Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin, Kerala, India.
J Neurosci Res. 2013 Sep;91(9):1203-14. doi: 10.1002/jnr.23243. Epub 2013 Jul 3.
γ-Aminobutyric acid (GABA)- and serotonin (5-HT)-mediated cell signaling, neuronal survival enhancement, and reduced neuronal death in brainstem during liver injury followed by active liver regeneration have a critical role in maintaining routine bodily functions. In the present study, GABAB and 5-HT2A receptor functional regulation, interrelated actions of neuronal survival factors, and expression of apoptotic factors in the brainstem during GABA and 5-HT chitosan nanoparticles-induced active liver regeneration in partially hepatectomized rats were evaluated. Partially hepatectomized rats were treated with the nanoparticles, and receptor assays and confocal microscopic studies of GABAB and 5-HT2A receptors, gene expression studies of GABAB and 5-HT2A receptors, nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), Akt-1, phospholipase C, Bax, and caspase-8 were performed with the brainstems of experimental animals. A significant decrease in GABAB and 5-HT2A receptor numbers and gene expressions denoted a homeostatic adjustment by the brain to trigger the sympathetic innervations during elevated DNA synthesis in the liver. The neuronal apoptosis resulting from the loss of liver function after partial hepatectomy was minimized by nanoparticle treatment in rats compared with rats with no treatment during regeneration. This was confirmed from the gene expression patterns of NF-κB, TNF-α, Akt-1, phospholipase C, Bax, and caspase-8. The present study revealed the potential of GABA and 5-HT chitosan nanoparticles for increasing neuronal survival in the brainstem during liver injury following regeneration, which avoids many neuropsychiatric problems.
γ-氨基丁酸（GABA）和 5-羟色胺（5-HT）介导的细胞信号转导、增强神经元存活以及肝损伤后脑干中神经元死亡减少在维持常规身体功能方面起着关键作用。在本研究中，评估了 GABA 和 5-HT 壳聚糖纳米颗粒诱导部分肝切除大鼠活跃肝再生期间脑干中 GABAB 和 5-HT2A 受体的功能调节、神经元存活因子的相互作用以及凋亡因子的表达。部分肝切除大鼠用纳米颗粒处理，并对 GABAB 和 5-HT2A 受体进行受体测定和共聚焦显微镜研究，GABAB 和 5-HT2A 受体、核因子-κB（NF-κB）、肿瘤坏死因子-α（TNF-α）、Akt-1、磷脂酶 C、Bax 和 caspase-8 的基因表达研究在实验动物的脑干中进行。GABAB 和 5-HT2A 受体数量和基因表达的显著减少表示大脑通过触发交感神经支配来进行稳态调整，以在肝脏中升高的 DNA 合成期间触发交感神经支配。与再生期间未治疗的大鼠相比，纳米颗粒治疗可最大程度地减少大鼠部分肝切除后肝功能丧失引起的神经元凋亡。这从 NF-κB、TNF-α、Akt-1、磷脂酶 C、Bax 和 caspase-8 的基因表达模式得到证实。本研究揭示了 GABA 和 5-HT 壳聚糖纳米颗粒在再生后肝损伤期间增加脑干中神经元存活的潜力，从而避免了许多神经精神问题。
