Cell death in the lateral geniculate nucleus, and its possible relationship with nicotinic receptors and sudden infant death syndrome (SIDS)

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 beta 2 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 alpha 7 and beta 2 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 alpha 7 and beta 2 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 beta 2 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 beta 2 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 alpha 7 and beta 2 markers. In conclusion, our findings do not support a role for the alpha 7 and beta 2 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 beta 2 nAChR subunit expression suggests altered LGN function.

Automated summary

The role of the LGN in vision and sleep arousal is being investigated, and a recent study suggests a link between neuronal death/apoptosis and SIDS in the LGN. This study quantitatively analyzes the expression of apoptotic markers and nAChR subunits alpha 7 and beta 2 in the LGN of SIDS infants, and evaluates their associations with SIDS risk factors. Results indicate a correlation between apoptotic markers and beta 2 nAChR subunit expression in the LGN layers, with different expression patterns in SIDS cases and changes associated with SIDS risk factors.