Al-Abdulla N A, Martin L J
Department of Pathology, Division of Neuropathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA.
Neuroscience. 2002;115(1):7-14. doi: 10.1016/s0306-4522(02)00363-9.
The cytological responses of thalamic interneurons to selective degeneration of thalamocortical projection neurons after cortical damage in the adult brain are poorly understood. We used a unilateral neocortical lesion model (occipital cortex ablation) in the adult rat to test the hypothesis that interneurons and projection neurons in the lateral geniculate nucleus undergo distinct forms of degeneration. In situ nuclear DNA fragmentation in neurons in the lateral geniculate occurs maximally at 7 days postlesion. Geniculocortical projection neurons that are identified by the retrograde tracer Fluorogold die primarily with a morphology of endstage apoptosis prominent at 7 days postlesion. In contrast, interneurons, identified by their particular nuclear ultrastructure and by glutamic acid decarboxylase immunoreactivity, undergo an atrophic vacuolar pathology starting early during the period of projection neuron death and peaking after the projection neuron death is complete. This degeneration of interneurons is transient, because these neurons exhibit structural recovery and their numbers are not changed significantly postlesion. A rare subset of interneurons (less than one in 100 interneurons and less than one in 100 apoptotic cells) undergoes apoptosis concurrently with the projection neurons. We conclude that different types of neurons within the same thalamic nucleus respond differently to focal cortical target deprivation. Unlike the apoptosis-prone projection neurons, most interneurons undergo transient transsynaptic atrophy and recovery rather than cell death. Nevertheless, a small subset of lateral geniculate interneurons undergoes transsynaptic apoptosis in response to projection neuron apoptosis. The pathological responses of thalamic neurons to cortical trauma vary depending on cell type.
在成体大脑皮质损伤后，丘脑皮质投射神经元选择性变性时丘脑中间神经元的细胞学反应仍知之甚少。我们使用成年大鼠的单侧新皮质损伤模型（枕叶皮质切除）来检验外侧膝状核中的中间神经元和投射神经元会经历不同形式变性的假说。外侧膝状核神经元原位核DNA片段化在损伤后7天达到峰值。由逆行示踪剂荧光金标记的膝状体皮质投射神经元主要以损伤后7天显著的终末期凋亡形态死亡。相比之下，通过其特定核超微结构和谷氨酸脱羧酶免疫反应性鉴定的中间神经元，在投射神经元死亡期间早期开始出现萎缩性空泡病变，并在投射神经元死亡完全后达到峰值。中间神经元的这种变性是短暂的，因为这些神经元表现出结构恢复，并且其数量在损伤后没有显著变化。一小部分罕见的中间神经元（每100个中间神经元中不到1个，每100个凋亡细胞中不到1个）与投射神经元同时发生凋亡。我们得出结论，同一丘脑核内的不同类型神经元对局部皮质靶标剥夺的反应不同。与易发生凋亡的投射神经元不同，大多数中间神经元经历短暂的跨突触萎缩和恢复，而不是细胞死亡。然而，一小部分外侧膝状核中间神经元会因投射神经元凋亡而发生跨突触凋亡。丘脑神经元对皮质创伤的病理反应因细胞类型而异。
