Vivekanandarajah Arunnjah, Waters Karen A, Machaalani Rita
The BOSCH Institute, NSW 2006, Australia; Department of Medicine, Blackburn Building, DO6, University of Sydney, NSW 2006, Australia.
The BOSCH Institute, NSW 2006, Australia; Department of Medicine, Blackburn Building, DO6, University of Sydney, NSW 2006, Australia; The Children's Hospital, Westmead Sydney, NSW 2145, Australia.
Int J Dev Neurosci. 2015 Dec;47(Pt B):183-91. doi: 10.1016/j.ijdevneu.2015.09.007. Epub 2015 Oct 9.
Postnatal exposure to cigarette smoke during infancy is associated with increased number of respiratory illnesses, impaired pulmonary function, and the occurrence of Sudden Infant Death Syndrome (SIDS). It is also associated with reduced cognitive functioning and attention deficits in childhood. Nicotine, the major neurotoxic component of cigarette smoke, induces its actions by binding to nicotinic acetylcholine receptors (nAChR). Using a piglet model of postnatal nicotine exposure, we studied the immunohistochemical expression of nAChR subunits α2, α3, α4, α5, α7, α9, β1 and β2 in the brainstem medulla and the hippocampus, given the role of these structures in cardiorespiratory control and cognition, respectively. We compared piglets exposed postnatally to 2mg/kg/day nicotine for 14 days (n=14: 7 males: 7 females) to controls (n=14: 7 males: 7 females). In the hippocampus, decreased expression was seen for α3 in CA1 (p=0.017), α9 in CA1 (p<0.001) and CA2 (p<0.001), β1 in CA1 (p=0.001) and CA2 (p=0.001) and β2 in CA3 (p=0.036). In the medulla, the nucleus of the spinal trigeminal tract had increased α2 and α4; vestibular nucleus increased α2 and α3, and decreased α4; hypoglossal decreased α3 and β1; dorsal motor nucleus of the vagus decreased α4 and β1. This is the first demonstration that non-classical nAChR subunits are affected by postnatal nicotine in the developing brain, and the implications are discussed.
婴儿期暴露于香烟烟雾与呼吸道疾病数量增加、肺功能受损以及婴儿猝死综合征（SIDS）的发生有关。它还与儿童期认知功能下降和注意力缺陷有关。尼古丁是香烟烟雾中的主要神经毒性成分，通过与烟碱型乙酰胆碱受体（nAChR）结合发挥作用。鉴于脑干延髓和海马体分别在心肺控制和认知中的作用，我们利用出生后尼古丁暴露的仔猪模型，研究了nAChR亚基α2、α3、α4、α5、α7、α9、β1和β2在脑干延髓和海马体中的免疫组化表达。我们将出生后14天每天暴露于2mg/kg尼古丁的仔猪（n = 14：7只雄性，7只雌性）与对照组（n = 14：7只雄性，7只雌性）进行比较。在海马体中，CA1区的α3（p = 0.017）、CA1区和CA2区的α9（p < 0.001）、CA1区和CA2区的β1（p = 0.001）以及CA3区的β2（p = 0.036）表达降低。在延髓中，三叉神经脊束核的α2和α4增加；前庭核的α2和α3增加，但α4减少；舌下神经核的α3和β1减少；迷走神经背运动核的α4和β1减少。这是首次证明非经典nAChR亚基在发育中的大脑中受到出生后尼古丁的影响，并对其影响进行了讨论。
