Effect of DHEA Glutamate Release from Synaptosomes of Rats at Different Ages

Lhullier, Francisco Luiz Rodrigues; Riera, Neusa Gruschinske; Nicolaidis, Rafael; Junqueira, Débora; Dahm, K.; Cipriani, Franciele; Brusque, Ana Maria; Souza, Diogo O.

doi:10.1023/b:nere.0000013735.50736.0a

Cited by 9 publications

(5 citation statements)

References 31 publications

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“…41 However, we also found that extracellular Ca 2þ , but not NMDA receptor or sigma-1 receptor activation, is crucial for presynaptic facilitation of glutamate release by DHEAS. Although our findings were not compatible with those of previous studies, 12,17,40 DHEAS is also known to activate the Ca 2þ -activated K channel (KCa) 42 and Ca 2þ -permeable ion channels, such as P2X purinergic receptors, 5,43 which may account for these discrepancies.…”

Section: Discussioncontrasting

confidence: 99%

“…Our results suggest that DHEAS predominantly enhances nociceptive synaptic transmission at presynaptic sites. Previous studies have shown that DHEAS increased glutamate release from presynaptic terminals 12,40 and potentiated excitatory synaptic transmission 17 via sigma-1 receptor activation. Moreover, presynaptic NMDA receptor activation is thought to be associated with the pathophysiology of neuropathic pain.…”

Section: Discussionmentioning

confidence: 93%

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Neurosteroid dehydroepiandrosterone sulphate enhances pain transmission in rat spinal cord dorsal horn

Yamamoto

Kamiya

Sasaki

et al. 2019

British Journal of Anaesthesia

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Background: The neurosteroid dehydroepiandrosterone sulphate (DHEAS) activates the sigma-1 receptor, inhibits gamma-aminobutyric acid A (GABA A ) and glycine receptors, and induces hyperalgesic effects. Although its effects have been studied in various tissues of the nervous system, its synaptic mechanisms in nociceptive pathways remain to be elucidated. Methods: The threshold of mechanical hypersensitivity and spontaneous pain behaviour was assessed using the von Frey test in adult male Wistar rats after intrathecal administration of DHEAS. We also investigated the effects of DHEAS on synaptic transmission in the spinal dorsal horn using slice patch-clamp electrophysiology. Results: Intrathecally administered DHEAS elicited dose-dependent mechanical hyperalgesia and spontaneous pain behaviours (withdrawal threshold: saline; 51.0 [20.1] g, 3 mg DHEAS; 14.0 [7.8] g, P<0.01, 10 mg DHEAS; 6.9 [5.2] g, 15 min after administration, P<0.001). DHEAS at 100 mM increased the frequency of miniature postsynaptic currents in the rat dorsal spinal horn; this increase was extracellular Ca 2þ -dependent but not sigma-1 and N-methyl-D-aspartate receptordependent. DHEAS suppressed the frequency of miniature inhibitory postsynaptic currents in a GABA A receptor-and sigma-1 receptor-dependent manner. Conclusions: These results suggest that DHEAS participates in the pathophysiology of nociceptive synaptic transmission in the spinal cord by potentiation of glutamate release and inhibition of the GABA A receptor.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 93%

Neurosteroid dehydroepiandrosterone sulphate enhances pain transmission in rat spinal cord dorsal horn

Yamamoto

Kamiya

Sasaki

et al. 2019

British Journal of Anaesthesia

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“…The results obtained are in agreement with previous studies that show a protective effect of DHEA on oxidative stress, apoptosis and alteration in mitochondrial electron transport induced in different experimental models [12,[22][23][24] . In this line, Aragno's group [12] found that DHEA orally at 4 mg/day for 21 days protected against oxidative stress induced by hyperglycemia in rat synaptosomes.…”

Section: Discussionsupporting

confidence: 92%

Treatment with Dehydroepiandrosterone Prevents Oxidative Stress Induced by 3-Nitropropionic Acid in Synaptosomes

