Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, 2006, Australia.
Discipline of Medicine, Central Clinical School, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia.
Mol Neurobiol. 2023 Jul;60(7):4120-4131. doi: 10.1007/s12035-023-03332-9. Epub 2023 Apr 11.
The role of the lateral geniculate nucleus (LGN) in vision has been extensively studied, yet its extraretinal capacities are still being investigated, including its role in arousal from sleep. The β2 nicotinic acetylcholine receptor (nAChR) subunit is involved in the laminal organisation of the LGN with magnocellular (MC) and parvocellular (PC) neurons. Sudden infant death syndrome (SIDS) occurs during a sleep period and, neuropathologically, is associated with increased neuronal cell death and altered nAChRs. A recent qualitative pilot study from our group implicates the possibility of increased neuronal death/apoptosis in the SIDS LGN. The present study used quantitative analysis to report the baseline expression of apoptotic and nAChR subunits α7 and β2 in the PC and MC layers of the LGN, to determine correlations amongst these markers within layers and across layers, and to evaluate changes in the expression of these markers in the LGN of SIDS infants, along with associations with SIDS risk factors, such as age, sex, cigarette smoke exposure, bed-sharing, and presence of an upper respiratory tract infection (URTI). Tissue was immunohistochemically stained for cell death markers of active caspase-3 (Casp-3) and TUNEL, and for the α7 and β2 nAChR subunits. Amongst 43 cases of sudden and unexpected deaths in infancy (SUDI), classifications included explained deaths (eSUDI, n = 9), SIDS I (n = 5) and SIDS II (n = 29). Results indicated a strong correlation of the apoptotic markers and β2 nAChR subunit between the LGN layers, but not across the markers within the layers. Amongst the diagnostic groups, compared to eSUDI, the SIDS II cases had decreased Casp-3 expression while β2 nAChR expression was increased in both PC and MC layers. Amongst the SIDS risk factors, URTI and bed-sharing were associated with changes in neuronal death but not in the α7 and β2 markers. In conclusion, our findings do not support a role for the α7 and β2 nAChRs in apoptotic regulation of the LGN layers during infancy. However, for SIDS victims, an inverse correlation between the changes for markers of apoptosis and the β2 nAChR subunit expression suggests altered LGN function.
外侧膝状体（LGN）在视觉中的作用已得到广泛研究，但它的视网膜外功能仍在研究中，包括其在睡眠中觉醒的作用。β2 烟碱型乙酰胆碱受体（nAChR）亚基参与 LGN 的层状组织，与大细胞（MC）和小细胞（PC）神经元有关。婴儿猝死综合征（SIDS）发生在睡眠期间，从神经病理学角度来看，它与神经元细胞死亡增加和 nAChR 改变有关。我们小组的一项最近定性试点研究表明，SIDS LGN 中可能存在神经元死亡/凋亡增加的可能性。本研究使用定量分析报告了 LGN 中 PC 和 MC 层中凋亡和 nAChR 亚基 α7 和 β2 的基线表达，以确定这些标志物在层内和跨层之间的相关性，并评估 SIDS 婴儿 LGN 中这些标志物表达的变化，以及与 SIDS 风险因素（如年龄、性别、吸烟暴露、同床睡和上呼吸道感染（URTI））的关联。组织用细胞死亡标志物活性半胱氨酸天冬氨酸蛋白酶-3（Casp-3）和 TUNEL 以及 α7 和 β2 nAChR 亚基进行免疫组织化学染色。在 43 例婴儿突发和意外死亡（SUDI）中，分类包括解释性死亡（eSUDI，n=9）、SIDS I（n=5）和 SIDS II（n=29）。结果表明，LGN 层之间的凋亡标志物和 β2 nAChR 亚基之间存在强烈相关性，但在层内标志物之间没有相关性。在诊断组中，与 eSUDI 相比，SIDS II 病例的 Casp-3 表达降低，而 PC 和 MC 层的 β2 nAChR 表达增加。在 SIDS 风险因素中，URTI 和同床睡与神经元死亡的变化有关，但与 α7 和 β2 标志物无关。总之，我们的研究结果不支持在婴儿期 LGN 层的凋亡调节中 α7 和 β2 nAChR 起作用。然而，对于 SIDS 患者，凋亡标志物和 β2 nAChR 亚基表达之间的变化呈负相关，这表明 LGN 功能发生改变。
