Bagga Puneet, Chugani Anup N, Patel Anant B
CSIR-Centre for Cellular and Molecular Biology, Habsiguda, Uppal Road, Hyderabad, 500007, India.
CSIR-Centre for Cellular and Molecular Biology, Habsiguda, Uppal Road, Hyderabad, 500007, India.
Neurochem Int. 2016 Jan;92:25-34. doi: 10.1016/j.neuint.2015.11.006. Epub 2015 Dec 2.
Parkinson's disease (PD) is a neurodegenerative disorder characterized by degeneration of nigrostriatal dopaminergic neurons with an accompanying neuroinflammation leading to loss of dopamine in the basal ganglia. Caffeine, a well-known A2A receptor antagonist is reported to slow down the neuroinflammation caused by activated microglia and reduce the extracellular glutamate in the brain. In this study, we have evaluated the neuroprotective effect of caffeine in the MPTP model of PD by monitoring the region specific cerebral energy metabolism. Adult C57BL6 mice were treated with caffeine (30 mg/kg, i.p.) 30 min prior to MPTP (25 mg/kg, i.p.) administration for 8 days. The paw grip strength of mice was assessed in order to evaluate the motor function after various treatments. For metabolic studies, mice were infused with [1,6-(13)C2]glucose, and (13)C labeling of amino acids was monitored using ex vivo(1)H-[(13)C]-NMR spectroscopy. The paw grip strength was found to be reduced following the MPTP treatment. The caffeine pretreatment showed significant protection against the reduction of paw grip strength in MPTP treated mice. The levels of GABA and myo-inositol were found to be elevated in the striatum of MPTP treated mice. The (13)C labeling of GluC4, GABAC2 and GlnC4 from [1,6-(13)C2]glucose was decreased in the cerebral cortex, striatum, olfactory bulb, thalamus and cerebellum suggesting impaired glutamatergic and GABAergic neuronal activity and neurotransmission of the MPTP treated mice. Most interestingly, the pretreatment of caffeine maintained the (13)C labeling of amino acids to the control values in cortical, olfactory bulb and cerebellum regions while it partially retained in striatal and thalamic regions in MPTP treated mice. The pretreatment of caffeine provides a partial neuro-protection against severe striatal degeneration in the MPTP model of PD.
帕金森病（PD）是一种神经退行性疾病，其特征是黑质纹状体多巴胺能神经元变性，并伴有神经炎症，导致基底神经节中多巴胺丧失。咖啡因是一种著名的A2A受体拮抗剂，据报道它能减缓由活化小胶质细胞引起的神经炎症，并减少大脑中的细胞外谷氨酸。在本研究中，我们通过监测区域特异性脑能量代谢，评估了咖啡因在帕金森病MPTP模型中的神经保护作用。成年C57BL6小鼠在腹腔注射MPTP（25mg/kg）前30分钟腹腔注射咖啡因（30mg/kg），持续8天。为了评估各种处理后的运动功能，对小鼠的爪握力进行了评估。对于代谢研究，给小鼠注入[1,６-(13)C2]葡萄糖，并使用离体1H-[(13)C]-NMR光谱监测氨基酸的(13)C标记。发现MPTP处理后爪握力降低。咖啡因预处理对MPTP处理小鼠爪握力的降低显示出显著的保护作用。发现MPTP处理小鼠纹状体中GABA和肌醇水平升高。来自[1,６-(13)C2]葡萄糖的GluC4、GABAC2和GlnC4的(13)C标记在大脑皮层、纹状体、嗅球、丘脑和小脑中降低，表明MPTP处理小鼠的谷氨酸能和GABA能神经元活动及神经传递受损。最有趣的是，咖啡因预处理使皮质、嗅球和小脑区域的氨基酸(13)C标记维持在对照值，而在MPTP处理的小鼠中，纹状体和丘脑区域则部分保留。咖啡因预处理对帕金森病MPTP模型中严重的纹状体变性提供了部分神经保护作用。
