Damborsky Joanne C, Griffith William H, Winzer-Serhan Ursula H
Department of Neuroscience & Experimental Therapeutics, College of Medicine, Health Science Center, Texas A&M University, USA.
Department of Neuroscience & Experimental Therapeutics, College of Medicine, Health Science Center, Texas A&M University, USA.
Neuropharmacology. 2015 Jan;88:187-98. doi: 10.1016/j.neuropharm.2014.06.010. Epub 2014 Jun 17.
Developmental exposure to nicotine has been linked to long-lasting changes in synaptic transmission which may contribute to behavioral abnormalities seen in offspring of women who smoke during pregnancy. Here, we examined the long-lasting effects of developmental nicotine exposure on glutamatergic and GABAergic neurotransmission, and on acute nicotine-induced glutamate and GABA release in the adult hippocampus, a structure important in cognitive and emotional behaviors. We utilized a chronic neonatal nicotine treatment model to administer nicotine (6 mg/kg/day) to rat pups from postnatal day (P) 1-7, a period that falls developmentally into the third human trimester. Using whole-cell voltage clamp recordings from CA1 pyramidal neurons in hippocampal slices, we measured excitatory and inhibitory postsynaptic currents in neonatally control- and nicotine-treated young adult males. Neonatal nicotine exposure significantly increased AMPA receptor-mediated spontaneous and evoked excitatory signaling, with no change in glutamate release probability in adults. Conversely, there was no increase in spontaneous GABAergic neurotransmission in nicotine-males. Chronic neonatal nicotine treatment had no effect on acute nicotine-stimulated glutamate release in adults, but acute nicotine-stimulated GABA release was significantly attenuated. Thus, neonatal nicotine exposure results in a persistent net increase in excitation and a concurrent loss of nicotinic acetylcholine receptor (nAChR)-mediated regulation of presynaptic GABA but not glutamate release, which would exacerbate excitation following endogenous or exogenous nAChR activation. Our data underscore an important role for nAChRs in hippocampal excitatory synapse development, and suggest selective long-term changes at specific presynaptic nAChRs which together could explain some of the behavioral abnormalities associated with maternal smoking.
发育过程中接触尼古丁与突触传递的长期变化有关，这可能导致孕期吸烟女性后代出现行为异常。在此，我们研究了发育过程中接触尼古丁对谷氨酸能和γ-氨基丁酸能神经传递的长期影响，以及对成年海马体中急性尼古丁诱导的谷氨酸和γ-氨基丁酸释放的影响，海马体是认知和情感行为中的重要结构。我们利用慢性新生儿尼古丁治疗模型，从出生后第1天（P1）至第7天给幼鼠注射尼古丁（6毫克/千克/天），这一时期在发育上相当于人类孕期的第三个月。通过对海马切片中CA1锥体神经元进行全细胞电压钳记录，我们测量了新生期接受对照处理和尼古丁处理的成年雄性大鼠的兴奋性和抑制性突触后电流。新生期接触尼古丁显著增加了AMPA受体介导的自发性和诱发性兴奋性信号，而成年大鼠的谷氨酸释放概率没有变化。相反，尼古丁处理的雄性大鼠自发性γ-氨基丁酸能神经传递没有增加。慢性新生儿尼古丁处理对成年大鼠急性尼古丁刺激的谷氨酸释放没有影响，但急性尼古丁刺激的γ-氨基丁酸释放显著减弱。因此，新生期接触尼古丁导致兴奋性持续净增加，同时烟碱型乙酰胆碱受体（nAChR）介导的对突触前γ-氨基丁酸而非谷氨酸释放的调节丧失，这会在内源性或外源性nAChR激活后加剧兴奋。我们的数据强调了nAChR在海马兴奋性突触发育中的重要作用，并表明特定突触前nAChR存在选择性长期变化，这共同可以解释一些与母亲吸烟相关的行为异常。
