The role of the neuropeptide somatostatin on methamphetamine and glutamate-induced neurotoxicity in the striatum of mice.
The role of the neuropeptide somatostatin on methamphetamine and glutamate-induced neurotoxicity in the striatum of mice.
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DOI：
10.1016/j.brainres.2013.03.010
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发表时间：
2013-05-13
期刊：
影响因子：
2.9
通讯作者：
Angulo JA
中科院分区：
文献类型：
--
作者：
Afanador L;Mexhitaj I;Diaz C;Ordonez D;Baker L;Angulo JA
大量证据表明，甲基苯丙胺（METH）对动物模型和人类METH使用者的大脑造成持续损害。在长期使用者中，有认知和运动缺陷的迹象。纹状体神经肽能够调节METH的神经化学作用，从而调节纹状体神经损伤。生长抑素（SST）是一种内在的纹状体神经肽，已被证明可抑制谷氨酸传递;谷氨酸是甲基毒性的组成部分，并有助于一氧化氮（NO）的合成。我们假设SST将通过抑制NO合成从而减少氧化应激来保护METH。为此，在全身注射METH（30 mg/kg）之前，将SST类似物奥曲肽（OCT）微量注射到纹状体中。然后，我们评估了3-硝基酪氨酸（3-NT）（NO产生的间接指标）、酪氨酸羟化酶（TH）蛋白水平（多巴胺末端标记物）和Fluoro-Jade C阳性细胞（退化细胞）。SST激动剂OCT剂量依赖性地减弱了MET诱导的纹状体3-NT的积累。此外，OCT预处理有效地减轻了细胞死亡，但未能保护多巴胺末梢。接下来，我们共输注OCT和NMDA并测量3-NT和Fluoro-Jade C染色。OCT治疗对这些参数无影响。这些数据表明，SST减弱了MET诱导的NO产生，保护纹状体免受MET诱导的细胞损失。然而，SST未能阻止多巴胺末梢的毒性，这表明突触前和突触后纹状体损伤通过独立的机制发生。
A large body of evidence shows that methamphetamine (METH) causes sustained damage to the brain in animal models and human METH users. In chronic users there are indications of cognitive and motor deficits. Striatal neuropeptides are in a position to modulate the neurochemical effects of METH and consequently striatal neural damage. Somatostatin (SST) is an intrinsic striatal neuropeptide that has been shown to inhibit glutamate transmission; glutamate is integral to METH toxicity and contributes to nitric oxide (NO) synthesis. We hypothesize that SST will protect from METH by inhibition of NO synthesis and thus reducing oxidative stress. To this end, the SST analogue octreotide (OCT) was microinjected into the striatum prior to a systemic injection of METH (30 mg/kg). We then assessed 3-nitrotyrosine (3-NT), an indirect index of NO production, tyrosine hydroxylase (TH) protein levels (dopamine terminal marker) and Fluoro-Jade C positive cells (degenerating cells). The SST agonist OCT dose dependently attenuated the METH-induced accumulation of striatal 3-NT. Moreover, pretreatment with OCT effectively mitigated cell death but failed to protect dopamine terminals. Next we co-infused OCT and NMDA and measured 3-NT and Fluoro-Jade C staining. Treatment with OCT had no effect on these parameters. The data demonstrate that SST attenuates the METH-induced production of NO protecting the striatum from the METH-induced cell loss. However, SST failed to prevent the toxicity of the dopamine terminals suggesting that pre- and post-synaptic striatal damage occur via independent mechanisms.
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DOI：
10.1016/s0169-328x(01)00184-x
发表时间：
2001-09-10
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Deng, XL;Wang, Y;Cadet, JL
通讯作者：
Cadet, JL
影响因子：
4.8
作者：
Cordelier, Pierre;Esteve, Jean-Pierre;Buscail, Louis
通讯作者：
Buscail, Louis
影响因子：
5
作者：
FIBIGER, HC;MCGEER, EG
通讯作者：
MCGEER, EG
影响因子：
1.8
作者：
Desaiah, D;Reddy, SLN;Ali, SF
通讯作者：
Ali, SF
影响因子：
--
作者：
Arena, S;Pattarozzi, A;Florio, T
通讯作者：
Florio, T