Agriculture and Life Sciences Faculty, Lincoln University, Lincoln 7647, New Zealand.
Neurochem Int. 2009 Dec;55(8):783-8. doi: 10.1016/j.neuint.2009.07.012. Epub 2009 Aug 5.
Anomalies in neuropeptides and neuroactive amino acids have been postulated to play a role in neurodegeneration in a variety of diseases including the inherited neuronal ceroid lipofuscinoses (NCLs, Batten disease). These are often indicated by concentration changes in cerebrospinal fluid (CSF). Here we compare CSF neuropeptide concentrations in patients with the classical juvenile CLN3 form of NCL and the classical late infantile CLN2 form with neuropeptide and neuroactive amino acid concentrations in CSF from sheep with the late infantile variant CLN6 form. A marked disease related increase in CSF concentrations of neuron specific enolase and tau protein was noted in the juvenile CLN3 patients but this was not observed in an advanced CLN2 patient nor CLN6 affected sheep. No changes were noted in S-100b, GFAP or MBP in patients or of S-100b, GFAP or IGF-1 in affected sheep. There were no disease related changes in CSF concentrations of the neuroactive amino acids, aspartate, glutamate, serine, glutamine, glycine, taurine and GABA in these sheep. The changes observed in the CLN3 patients may be progressive markers of neurodegeneration, or of underlying metabolic changes perhaps associated with CLN3 specific changes in neuroactive amino acids, as have been postulated. The lack of changes in the CLN2 and CLN6 subjects indicate that these changes are not shared by the CLN2 or CLN6 forms and changes in CSF concentrations of these compounds are unreliable as biomarkers of neurodegeneration in the NCLs in general.
神经肽和神经活性氨基酸的异常被认为在多种疾病的神经退行性变中起作用，包括遗传性神经元蜡样脂褐质沉积症（NCLs，Batten 病）。这些通常表现为脑脊液（CSF）中浓度的变化。在这里，我们比较了经典少年型 CLN3 型 NCL 和经典晚婴型 CLN2 型患者的 CSF 神经肽浓度，以及晚婴型 CLN6 变异型 CLN6 型羊的 CSF 中神经肽和神经活性氨基酸浓度。在少年型 CLN3 患者中，CSF 中神经元特异性烯醇酶和 tau 蛋白的浓度明显升高，但在晚期 CLN2 患者和 CLN6 型羊中未观察到这种情况。在患者中，S-100b、GFAP 或 MBP 或在受影响的羊中，S-100b、GFAP 或 IGF-1 均未发生变化。在这些羊中，神经活性氨基酸天冬氨酸、谷氨酸、丝氨酸、谷氨酰胺、甘氨酸、牛磺酸和 GABA 的 CSF 浓度均未发生与疾病相关的变化。在 CLN3 患者中观察到的变化可能是神经退行性变的进行性标志物，或者是潜在的代谢变化，可能与神经活性氨基酸的 CLN3 特异性变化有关，正如推测的那样。CLN2 和 CLN6 受试者中没有变化表明这些变化不是 CLN2 或 CLN6 形式所共有的，并且这些化合物 CSF 浓度的变化作为 NCL 神经退行性变的生物标志物不可靠。
