Ohbuchi Toyoaki, Yokoyama Toru, Saito Takeshi, Hashimoto Hirofumi, Suzuki Hitoshi, Otsubo Hiroki, Fujihara Hiroaki, Suzuki Hideaki, Ueta Yoichi
Department of Physiology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan.
Brain Res. 2009 Mar 3;1258:34-42. doi: 10.1016/j.brainres.2008.12.057. Epub 2008 Dec 31.
Body fluid balance requires the release of arginine vasopressin (AVP) from the neurohypophysis. The hypothalamic supraoptic nucleus (SON) is one of the major sites for the synthesis of AVP, and secretion of AVP is controlled by the electrical activities of magnocellular neurosecretory cells (MNCs), which in turn are regulated by neuronal excitatory glutamatergic and inhibitory GABAergic inputs and humoral factors such as plasma osmolality. Previous studies have shown that brain-derived neurotrophic factor (BDNF) mRNA was increased by osmotic stress in the rat SON. In the present study, the effects of BDNF on excitatory and inhibitory synaptic inputs were examined in the MNCs of rat SON, using the whole-cell patch-clamp technique in in vitro brain slice preparations. BDNF application caused a significant reduction in the frequency and amplitude of the spontaneous inhibitory postsynaptic currents of the MNCs without affecting the spontaneous excitatory postsynaptic currents. Next, whole-cell patch-clamp recordings from dissociated SON MNCs expressing AVP-enhanced green fluorescent protein (eGFP) transgene revealed that the amplitude of GABA-induced currents were significantly smaller after BDNF treatment. Moreover, multi-cell reverse transcriptase-polymerase chain reaction (RT-PCR) experiments revealed the expression of TrkB mRNA in AVP-eGFP neurons. These results suggest that BDNF in the rat SON may decrease the postsynaptic GABAergic activity and may be involved in the regulatory mechanisms of body fluid homeostasis.
体液平衡需要神经垂体释放精氨酸加压素（AVP）。下丘脑视上核（SON）是AVP合成的主要部位之一，AVP的分泌受大细胞神经分泌细胞（MNCs）电活动的控制，而MNCs的电活动又受神经元兴奋性谷氨酸能和抑制性γ-氨基丁酸能输入以及血浆渗透压等体液因子的调节。先前的研究表明，大鼠SON中的脑源性神经营养因子（BDNF）mRNA在渗透压应激下会增加。在本研究中，利用体外脑片制备中的全细胞膜片钳技术，研究了BDNF对大鼠SON的MNCs中兴奋性和抑制性突触输入的影响。应用BDNF可使MNCs的自发性抑制性突触后电流的频率和幅度显著降低，而不影响自发性兴奋性突触后电流。接下来，对表达AVP增强型绿色荧光蛋白（eGFP）转基因的离体SON MNCs进行全细胞膜片钳记录，结果显示BDNF处理后GABA诱导电流的幅度显著减小。此外，多细胞逆转录聚合酶链反应（RT-PCR）实验揭示了TrkB mRNA在AVP-eGFP神经元中的表达。这些结果表明，大鼠SON中的BDNF可能会降低突触后GABA能活性，并可能参与体液稳态的调节机制。
