D'Intino Giulia, Vaccari Francesca, Sivilia Sandra, Scagliarini Alessandra, Gandini Gualtiero, Giardino Luciana, Calzà Laura
Department of Veterinary Morphophysiology and Animal Production, DIMORFIPA, University of Bologna, Via Tolara di Sopra 50, 40064 Ozzano Emilia, Bologna, Italy.
Brain Res. 2006 Jul 7;1098(1):186-95. doi: 10.1016/j.brainres.2006.04.051. Epub 2006 Jun 9.
In this study, we have investigated the expression of the nuclear transcription factor (c-Fos, NFkB), growth factors (nerve growth factor--NGF, brain-derived neurotrophic factor--BDNF), peptides (enkephalin, galanin) and glutamate transporter (AA 504-523 rat EAAC1) in 6 dogs sacrificed immediately after seizure attack during encephalomyelitis due to canine distemper virus (CDV) (as assessed by clinical examination, RT-PCR and viral RNA detection either in blood or brain tissue and CDV immunohistochemistry in brain slices). In all these CDV affected dogs, the observed neurological signs included untreatable seizures, leading to cluster seizure activity and status epilepticus. In the inter-ictal phase abnormal mentation, postural and gait deficits and sometimes involuntary movements such as myoclonus were recorded. The same investigation was carried out in 5 control dogs affected by different disorders, all characterized by the absence of seizures. Brains were dissected out immediately after euthanasia and fixed; sections collected from the dorsal hippocampus were processed for immunohistochemistry. By comparing hippocampus sections obtained from dog with and without seizure, the following regulations were observed. A strong up-regulation of glutamate transporter throughout the cell layers was found together with the onset of nuclear Fos and NFkB-IR in the pyramidal cell layer X. Among the investigated peptides, we observed a slight increase in enkephalinergic fibers and a strong up-regulation of mu-opioid receptors, whereas galanin-IR seemed to be weaker. Finally, both NGF and BDNF expression was strongly up-regulated. BDNF-IR was mainly localized in the apical dendrite in pyramidal neurons. To our knowledge, these data offer the first indication that molecular events described in experimental kindling also occur during spontaneous pathology in animal species sharing close similarities to human neuropathology.
在本研究中，我们调查了6只因犬瘟热病毒（CDV）导致脑脊髓炎发作后立即处死的犬中，核转录因子（c-Fos、NFkB）、生长因子（神经生长因子——NGF、脑源性神经营养因子——BDNF）、肽类（脑啡肽、甘丙肽）和谷氨酸转运体（大鼠EAAC1的AA 504-523）的表达情况（通过临床检查、RT-PCR以及血液或脑组织中的病毒RNA检测和脑切片中的CDV免疫组织化学进行评估）。在所有这些受CDV感染的犬中，观察到的神经症状包括无法治疗的癫痫发作，导致成簇癫痫活动和癫痫持续状态。在发作间期，记录到异常精神状态、姿势和步态缺陷，有时还会出现诸如肌阵挛等不自主运动。对5只患有不同疾病且均无癫痫发作的对照犬进行了同样的研究。安乐死后立即取出大脑并固定；从背侧海马体收集的切片进行免疫组织化学处理。通过比较有癫痫发作和无癫痫发作犬的海马体切片，观察到以下变化。发现谷氨酸转运体在整个细胞层均有强烈上调，同时在锥体细胞层X中出现核Fos和NFkB免疫反应性。在所研究的肽类中，我们观察到脑啡肽能纤维略有增加，μ-阿片受体强烈上调，而甘丙肽免疫反应性似乎较弱。最后，NGF和BDNF的表达均强烈上调。BDNF免疫反应性主要定位于锥体细胞的顶端树突。据我们所知，这些数据首次表明，实验性点燃中描述的分子事件在与人类神经病理学有密切相似性的动物物种的自发性病变过程中也会发生。
