Resveratrol Regulates N-Methyl-D-Aspartate Receptor Expression and Suppresses Neuroinflammation in Morphine-Tolerant Rats

Tsai, Ray Jui-Fang; Chou, Kuang-Yi; Shen, Ching-Hui; Chien, Chih Cheng; Tsai, Wei-Yuan; Huang, Yu‐ming M.; Tao, Pao‐Luh; Lin, Yu‐Ju; Wong, Chih‐Shung

doi:10.1213/ane.0b013e31825da0fb

Cited by 39 publications

(26 citation statements)

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“…Knowing that resveratrol has an anti-nociceptive effect in some pain models [20], [21], [22], [23] and works as an activator of SIRT1 as reported in the literature [37], [38], we further asked whether resveratrol could delay the development of neuropathic pain. It was found in our study that an intrathecal administration of 5 µl 90 mM resveratrol [21], [30], [31] 1 h before CCI surgery, but not 45 mM, delayed the onset of thermal hyperalgesia (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…In addition, SIRT1 is a major effector of axonal protection mediated by increased NAD biosynthesis [18]. Resveratrol (3,4′,5-trihydroxystilbene), a phytoalexin naturally present in plants, binds to SIRT1 at the N-terminal and then increases SIRT1 activity [19], showing promising potential for the treatment of pain mediated by nucleus pulposus [20] and the attenuation of neuropathic pain [21], [22] and inflammatory pain [23]. EX-527 (6-chloro-2, 3, 4, 9-tetrahydro-1-H-carbazole-1-carboxamide), a SIRT1 inhibitor that is more potent and selective than other current SIRT1 inhibitors [24], can induce p53 acetylation and cell death through targeting SIRT1 [25].…”

Section: Introductionmentioning

confidence: 99%

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Spinal SIRT1 Activation Attenuates Neuropathic Pain in Mice

et al. 2014

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Abnormal histone acetylation occurs during neuropathic pain through an epigenetic mechanism. Silent information regulator 1 (sir2 or SIRT1), a NAD-dependent deacetylase, plays complex systemic roles in a variety of processes through deacetylating acetylated histone and other specific substrates. But the role of SIRT1 in neuropathic pain is not well established yet. The present study was intended to detect SIRT1 content and activity, nicotinamide (NAM) and nicotinamide adenine dinucleotide (NAD) in the spinal cord using immunoblotting or mass spectroscopy over time in mice following chronic constriction injury (CCI) or sham surgery. In addition, the effect of intrathecal injection of NAD or resveratrol on thermal hyperalgesia and mechanical allodynia was evaluated in CCI mice. Finally, we investigated whether SIRT1 inhibitor EX-527 could reverse the anti-nociceptive effect of NAD or resveratrol. It was found that spinal SIRT1 expression, deacetylase activity and NAD/NAM decreased significantly 1, 3, 7, 14 and 21 days after CCI surgery as compared with sham group. In addition, daily intrathecal injection of 5 µl 800 mM NAD 1 h before and 1 day after CCI surgery or single intrathecal injection of 5 µl 90 mM resveratrol 1 h before CCI surgery produced a transient inhibitory effect on thermal hyperalgesia and mechanical allodynia in CCI mice. Finally, an intrathecal injection of 5 µl 1.2 mM EX-527 1 h before NAD or resveratrol administration reversed the anti-nociceptive effect of NAD or resveratrol. These data indicate that the reduction in SIRT1 deacetylase activity may be a factor contributing to the development of neuropathic pain in CCI mice. Our findings suggest that the enhancement of spinal NAD/NAM and/or SIRT1 activity may be a potentially promising strategy for the prevention or treatment of neuropathic pain.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Spinal SIRT1 Activation Attenuates Neuropathic Pain in Mice

et al. 2014

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“…In accordance, morphine promotes phosphorylation of NMDAR subunits and greater expression of GluN2B containing NMDARs at the membrane [19; 25; 28; 73; 90]. MOR and NMDAR interactions at the neuronal membrane would be key in these morphine-induced changes [19].…”

Section: Discussionmentioning

confidence: 99%

GluN2B N-methyl-D-aspartate receptor and excitatory amino acid transporter 3 are upregulated in primary sensory neurons after 7 days of morphine administration in rats

Gong

Bhargava

Jasmin

2016

Pain

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The contribution of the peripheral nervous system to opiate-induced hyperalgesia (OIH) is not well understood. Here, we determined the changes in excitability of primary sensory neurons after sustained morphine administration for 7 days. Changes in expression of glutamate receptors and glutamate transporters after morphine administration were ascertained in dorsal root ganglions (DRGs). Patch clamp recordings from intact DRGs (ex-vivo preparation) of morphine-treated rats showed increased excitability of small diameter (≤ 30 μm) neurons with respect to rheobase and membrane threshold, whereas the excitability of large diameter (> 30 μm) neurons remained unchanged. Small diameter neurons also displayed increased responses to glutamate, which were mediated mainly by GluN2B containing NMDA receptors (NMDARs), and to a lesser degree by the neuronal excitatory amino acid transporter 3 /excitatory amino acid carrier 1 (EAAT3/EAAC1). Co-administration in vivo of the GluN2B selective antagonist Ro 25-6981 with morphine for 7 days prevented the appearance of OIH and increased morphine-induced analgesia. Administration of morphine for 7 days led to an increased expression of GluN2B and EAAT3/EAAC1, but not of the AMPA, kainate or Group I metabotropic glutamate receptors, or of the vesicular glutamate transporter 2 (VGLUT2). These results suggest that peripheral glutamatergic neurotransmission contributes to OIH and that GluN2B subunit of NMDARs in the periphery may be a target for therapy.

