrocytes. We used normal 158N and mutant 158JP cells with endogenously high reactive oxygen species (ROS) levels. Oxidative stress was induced in 158N cells using hydrogen peroxide (H2O2, 500 μM), and both cells were treated with NAC (50 µM to 500 µM). ROS production, total glutathione (GSH) and cell survival were measured 24 h after treatment. In normal cells, H2O2 treatment resulted in a ~5.5-fold increase in ROS and ~50% cell death. These deleterious effects of oxidative stress were attenuated by NAC, resulting in improved cell survival. Similarly, NAC treatment resulted in decreased ROS levels in 158JP cells. Characterization of mechanisms underlying cytoprotection in both cell lines revealed an increase in GSH levels by NAC, which was partially blocked by an inhibitor of GSH synthesis. Interestingly, we observed heme oxygenase-1 (HO-1), a cytoprotective enzyme, play a critical role in cytoprotection. Inhibition of HO-1 activity abolished the cytoprotective effect of NAC with a corresponding decrease in total antioxidant capacity. Our results indicate that NAC promotes oligodendrocyte survival in oxidative stress-related conditions through multiple pathways.

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Cell-specific loss of κ-opioid receptors in oligodendrocytes of the dysmyelinating jimpy mouse

Cited by 14 publications

References 50 publications

Opiate Drugs with Abuse Liability Hijack the Endogenous Opioid System to Disrupt Neuronal and Glial Maturation in the Central Nervous System

Opiate Drugs with Abuse Liability Hijack the Endogenous Opioid System to Disrupt Neuronal and Glial Maturation in the Central Nervous System

Opioid and neuroHIV Comorbidity – Current and Future Perspectives

N-acetylcysteine Provides Cytoprotection in Murine Oligodendrocytes through Heme Oxygenase-1 Activity

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