Sigma Receptor Ligand, (+)-Pentazocine, Suppresses Inflammatory Responses of Retinal Microglia

Zhao, Jing; Ha, Yonju; Liou, Gregory I.; Gonsalvez, Graydon B.; Smith, Sylvia B.; Bollinger, Kathryn E.

doi:10.1167/iovs.13-12823

Cited by 56 publications

(62 citation statements)

References 43 publications

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“…The robust rescue of cone function in rd10 mice treated with (+)-PTZ appears to be attributable (at least in part) to attenuated Müller cell gliosis, reduced microglial activation, and decreased oxidative stress. Sig1R, whose activation also has been reported to attenuate excitotoxicity (13,18), calcium dysregulation (12,17,26), ER stress (12,23,32), and inflammation (15,16,35), constitutes a promising target for pharmacologically treating retinal disease.…”

Section: Discussionmentioning

confidence: 99%

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Activation of the molecular chaperone, sigma 1 receptor, preserves cone function in a murine model of inherited retinal degeneration

Wang

Saul

Roon

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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119

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Retinal degenerative diseases are major causes of untreatable blindness, and novel approaches to treatment are being sought actively. Here we explored the activation of a unique protein, sigma 1 receptor (Sig1R), in the treatment of PRC loss because of its multifaceted role in cellular survival. We used Pde6β rd10 (rd10) mice, which harbor a mutation in the rod-specific phosphodiesterase gene Pde6β and lose rod and cone photoreceptor cells (PRC) within the first 6 wk of life, as a model for severe retinal degeneration. Systemic administration of the high-affinity Sig1R ligand (+)-pentazocine [(+)-PTZ] to rd10 mice over several weeks led to the rescue of cone function as indicated by electroretinographic recordings using natural noise stimuli and preservation of cone cells upon spectral domain optical coherence tomography and retinal histological examination. The protective effect appears to result from the activation of Sig1R, because rd10/Sig1R

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Section: Discussionmentioning

confidence: 99%

“…Sig1R ligands suppress ROS production in multiple cell types (23,(32)(33)(34) and inhibit inflammatory cytokine release (16,35). Oxidative stress increases in models of PRC degeneration (36), and antioxidant treatment delays PRC death (4).…”

mentioning

confidence: 99%

Activation of the molecular chaperone, sigma 1 receptor, preserves cone function in a murine model of inherited retinal degeneration

Wang

Saul

Roon

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

119

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“…In fact, HMGB1 has been shown to increase via sigma-1 receptors in cultured astrocytes treated with methamphetamine (Zhang et al, 2015). Stimulation of sigma-1 receptors is thought to activate microglia, and perhaps astrocytes, to initiate both proinflammatory and anti-inflammatory responses (Gardner et al, 2004; Gekker et al, 2006; Yao et al, 2011; Zhao et al, 2014). Lastly, there is some evidence to suggest that psychostimulants activate TLRs expressed on glial cells (Liao et al, 2016; Northcutt et al, 2015).…”

Section: Drugs Of Abuse and Glial Cell Activitymentioning

confidence: 99%

Glial and neuroinflammatory targets for treating substance use disorders

Bachtell

Jones

Heinzerling

et al. 2017

Drug and Alcohol Dependence

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Background The plenary session at the 2016 Behavior, Biology and Chemistry: Translational Research in Addiction Conference focused on glia as potential players in the development, persistence and treatment of substance use disorders. Glia partake in various functions that are important for healthy brain activity. Drugs of abuse alter glial cell activity producing several perturbations in brain function that are thought to contribute to behavioral changes associated with substance use disorders. Consequently, drug-induced changes in glia-driven processes in the brain represent potential targets for pharmacotherapeutics treating substance use disorders. Methods Four speakers presented preclinical and clinical research illustrating the effects that glial modulators have on abuse-related behavioral effects of psychostimulants and opioids. This review highlights some of these findings and expands its focus to include other research focused on drug-induced glia abnormalities and glia-focused treatment approaches in substance use disorders. Results Preclinical findings show that drugs of abuse induce neuroinflammatory signals and disrupt glutamate homeostasis through their interaction with microglia and astrocytes. Preclinical and clinical studies testing the effects of glial modulators show general effectiveness in reducing behaviors associated with substance use disorders. Conclusions The contribution of drug-induced glial activity continues to emerge as an intriguing target for substance use disorder treatments. Clinical investigations of glial modulators have yielded promising results on substance use measures and indicate that they are generally safe and well-tolerated. However, results have not been entirely positive and more questions remain for continued exploration in the development and testing of glial-directed treatments for substance use disorders.

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“…For detecting the neuronal death after PRE-084 treatment in TBI model, FJB staining procedures were conducted at 3 days as previously described (Zhao et al 2014). Briefly, the sections were transferred to a solution of 0.06 % potassium permanganate for 30 min, then rinsed with dH 2 O, followed by a 0.0004 % F-J B (Histochem, Jefferson, AR, USA) staining solution for 45 min.…”

Section: Fluoro-jade B (Fjb) Stainingmentioning

confidence: 99%

Sigma-1 Receptor Modulates Neuroinflammation After Traumatic Brain Injury

Dong

Ren

et al. 2015

Cell Mol Neurobiol

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Traumatic brain injury (TBI) remains a significant clinical problem and contributes to one-third of all injury-related deaths. Activated microglia-mediated inflammatory response is a distinct characteristic underlying pathophysiology of TBI. Here, we evaluated the effect and possible mechanisms of the selective Sigma-1 receptor agonist 2-(4-morpholinethyl)-1-phenylcyclohexanecarboxylate (PRE-084) in mice TBI model. A single intraperitoneal injection 10 μg/g PRE-084, given 15 min after TBI significantly reduced lesion volume, lessened brain edema, attenuated modified neurological severity score, increased the latency time in wire hang test, and accelerated body weight recovery. Moreover, immunohistochemical analysis with Iba1 staining showed that PRE-084 lessened microglia activation. Meanwhile, PRE-084 reduced nitrosative and oxidative stress to proteins. Thus, Sigma-1 receptors play a major role in inflammatory response after TBI and may serve as useful target for TBI treatment in the future.

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Sigma Receptor Ligand, (+)-Pentazocine, Suppresses Inflammatory Responses of Retinal Microglia

Abstract: Treatment with (+)-pentazocine suppressed inflammatory responses of retinal microglia and inhibited LPS-induced activation of ERK/JNK MAPK. In neurodegenerative disease, (+)-pentazocine may exert neuroprotective effects through manipulation of microglia.

Cited by 56 publications

References 43 publications

Activation of the molecular chaperone, sigma 1 receptor, preserves cone function in a murine model of inherited retinal degeneration

Activation of the molecular chaperone, sigma 1 receptor, preserves cone function in a murine model of inherited retinal degeneration

Glial and neuroinflammatory targets for treating substance use disorders

Sigma-1 Receptor Modulates Neuroinflammation After Traumatic Brain Injury

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