Prenatal cigarette smoke exposure effects on apoptotic and nicotinic acetylcholine receptor expression in the infant mouse brainstem

Infants exposed to cigarette smoked during pregnancy into infancy have increased respiratory and cardiac abnormalities. Nicotine, the major neurotoxic component of cigarette smoke, induces its actions by binding to nicotinic acetylcholine receptors (nAChR), with one downstream effect being increased apoptosis. Using a pre- into post- natal cigarette smoke exposure mouse model (SE), we studied the immunohistochemical expression of nAChR subunits alpha 2, alpha 3, alpha 4, alpha 5, alpha 7, alpha 9, beta 1 and beta 2 and two markers of apoptosis, active caspase-3 and TUNEL, in seven nuclei of the medulla and facial nucleus of the pons in male mice. Pups of dams exposed to two cigarettes (nicotine <= 1.2 mg, CO <= 15 mg) twice daily for six weeks prior to mating, during gestation and lactation (n = 5; SE), were compared to pups exposed to air under the same condition (n = 5; SHAM) at P20. Results showed that the hypoglossal nucleus had increased alpha 3, alpha 4, alpha 7, alpha 9, Casp-3 and TUNEL, dorsal motor nucleus of the vagus had increased alpha 3, alpha 5, alpha 7, beta 1 and Casp-3, nucleus of the solitary tract had increased alpha 3 but decreased alpha 4, alpha 5, beta 1 and apoptosis, cuneate nucleus had increased alpha 3, beta 2 and Casp- 3, but decreased alpha 5, nucleus of the spinal trigeminal tract had increased alpha 3, alpha 7, beta 1, lateral reticular nucleus had decreased beta 1, inferior olivary nucleus had increased beta 1 but decreased apoptosis, and the facial had increased alpha 2, alpha 3 and alpha 7. This is the first study to demonstrate that nAChR subunits are affected following pre- into post-natal SE and that they simultaneously coincided with changes in apoptotic expression. (C) 2015 Elsevier Inc. All rights reserved.