Immunohistochemical localization of the σ1-receptor in oligodendrocytes in the rat central nervous system

Palacios, G.; Muro, Anna; Vela, José Miguel; Molina‐Holgado, Eduardo; Guitart, Xavier; Ovalle, Sergio; Zamanillo, Daniel

doi:10.1016/s0006-8993(02)03892-1

Cited by 56 publications

(37 citation statements)

References 35 publications

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“…Sigma-1 receptors are strongly upregulated in the corpus callosum of developing brains, particularly in the phase of active myelination [37]. A high expression of these binding sites is observed in oligodendrocytes [127] and Schwann cells [128], suggesting involvement of the sigma-1 receptor in myelination. Knockdown of these receptors by siRNA results in complete inhibition of the differentiation and myelination of oligodendrocyte progenitor cells [37] and prevention of the formation of mature dendritic spines in hippocampal primary neurons [149].…”

Section: Involvement Of Sigma-1 Receptors In Neuronal Differentiationmentioning

confidence: 99%

The cholinergic system, sigma-1 receptors and cognition

Waarde

Ramakrishnan

Rybczynska

et al. 2011

Behavioural Brain Research

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a b s t r a c tThis article provides an overview of present knowledge regarding the relationship between the cholinergic system and sigma-1 receptors, and discusses potential applications of sigma-1 receptor agonists in the treatment of memory deficits and cognitive disorders. Sigma-1 receptors, initially considered as a subtype of the opioid family, are unique ligand-regulated molecular chaperones in the endoplasmatic reticulum playing a modulatory role in intracellular calcium signaling and in the activity of several neurotransmitter systems, particularly the cholinergic and glutamatergic pathways. Several central nervous system (CNS) drugs show high to moderate affinities for sigma-1 receptors, including acetylcholinesterase inhibitors (donepezil), antipsychotics (haloperidol, rimcazole), selective serotonin reuptake inhibitors (fluvoxamine, sertraline) and monoamine oxidase inhibitors (clorgyline). These compounds can influence cognitive functions both via their primary targets and by activating sigma-1 receptors in the CNS. Sigma-1 agonists show powerful anti-amnesic and neuroprotective effects in a large variety of animal models of cognitive dysfunction involving, among others (i) pharmacologic target blockade (with muscarinic or NMDA receptor antagonists or p-chloroamphetamine); (ii) selective lesioning of cholinergic neurons; (iii) CNS administration of ␤-amyloid peptides; (iv) aging-induced memory loss, both in normal and senescentaccelerated rodents; (v) neurodegeneration induced by toxic compounds (CO, trimethyltin, cocaine), and (vi) prenatal restraint stress.

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Section: Involvement Of Sigma-1 Receptors In Neuronal Differentiationmentioning

confidence: 99%

The cholinergic system, sigma-1 receptors and cognition

Waarde

Ramakrishnan

Rybczynska

et al. 2011

Behavioural Brain Research

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“…Sig-1Rs are highly expressed in oligodendrocytes of rat brains (32,33). We previously demonstrated that Sig-1Rs colocalize with GalCer at the ER and up-regulate in oligodendrocyte-type 2 astrocyte progenitors during their oligodendrocyte differentiation (33).…”

mentioning

confidence: 93%

The Lifetime of UDP-galactose:Ceramide Galactosyltransferase Is Controlled by a Distinct Endoplasmic Reticulum-associated Degradation (ERAD) Regulated by Sigma-1 Receptor Chaperones

Hayashi

Fujimoto

et al. 2012

Journal of Biological Chemistry

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Background: UDP-galactose:ceramide galactosyltransferase (CGalT) is a glycoprotein that synthesizes galactosylceramides at the endoplasmic reticulum (ER). Results: Molecular chaperone sigma-1 receptors promote degradation of CGalT by forming a complex with Insig. Conclusion: CGalT and its activity are post-translationally regulated by ER-associated degradation (ERAD) involving sigma-1 receptor chaperones. Significance: The sterol-sensing ERAD system controls the enzyme involved in glycosphingolipid biosynthesis.

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“…The sigma-1R is a transmembrane protein found in the endoplasmic reticulum [6,7], which is highly expressed in MNs and other cells in the spinal cord [6,[8][9][10]. This receptor has the ability to translocate from the endoplasmic reticulum to the plasma membrane and mitochondria-associated membranes [7,11,12].…”

Section: Introductionmentioning

confidence: 99%

Sigma-1R Agonist Improves Motor Function and Motoneuron Survival in ALS Mice

et al. 2012

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Amyotrophic lateral sclerosis is a neurodegenerative disorder characterized by progressive weakness, muscle atrophy, and paralysis due to the loss of upper and lower motoneurons (MNs). Sigma-1 receptor (sigma-1R) activation promotes neuroprotection after ischemic and traumatic injuries to the central nervous system. We recently reported that sigma-1R agonist (PRE-084) improves the survival of MNs after root avulsion injury in rats. Moreover, a mutation of the sigma-1R leading to frontotemporal lobar degeneration/amyotrophic lateral sclerosis (ALS) was recently described in human patients. In the present study, we analyzed the potential therapeutic effect of the sigma-1R agonist (PRE-084) in the SOD1 G93A mouse model of ALS. Mice were daily administered with PRE-084 (0.25 mg/kg) from 8 to 16 weeks of age. Functional outcome was assessed by electrophysiological tests and computerized analysis of locomotion. Histological, immunohistochemical analyses and Western blot of the spinal cord were performed. PRE-084 administration from 8 weeks of age improved the function of MNs, which was manifested by maintenance of the amplitude of muscle action potentials and locomotor behavior, and preserved neuromuscular connections and MNs in the spinal cord. Moreover, it extended survival in both female and male mice by more than 15 %. Delayed administration of PRE-084 from 12 weeks of age also significantly improved functional outcome and preservation of the MNs. There was an induction of protein kinase C-specific phosphorylation of the NR1 subunit of the N-methyl-D-aspartate (NMDA) receptor in SOD1 G93A animals, and a reduction of the microglial reactivity compared with untreated mice. PRE-084 exerts a dual therapeutic contribution, modulating NMDA Ca 2+ influx to protect MNs, and the microglial reactivity to ameliorate the MN environment. In conclusion, sigma-1R agonists, such as PRE-084, may be promising candidates for a therapeutical strategy of ALS.

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Immunohistochemical localization of the σ1-receptor in oligodendrocytes in the rat central nervous system

Cited by 56 publications

References 35 publications

The cholinergic system, sigma-1 receptors and cognition

The cholinergic system, sigma-1 receptors and cognition

The Lifetime of UDP-galactose:Ceramide Galactosyltransferase Is Controlled by a Distinct Endoplasmic Reticulum-associated Degradation (ERAD) Regulated by Sigma-1 Receptor Chaperones

Sigma-1R Agonist Improves Motor Function and Motoneuron Survival in ALS Mice

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