Abstract
Homomeric α7 nicotinic acetylcholine receptors (nAChRs) are abundantly expressed in the central and peripheral nervous system (CNS and PNS, respectively), and spinal cord. In addition, expression and functional responses have been reported in non-neuronal tissue. In the nervous system, α7 nAChR subunit expression appears early during embryonic development and is often transiently upregulated, but little is known about their prenatal expression outside of the nervous system. For understanding potential short-term and long-term effects of gestational nicotine exposure, it is important to know the temporal and spatial expression of α7 nAChRs throughout the body. To that end, we studied the expression of α7 nAChR subunit mRNA using highly sensitive isotopic in situ hybridization in embryonic and neonatal whole-body mouse sections starting at gestational day 13. The results revealed expression of α7 mRNA as early as embryonic day 13 in the PNS, including dorsal root ganglia, parasympathetic and sympathetic ganglia, with the strongest expression in the superior cervical ganglion, and low to moderate levels were detected in brain and spinal cord, respectively, which rapidly increased in intensity with embryonic age. In addition, robust α7 mRNA expression was detected in the adrenal medulla, and low to moderate expression in selected peripheral tissues during embryonic development, potentially related to cells derived from the neural crest. Little or no mRNA expression was detected in thymus or spleen, sites of immune cell maturation. The results suggest that prenatal nicotine exposure could potentially affect the nervous system with limited effects in non-neural tissues.
Highlights
Nicotinic acetylcholine receptors are ligand gated pentameric cation channels, which were first identified in Torpedo electric organ, and are found in vertebrate and non-vertebrate animals (Changeux, 2012)
We began our analysis at E13 because it was previously demonstrated that at this age, low levels of α7 nicotinic acetylcholine receptors (nAChRs) mRNA expression first appear in several regions of the rat brain (Broide et al, 1995; Adams et al, 2002)
The current study focused on α7 nAChR mRNA expression in embryonic and neonatal tissues
Summary
Nicotinic acetylcholine receptors (nAChRs) are ligand gated pentameric cation channels, which were first identified in Torpedo electric organ, and are found in vertebrate and non-vertebrate animals (Changeux, 2012). The nAChRs can be broadly classified into muscle and neuronal type nAChRs, based on the compositions of the subunits that form the ion channel. The neuronal type nAChRs exhibit great diversity, and heteromeric receptors are formed by various compositions of alpha (α2–α10) and non-alpha (β2–β4) subunits. In the brain and spinal cord, α4 and β2 subunits are broadly expressed, and form the widely distributed neuronal heteromeric nAChR that displays high affinity for nicotine, and is primarily located on presynaptic terminals (Papke, 2014). Homomeric α7 nAChRs, which are distinguished from neuronal heteromeric nAChRs by their high-affinity binding to α-Bungarotoxin (α-BTX), are abundantly expressed in the CNS and spinal cord, where they are located at pre-and postsynaptic sites (Tribollet et al, 2004). Homomeric α7 nAChRs are detected in the periphery, but their functional role in either the PNS or ENS, during development, is still unclear
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