Saleh Tarek M, Connell Barry J, McQuaid Tim, Cribb Alastair E
Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PEI, Canada C1A 4P3.
Brain Res. 2003 Nov 14;990(1-2):58-65. doi: 10.1016/s0006-8993(03)03387-0.
Estrogen has previously been shown to significantly change sympathetic and parasympathetic system output via an action within the central nuclei responsible for regulating autonomic tone. These estrogen-induced changes were observed within 30 min of systemic administration and could be blocked by the direct microinjection of the estrogen receptor antagonist, ICI 182780, into the parabrachial nucleus (PBN) of the pons. In the present investigation, we sought to determine the possible mechanism(s) by which estrogen produced these rapid changes in autonomic tone by determining if estrogen modulates neuronal excitability within the PBN. Male Sprague-Dawley rats were anaesthetized with Inactin (sodium thiobutabarbitol, 100 mg/kg) and instrumented for the intravenous injection of estrogen and placed in a stereotaxic frame for the insertion of a microdialysis probe or glass recording electrode into the PBN. In the first experiment, we sought to determine the local concentration of estrogen in the cerebrospinal fluid in the PBN following systemic injection of estrogen. In the second experiment, we sought to determine the functional significance of systemic estrogen injection on neuronal activity and amino acid neurotransmitter levels in the PBN. Systemic estrogen injection resulted in a significant increase in local estrogen concentration in the PBN which corresponded to a decrease in neuronal excitability and extracellular glutamate levels while increasing GABA levels in the PBN. These results suggest that estrogen decreases neuronal excitability in the PBN by modulating synaptic transmission via an increased release of GABA and a decreased release of glutamate.
雌激素此前已被证明可通过作用于负责调节自主神经张力的中枢核团，显著改变交感神经系统和副交感神经系统的输出。在全身给药后30分钟内观察到了这些雌激素诱导的变化，并且通过将雌激素受体拮抗剂ICI 182780直接微量注射到脑桥的臂旁核（PBN）中，可以阻断这些变化。在本研究中，我们试图通过确定雌激素是否调节PBN内的神经元兴奋性，来确定雌激素产生这些自主神经张力快速变化的可能机制。雄性Sprague-Dawley大鼠用氯胺酮（硫代丁巴比妥钠，100mg/kg）麻醉，安装用于静脉注射雌激素的装置，并置于立体定位框架中，以便将微透析探针或玻璃记录电极插入PBN。在第一个实验中，我们试图确定全身注射雌激素后PBN中脑脊液中雌激素的局部浓度。在第二个实验中，我们试图确定全身注射雌激素对PBN中神经元活动和氨基酸神经递质水平的功能意义。全身注射雌激素导致PBN中局部雌激素浓度显著增加，这对应于神经元兴奋性降低和细胞外谷氨酸水平降低，同时PBN中GABA水平升高。这些结果表明，雌激素通过增加GABA释放和减少谷氨酸释放来调节突触传递，从而降低PBN中的神经元兴奋性。
