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成年雄性大鼠癫痫持续状态后海马和内嗅皮质中糖原磷酸化酶的急性和慢性变化

Acute and chronic changes in glycogen phosphorylase in hippocampus and entorhinal cortex after status epilepticus in the adult male rat.

作者信息

Walling Susan G, Rigoulot Marie-Aude, Scharfman Helen E

机构信息

Center for Neural Recovery and Rehabilitation Research, Helen Hayes Hospital, West Haverstraw, New York 10993-1195, USA.

出版信息

Eur J Neurosci. 2007 Jul;26(1):178-89. doi: 10.1111/j.1460-9568.2007.05657.x.

Abstract

Glial cells provide energy substrates to neurons, in part from glycogen metabolism, which is influenced by glycogen phosphorylase (GP). To gain insight into the potential subfield and laminar-specific expression of GP, histochemistry can be used to evaluate active GP (GPa) or totalGP (GPa + GPb). Using this approach, we tested the hypothesis that changes in GP would occur under pathological conditions that are associated with increased energy demand, i.e. severe seizures (status epilepticus or 'status'). We also hypothesized that GP histochemistry would provide insight into changes in the days and weeks after status, particularly in the hippocampus and entorhinal cortex, where there are robust changes in structure and function. One hour after the onset of pilocarpine-induced status, GPa staining was reduced in most regions of the hippocampus and entorhinal cortex relative to saline-injected controls. One week after status, there was increased GPa and totalGP, especially in the inner molecular layer, where synaptic reorganization of granule cell mossy fibre axons occurs (mossy fibre sprouting). In addition, patches of dense GP reactivity were evident in many areas. One month after status, levels of GPa and totalGP remained elevated in some areas, suggesting an ongoing role of GP or other aspects of glycogen metabolism, possibly due to the evolution of intermittent, recurrent seizures at approximately 3-4 weeks after status. Taken together, the results suggest that GP is dynamically regulated during and after status in the adult rat, and may have an important role in the pilocarpine model of epilepsy.

摘要

神经胶质细胞为神经元提供能量底物,部分来源于糖原代谢,而糖原代谢受糖原磷酸化酶(GP)影响。为深入了解GP在潜在亚区域和层特异性的表达情况,可利用组织化学方法评估活性GP(GPa)或总GP(GPa + GPb)。采用这种方法,我们检验了以下假设:在与能量需求增加相关的病理条件下,即严重癫痫发作(癫痫持续状态或“状态”)时,GP会发生变化。我们还假设,GP组织化学将有助于深入了解癫痫持续状态后数天和数周内的变化情况,特别是在海马体和内嗅皮质,这两个区域的结构和功能会发生显著变化。在毛果芸香碱诱导的癫痫持续状态发作1小时后,相对于注射生理盐水的对照组,海马体和内嗅皮质的大多数区域GPa染色减少。癫痫持续状态1周后,GPa和总GP增加,尤其是在颗粒细胞苔藓纤维轴突发生突触重组的内分子层(苔藓纤维出芽)。此外,在许多区域可见密集的GP反应性斑块。癫痫持续状态1个月后,某些区域的GPa和总GP水平仍保持升高,这表明GP或糖原代谢的其他方面持续发挥作用,可能是由于癫痫持续状态后约3 - 4周间歇性、复发性癫痫发作的演变。综上所述,结果表明成年大鼠在癫痫持续状态期间及之后,GP受到动态调节,并且可能在毛果芸香碱癫痫模型中发挥重要作用。

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