Ogier Michael, Bricca Giampiero, Bader Michael, Bezin Laurent
INSERM U1028, CNRS UMR5292, University Claude Bernard Lyon 1, Lyon Neuroscience Research Center, Team TIGER, Lyon, France.
Institute for Epilepsy, IDEE, Lyon, France.
CNS Neurosci Ther. 2016 Mar;22(3):230-7. doi: 10.1111/cns.12488. Epub 2016 Jan 18.
Transgenic TGR(ASrAOGEN)680 (TGR) rats with specific downregulation of glial angiotensinogen (AOGEN) synthesis develop cardiovascular deficits, anxiety, altered response to stress, and depression. Here, we evaluated whether these deficits are associated with alteration of the integrity of the noradrenergic system originating from locus coeruleus (LC) neurons.
Adult TGR rats were compared to control Sprague Dawley rats in terms of the following: tissue levels of transcripts encoding noradrenergic markers, tissue tyrosine hydroxylase (TH) protein level, in vivo TH activity, density of TH-containing fibers, behavioral response to novelty, locomotor activity, and polysomnography.
TH expression was increased in the LC of TGR rats compared to controls. In LC terminal fields, there was an increase in density of TH-containing fibers in TGR rats that was associated with an elevation of in vivo TH activity. TGR rats also displayed locomotor hyperactivity in response to novelty. Moreover, polysomnographic studies indicated that daily paradoxical sleep duration was increased in TGR rats and that the paradoxical sleep rebound triggered by total sleep deprivation was blunted in these rats.
Altogether, these results suggest that disruption of astroglial AOGEN synthesis leads to cardiovascular, cognitive, behavioral, and sleep disorders that might be partly due to LC dysfunction.
胶质血管紧张素原（AOGEN）合成特异性下调的转基因TGR（ASrAOGEN）680（TGR）大鼠出现心血管缺陷、焦虑、应激反应改变和抑郁。在此，我们评估这些缺陷是否与源自蓝斑（LC）神经元的去甲肾上腺素能系统完整性改变有关。
将成年TGR大鼠与对照Sprague Dawley大鼠在以下方面进行比较：编码去甲肾上腺素能标志物的转录本的组织水平、组织酪氨酸羟化酶（TH）蛋白水平、体内TH活性、含TH纤维的密度、对新奇事物的行为反应、运动活动和多导睡眠图。
与对照组相比，TGR大鼠LC中的TH表达增加。在LC终末区域，TGR大鼠中含TH纤维的密度增加，这与体内TH活性升高有关。TGR大鼠对新奇事物也表现出运动亢进。此外，多导睡眠图研究表明，TGR大鼠的每日异相睡眠时间增加，并且这些大鼠中由完全睡眠剥夺触发的异相睡眠反弹减弱。
总之，这些结果表明星形胶质细胞AOGEN合成的破坏导致心血管、认知、行为和睡眠障碍，这可能部分归因于LC功能障碍。