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“…Resveratrol memiliki fungsi dalam memperbaiki keadaan eksitotosisitas. 35 Adanya fungsi perbaikan ini menunjukkan hubungan yang kuat pada penurunan jumlah neuron yang rusak yang akan menyebabkan penurunan volume infark.…”

Section: Pembahasanunclassified

Ekstrak Kulit dan Biji Anggur (Vitis vinifera) Menurunkan Jumlah Sel Neuron yang Rusak, Volume Infark, dan Memperbaiki Fungsi Motorik pada Tikus Wistar Model Stroke Iskemik

Lukito¹,

Indra²

2016

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ABSTRAKStroke iskemik merupakan penyakit karena tersumbatnya pembuluh darah ke otak sehingga menyebabkan kerusakan neurologis. Kerusakan ini akibat perubahan seluler yang menyebabkan kerusakan neuron, edema otak, dan penurunan fungsi motorik. Ekstrak kulit dan biji anggur (Vitis vinifera) mengandung resveratrol yang mampu melintasi sawar darah otak dan memperbaiki kematian neuron melalui jalur patofisiologi seluler serta menginduksi ERK 1/2 pathway untuk regenerasi otak. Pada penelitian ini ingin diketahui korelasi antara perbaikan jumlah neuron yang rusak, volume infark, dan fungsi motorik setelah pemberian ekstrak kulit dan biji anggur pada tikus. Penelitian eksperimental ini menggunakan tikus (Rattus norvegicus) yang terbagi menjadi 5 kelompok yaitu (1) kontrol positif (+), (2) kontrol negatif (-), (3) dosis ekstrak 50 mg/kgBB, (4) dosis ekstrak 100 mg/kgBB, dan (5) dosis ekstrak 200 mg/kgBB. Ekstrak diberikan selama 2 minggu. Tikus diinduksi stroke dengan metode unilateral carotid artery occlusion selama 45 menit. Kemudian diuji fungsi motoriknya dengan ladder rung walking test. Setelah 2 minggu, dianalisis fungsi motorik, jumlah neuron yang rusak dan volume infark dengan metode hematoksilin & eosin. Berdasarkan uji Pearson terdapat korelasi yang cukup antara fungsi motorik dengan jumlah neuron yang rusak maupun volume infark (berturut-turut R = 0,306; R = 0,346). Sementara antara jumlah neuron yang rusak dengan volume infark terdapat korelasi yang kuat (R = 0,645, p = 0,002; p  0,05). Kesimpulannya terdapat korelasi antara perbaikan jumlah sel neuron yang rusak, volume infark, dan fungsi motorik.Kata kunci: Kulit dan biji anggur, Motorik, Infark, Regenerasi otak, Resveratrol, Stroke. Grape (Vitis vinifera) Peel and Seed Extract Decrease the Damaged Neurons, Infarc Volume, and Repair Motoric Function in Ischemic Stroke Rat Model ABSTRACTIschemic stroke is a disease that caused by blockage of blood circulation in brain, then resulting in neurological failure. This is due to cellular changes that lead to damaged neurons, brain edema, and motoric function impairment. Grape (Vitis vinifera) peel and seed extract contain resveratrol which is able to pass through blood brain barrier and improve neuron death through cellular pathway and induce ERK 1/2 pathway for brain regeneration. This study aim is to find the correlation between damaged neurons, infarct volume, and motoric function improvement after grape peel and seed extract treatment in rats. This experimental study used rats that were divided into 5 groups, (1) positive control, (2) negative control, (3) extract concentration 50 mg/kgBB, (4) extract concentration100mg/kgBW, and (5) extract concentration 200mg/kgBW. They were treated with grape peel and seed extract in 2 weeks. Inducing stroke performed with unilateral carotid artery occlusion for 45 minutes. Motoric function was assessed by ladder rung walking test. After 2 weeks, motoric function reassessment, damaged neurons and infarct volume were evaluated by hematoxylin & eosin staining. Based on Pears...

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Resveratrol Regulates N-Methyl-D-Aspartate Receptor Expression and Suppresses Neuroinflammation in Morphine-Tolerant Rats

Abstract: Resveratrol attenuates morphine tolerance by inhibiting neuroinflammation and down-regulating NMDAR NR1 and NR2B subunit expression. Resveratrol regulates the NMDAR expression, which might be involved in a loss of scaffolding postsynaptic density-95 protein.

Cited by 39 publications

References 50 publications

Spinal SIRT1 Activation Attenuates Neuropathic Pain in Mice

Spinal SIRT1 Activation Attenuates Neuropathic Pain in Mice

GluN2B N-methyl-D-aspartate receptor and excitatory amino acid transporter 3 are upregulated in primary sensory neurons after 7 days of morphine administration in rats

Ekstrak Kulit dan Biji Anggur (Vitis vinifera) Menurunkan Jumlah Sel Neuron yang Rusak, Volume Infark, dan Memperbaiki Fungsi Motorik pada Tikus Wistar Model Stroke Iskemik

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