Neurosteroid dehydroepiandrosterone sulfate enhances spontaneous glutamate release in rat prelimbic cortex through activation of dopamine D1 and sigma-1 receptor

Dong, Lian-Yan; Cheng, Zhengxiang; Fu, Yingmei; Wang, Zemin; Zhu, Yanhua; Sun, Jianli; Dong, Yi; Zheng, Ping

doi:10.1016/j.neuropharm.2006.10.015

Cited by 64 publications

(37 citation statements)

References 45 publications

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“…DHEA-S, another neurosteroid with sigma-1 receptor agonist action, also enhances the spontaneous release of glutamate in prelimbic cortex and hippocampus. The effect of this compound in the prelimbic cortex appears to be mediated via dopamine D 1 and sigma-1 receptors, whereas that in the hippocampus occurs only via sigma-1 receptors [23].…”

Section: Modulation Of Glutamate Release By Sigma-1 Agonistsmentioning

confidence: 96%

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: Modulation Of Glutamate Release By Sigma-1 Agonistsmentioning

confidence: 96%

The cholinergic system, sigma-1 receptors and cognition

Waarde

Ramakrishnan

Rybczynska

et al. 2011

Behavioural Brain Research

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“…37 These inhibitors, however, have a low efficacy (IC 50 40.4 and 3 mmol/L, respectively) and limited solubility in ACSF, factors that made the use of 6-aminonicotinamide impossible in our experiments. Conversely, dehydroepiandrosterone at 0.3 mmol/L concentration induced strong hyperexcitability manifested by drastic increase in field responses and emergence of interictal spontaneous activity (Supplementary Figure S2), effects that may be explained by its multi-faceted and unspecific activity (e.g., inhibition of GABA A receptors 38 or increase in spontaneous glutamate release 39 ). To verify the role of ROS in MC induction we superfused slices with pyruvate-ACSF containing IOA as well as an efficient antioxidant, Tempol (2 mmol/L).…”

Section: Replacement Of Glucose With Mitochondrial Energy Substrates mentioning

confidence: 99%

Reactive Oxygen Species Initiate a Metabolic Collapse in Hippocampal Slices: Potential Trigger of Cortical Spreading Depression

Malkov

Ivanov

Popova

et al. 2014

J Cereb Blood Flow Metab

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Excessive accumulation of reactive oxygen species (ROS) underlies oxidative damage. We find that in hippocampal slices, decreased activity of glucose-based antioxidant system induces a massive, abrupt, and detrimental change in cellular functions. We call this phenomenon metabolic collapse (MC). This collapse manifested in long-lasting silencing of synaptic transmission, abnormal oxidation of NAD(P)H and FADH 2 associated with immense oxygen consumption, and massive neuronal depolarization. MC occurred without any preceding deficiency in neuronal energy supply or disturbances of ionic homeostasis and spread throughout the hippocampus. It was associated with a preceding accumulation of ROS and was largely prevented by application of an efficient antioxidant Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl). The consequences of MC resemble cortical spreading depression (CSD), a wave of neuronal depolarization that occurs in migraine, brain trauma, and stroke, the cellular initiation mechanisms of which are poorly understood. We suggest that ROS accumulation might also be the primary trigger of CSD. Indeed, we found that Tempol strongly reduced occurrence of CSD in vivo, suggesting that ROS accumulation may be a key mechanism of CSD initiation.

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“…In our previous study, we reported that DHEAS at concentrations Ն15 M could increase spontaneous glutamate release in the prelimbic cortex (Dong et al, 2007). Here, we reported that at a lower concentration (1 M), DHEAS could significantly inhibit the 5-HT-evoked glutamate release in this brain region.…”

Section: Discussionmentioning

confidence: 49%

“…However, when the concentration of DHEAS was at a higher range, its effect decreased with the increase in concentration. This decrease may be related to the fact that when DHEAS is at higher concentrations, it can promote spontaneous glutamate release (Dong et al, 2007), which may counter the inhibitory effect of DHEAS.…”

Section: Discussionmentioning

confidence: 99%

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Neuroactive Steroid Dehydroepiandrosterone Sulfate Inhibits 5-Hydroxytryptamine (5-HT)-Evoked Glutamate Release via Activation of σ-1 Receptors and Then Inhibition of 5-HT₃Receptors in Rat Prelimbic Cortex

Dong

Zhu²,

Dong³

et al. 2009

J Pharmacol Exp Ther

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Dehydroepiandrosterone sulfate (DHEAS) is one of the most important neuroactive steroids. The present study examined the effect of DHEAS on spontaneous and evoked glutamate release in the pyramidal cells of layers V and VI of the rat prelimbic cortex by using whole-cell patch-clamp recordings in slices and further investigated its mechanism. The results showed that DHEAS at 1 M had no effect on spontaneous glutamate release but inhibited 5-hydroxytryptaime (5-HT)-evoked glutamate release. The concentration-response relationship of this effect of DHEAS was U-shaped with a maximum at 1 M, and this inhibition seemed to have some extent of selectivity for the 5-HT-evoked glutamate release because it had no effects on high K ϩ -, electrical stimulus-, and dopamineevoked releases. Further study showed that DHEAS inhibited the 5-HT 3 receptor agonist evoked-glutamate release but had no effect on the 5-HT 2A/2C receptor agonist-evoked release. Moreover, the 5-HT 3 receptor antagonist could block the effect of DHEAS on the 5-HT-evoked glutamate release. The mechanism study showed that the -1 receptor antagonist could block the effect of DHEAS and that the -1 receptor agonist could mimic the effect of DHEAS on 5-HT 3 receptor agonistevoked glutamate release and intrasynaptosomal Ca 2ϩ increase. These results suggest that DHEAS can inhibit 5-HTevoked glutamate release via activation of the -1 receptor and then inhibition of the 5-HT 3 receptor in the pyramidal cells of the prelimbic cortex.

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Neurosteroid dehydroepiandrosterone sulfate enhances spontaneous glutamate release in rat prelimbic cortex through activation of dopamine D1 and sigma-1 receptor

Cited by 64 publications

References 45 publications

The cholinergic system, sigma-1 receptors and cognition

The cholinergic system, sigma-1 receptors and cognition

Reactive Oxygen Species Initiate a Metabolic Collapse in Hippocampal Slices: Potential Trigger of Cortical Spreading Depression

Neuroactive Steroid Dehydroepiandrosterone Sulfate Inhibits 5-Hydroxytryptamine (5-HT)-Evoked Glutamate Release via Activation of σ-1 Receptors and Then Inhibition of 5-HT₃Receptors in Rat Prelimbic Cortex

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Neurosteroid dehydroepiandrosterone sulfate enhances spontaneous glutamate release in rat prelimbic cortex through activation of dopamine D1 and sigma-1 receptor

Cited by 64 publications

References 45 publications

The cholinergic system, sigma-1 receptors and cognition

The cholinergic system, sigma-1 receptors and cognition

Reactive Oxygen Species Initiate a Metabolic Collapse in Hippocampal Slices: Potential Trigger of Cortical Spreading Depression

Neuroactive Steroid Dehydroepiandrosterone Sulfate Inhibits 5-Hydroxytryptamine (5-HT)-Evoked Glutamate Release via Activation of σ-1 Receptors and Then Inhibition of 5-HT3Receptors in Rat Prelimbic Cortex

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Neuroactive Steroid Dehydroepiandrosterone Sulfate Inhibits 5-Hydroxytryptamine (5-HT)-Evoked Glutamate Release via Activation of σ-1 Receptors and Then Inhibition of 5-HT₃Receptors in Rat Prelimbic Cortex