Activation of the sigma-1 receptor by haloperidol metabolites facilitates brain-derived neurotrophic factor secretion from human astroglia

Dalwadi, Dhwanil A.; Kim, Seong-Cheol; Schetz, John A.

doi:10.1016/j.neuint.2017.02.003

Cited by 17 publications

(21 citation statements)

References 91 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results showed that stimulation of S1R with (+)-PTZ increased ONH astrocyte secretion of total BDNF with a corresponding increase of proBDNF protein within ONH astrocyte cell lysates. This finding is in accord with a recent study showing that S1R agonists stimulate the release of BDNF from a human astrocyte cell line (Dalwadi et al, 2017). S1R has the potential to mediate BDNF secretion via multiple mechanisms.…”

Section: 0 Discussionsupporting

confidence: 93%

Relationship between Sigma-1 receptor and BDNF in the visual system

Mysona

Zhao

Smith

et al. 2018

Experimental Eye Research

View full text Add to dashboard Cite

Glaucoma is an incurable optic neuropathy characterized by dysfunction and death of retinal ganglion cells (RGCs). Brain derived neurotrophic factor (BDNF) is an essential neurotrophin that supports RGC function and survival. Despite BDNF's importance, our knowledge of molecular mechanisms that modulate BDNF processing and secretion is incomplete. Sigma-1 receptor (S1R) is associated with increased BDNF in hippocampus and with BDNF secretion by brain-derived astrocytes and neuronal cell lines. Much less is known about the relationship between S1R and BDNF in the visual system. Here, we examine how S1R activation and deletion alter expression of mature BDNF (mBDNF) and proBDNF in retina and cultured optic nerve head (ONH) astrocytes. For S1R activation, the S1R agonist (+)-pentazocine (PTZ, 0.5 mg/kg) was administered by intraperitoneal injection to C57BL/6J mice, 3 times per week, for 5 weeks. Expression of proBDNF and mBDNF was also examined in S1R knockout and age-matched C57BL/6J mice. In vitro, cultured ONH astrocytes were treated with 3 μM PTZ for 24 h followed by collection of media and ONH astrocyte lysates. Results showed that treatment with (+)-PTZ increased mBDNF protein in both retina and hippocampus. In contrast, S1R deletion was associated with retinal mBDNF deficits. In ONH astrocytes S1R agonist (+)-PTZ significantly increased levels of secreted BDNF and proBDNF in cell lysates. These findings support a role for S1R in the modulation of BDNF levels within the retina and optic nerve head. Treatment with S1R agonists might provide benefit in diseases such as glaucoma by increasing BDNF levels from endogenous sources.

show abstract

Section: 0 Discussionsupporting

confidence: 93%

Relationship between Sigma-1 receptor and BDNF in the visual system

Mysona

Zhao

Smith

et al. 2018

Experimental Eye Research

View full text Add to dashboard Cite

show abstract

“…Consistently, two metabolites of haloperidol (reduced haloperidol) that act as functionally selective Sig-1R agonists stimulate human astrocytes to secret BDNF. (Dalwadi et al, 2017 ). In support, we recently found that SKF83959, a recent identified Sig-1R allosteric modulator (Guo et al, 2013 ), elicited rapidly antidepressant effects via stimulating BDNF production (Wang et al, 2016 ).…”

Section: Sigma-1 Receptors and Astrocytesmentioning

confidence: 99%

Sigma-1 Receptor-Modulated Neuroinflammation in Neurological Diseases

Jia

Cheng

Wang

et al. 2018

Front. Cell. Neurosci.

View full text Add to dashboard Cite

A large body of evidence indicates that sigma-1 receptors (Sig-1R) are important drug targets for a number of neuropsychiatric disorders. Sig-1Rs are enriched in central nervous system (CNS). In addition to neurons, both cerebral microglia and astrocytes express Sig-1Rs. Activation of Sig-1Rs is known to elicit potent neuroprotective effects and promote neuronal survival via multiple mechanisms, including promoting mitochondrial functions, decreasing oxidative stress and regulating neuroimmnological functions. In this review article, we focus on the emerging role of Sig-1Rs in regulating neuroinflammation and discuss the recent advances on the Sig-1R-modulating neuroinflammation in the pathophysiology and therapy of neurodegenerative disorders.

show abstract

“…(+)-SKF-10.047 BDNF Increases BDNF secretion in vitro. The effect was blocked by Sigma1R antagonist BD-1063 [162].…”

Section: Epigenetic Regulation Of Gene Expressionmentioning

confidence: 96%

Chaperone Sigma1R and Antidepressant Effect

Voronin

Vakhitova

Seredenin

2020

IJMS

View full text Add to dashboard Cite

This review analyzes the current scientific literature on the role of the Sigma1R chaperone in the pathogenesis of depressive disorders and pharmacodynamics of antidepressants. As a result of ligand activation, Sigma1R is capable of intracellular translocation from the endoplasmic reticulum (ER) into the region of nuclear and cellular membranes, where it interacts with resident proteins. This unique property of Sigma1R provides regulation of various receptors, ion channels, enzymes, and transcriptional factors. The current review demonstrates the contribution of the Sigma1R chaperone to the regulation of molecular mechanisms involved in the antidepressant effect.

show abstract

Activation of the sigma-1 receptor by haloperidol metabolites facilitates brain-derived neurotrophic factor secretion from human astroglia

Cited by 17 publications

References 91 publications

Relationship between Sigma-1 receptor and BDNF in the visual system

Relationship between Sigma-1 receptor and BDNF in the visual system

Sigma-1 Receptor-Modulated Neuroinflammation in Neurological Diseases

Chaperone Sigma1R and Antidepressant Effect

Contact Info

Product

Resources

About