Túnez¹,

Muñoz²,

Montilla³

2005

Pharmacology

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This study evaluates the antioxidative effect of dehydroepiandrosterone (DHEA) treatment on 3-nitropropionic acid (3-NPA)-induced oxidative stress in striatal and brain cortex synaptosomes. The oxidative derangement was confirmed by a high level of lipid peroxidation products and protein carbonyls, as well as by an enhanced superoxide dismutase activity (p < 0.001). These changes were partially prevented by DHEA. Moreover, 3-NPA induced a drop in succinate dehydrogenase activity, while DHEA treatment restored the succinate dehydrogenase activity. These results show that DHEA reduces oxidative stress in synaptosomes isolated from the brain of 3-NPA-treated rats, and they suggest this neurosteroid may protect mitochondrial and maintain synaptic integrity against damage induced by this acid.

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“…In the present study, in vivo DHEA administration was tested for its tentative neuroprotection and antioxidative role. Lhullier et al (2004) demonstrated that in vitro effect of DHEA on synaptosomal glutamate release depends on the age of rats, it decreases the basal glutamate release from synaptosomes of old rats (12 months), with no effect on young rats (17 days). DHEA and DHEAS (100 nm) can prevent/reduce the neurotoxicity of NMDA, both in vitro and in vivo models (Kimonides et al 1998).…”

Section: Discussionmentioning

confidence: 98%

Effect of dehydroepiandrosterone (DHEA) on monoamine oxidase activity, lipid peroxidation and lipofuscin accumulation in aging rat brain regions

et al. 2008

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Dehydroepiandrosterone (DHEA), one of the major steroid hormones, and its ester have recently received attention with regard to aging and age-related diseases like Alzheimer and others. DHEA is synthesized de novo in the brain and its substantial fall with age has been shown to be associated with neuronal vulnerability to neurotoxicity processes. Thus, DHEA is considered to be a neuroactive pharmacological substance with potential antiaging properties. A prominent feature that accompanies aging is an increase in monoamine oxidase (MAO). Increased MAO activity with correlated increase in lipid peroxidation in the aging rat brain supports the hypothesis that catecholamine oxidation is an important source of oxidative stress. The progressive accumulation of lipofuscin in neuronal cells is one of the most characteristic age related changes, an increase in body weight was also observed at 24 months. The objective of this study was to observe the changes in monoamine oxidase activity, lipid peroxidation levels and lipofuscin accumulation occurring in aging rat brain regions, and to see whether these changes are restored to normal levels after exogenous administration of DHEA (30 mg/kg/day for 1 month). The results obtained in the present work revealed that normal aging was associated with significant increases in the activity of monoamine oxidase, lipid peroxidation levels and lipofuscin accumulation in brain regions of 4, 14 and 24 months age group male rats. The present study showed that DHEA treatment significantly decreased monoamine oxidase activity, lipid peroxidation and lipofuscin accumulation in brain regions of aging rats, the increased body weight at 24 months also decreased more than the age matched controls. It can therefore be suggested that DHEA's beneficial effects seemed to arise from its antioxidant, antiobesity, antilipofuscin, antilipidperoxidative and thereby anti-aging actions. The results of this study will be useful for pharmacological modification of the aging process and development of new drugs for age related disorders.

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Effect of DHEA Glutamate Release from Synaptosomes of Rats at Different Ages

Cited by 9 publications

References 31 publications

Neurosteroid dehydroepiandrosterone sulphate enhances pain transmission in rat spinal cord dorsal horn

Neurosteroid dehydroepiandrosterone sulphate enhances pain transmission in rat spinal cord dorsal horn

Treatment with Dehydroepiandrosterone Prevents Oxidative Stress Induced by 3-Nitropropionic Acid in Synaptosomes

Effect of dehydroepiandrosterone (DHEA) on monoamine oxidase activity, lipid peroxidation and lipofuscin accumulation in aging rat brain regions

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