Koohestani Faezeh, Brown Chester M, Meisami Esmail
Department of Molecular & Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States.
Int J Dev Neurosci. 2012 Nov;30(7):570-7. doi: 10.1016/j.ijdevneu.2012.07.006. Epub 2012 Aug 14.
The plasticity and vulnerability of the rat spinal cord (SC) during postnatal development has been less investigated compared to other CNS structures. In this study, we determined the effects of thyroid hormonal (TH) deficiency and excess on postnatal growth and neurochemical development of the rat SC. The growth as well as the specific and total activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes of the SC were determined in hypo- and hyperthyroid rat pups at postnatal (P) days P1, P5, P10 and P21 (weaning), and were compared to age-matched untreated normal controls. AChE is a cholinergic synaptic enzyme while BuChE is a metabolic enzyme mainly found in glial cells and neurovascular cells. The SC is rich in somatic motor, autonomic cholinergic neurons and associated interneurons. Daily subcutaneous injection of pups with thyroxine (T4) and administration of antithyroid goitrogen propylthiouracil (PTU) in the litter's drinking water were used to induce hyper- and hypothyroidism, respectively. Enzyme assays were carried out spectrophotometrically at the above-mentioned ages, using SC homogenates with acetylthiocholine-chloride as the substrate, together with specific cholinesterase inhibitors, which specifically target AChE and BuChE. SC weights were significantly lower at P10 and P21 in hypothyroid pups but unchanged in the hyperthyroid ones. Hypothyroidism significantly reduced both specific and total AChE activity in SC of P10 and P21 rat pups, while having no effects on the BuChE activity, although total BuChE activity was decreased due to reduced total tissue weight. In contrast both specific and total AChE activities were markedly and significantly increased (>100%) in the P10 and P21 hyperthyroid pups. However, BuChE specific activity was unaffected by this treatment. The results indicate that hypothyroid condition significantly reduces, while hyperthyroidism increases, the postnatal development of cholinergic synapses, thereby influencing the functional development of this major sensory and motor structure. However, the neurochemical development of glia and other non-neuronal cells, where BuChE is mainly localized, is comparatively unaffected in these abnormal developmental conditions.
与其他中枢神经系统结构相比，出生后发育期间大鼠脊髓（SC）的可塑性和脆弱性研究较少。在本研究中，我们确定了甲状腺激素（TH）缺乏和过量对大鼠脊髓出生后生长和神经化学发育的影响。在出生后（P）第1、5、10和21天（断奶）的甲状腺功能减退和甲状腺功能亢进的幼鼠中，测定了脊髓中乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BuChE）的生长以及特异性和总活性，并与年龄匹配的未处理正常对照进行比较。AChE是一种胆碱能突触酶，而BuChE是一种主要存在于神经胶质细胞和神经血管细胞中的代谢酶。脊髓富含躯体运动、自主胆碱能神经元和相关的中间神经元。分别通过每天给幼鼠皮下注射甲状腺素（T4）以及在幼鼠饮用水中添加抗甲状腺促甲状腺肿物质丙硫氧嘧啶（PTU）来诱导甲状腺功能亢进和减退。在上述年龄使用分光光度法进行酶活性测定，使用以氯化乙酰硫代胆碱为底物的脊髓匀浆以及特异性靶向AChE和BuChE的特异性胆碱酯酶抑制剂。甲状腺功能减退的幼鼠在P10和P21时脊髓重量显著降低，但甲状腺功能亢进的幼鼠脊髓重量无变化。甲状腺功能减退显著降低了P10和P21大鼠幼鼠脊髓中AChE的特异性和总活性，而对BuChE活性无影响，尽管由于总组织重量降低，总BuChE活性有所下降。相反，在P10和P21的甲状腺功能亢进幼鼠中，AChE的特异性和总活性均显著增加（>100%）。然而，这种处理对BuChE的特异性活性没有影响。结果表明，甲状腺功能减退显著降低，而甲状腺功能亢进增加了胆碱能突触的出生后发育，从而影响了这个主要感觉和运动结构的功能发育。然而，在这些异常发育条件下，主要定位于神经胶质细胞和其他非神经元细胞中的BuChE的神经化学发育相对未受影响。
