Jensen Cathy Joanna, Demol Frauke, Bauwens Romy, Kooijman Ron, Massie Ann, Villers Agnès, Ris Laurence, De Keyser Jacques
Department of Neurology, University Hospital Brussels and Center for Neuroscience, Vrije Universiteit Brussel (VUB), Brussels, Belgium.
Department of Neurobiology, Vlaams Instituut voor Biotechnologie, Leuven, Belgium.
PLoS One. 2016 Oct 24;11(10):e0164721. doi: 10.1371/journal.pone.0164721. eCollection 2016.
In vitro and in vivo studies suggest that the astrocytic adrenergic signalling enhances glycogenolysis which provides energy to be transported to nearby cells and in the form of lactate. This energy source is important for motor and cognitive functioning. While it is suspected that the β2-adrenergic receptor on astrocytes might contribute to this energy balance, it has not yet been shown conclusively in vivo. Inducible astrocyte specific β2-adrenergic receptor knock-out mice were generated by crossing homozygous β2-adrenergic receptor floxed mice (Adrb2flox) and mice with heterozygous tamoxifen-inducible Cre recombinase-expression driven by the astrocyte specific L-glutamate/L-aspartate transporter promoter (GLAST-CreERT2). Assessments using the modified SHIRPA (SmithKline/Harwell/Imperial College/Royal Hospital/Phenotype Assessment) test battery, swimming ability test, and accelerating rotarod test, performed at 1, 2 and 4 weeks, 6 and 12 months after tamoxifen (or vehicle) administration did not reveal any differences in physical health or motor functions between the knock-out mice and controls. However deficits were found in the cognitive ability of aged, but not young adult mice, reflected in impaired learning in the Morris Water Maze. Similarly, long-term potentiation (LTP) was impaired in hippocampal brain slices of aged knock-out mice maintained in low glucose media. Using microdialysis in cerebellar white matter we found no significant differences in extracellular lactate or glucose between the young adult knock-out mice and controls, although trends were detected. Our results suggest that β2-adrenergic receptor expression on astrocytes in mice may be important for maintaining cognitive health at advanced age, but is dispensable for motor function.
体外和体内研究表明，星形胶质细胞的肾上腺素能信号传导可增强糖原分解，糖原分解产生的能量以乳酸的形式输送到附近细胞。这种能量来源对运动和认知功能很重要。虽然怀疑星形胶质细胞上的β2-肾上腺素能受体可能有助于这种能量平衡，但尚未在体内得到确凿证实。通过将纯合的β2-肾上腺素能受体floxed小鼠（Adrb2flox）与由星形胶质细胞特异性L-谷氨酸/L-天冬氨酸转运体启动子（GLAST-CreERT2）驱动的杂合他莫昔芬诱导型Cre重组酶表达的小鼠杂交，产生了诱导型星形胶质细胞特异性β2-肾上腺素能受体敲除小鼠。在给予他莫昔芬（或载体）后1、2和4周、6和12个月，使用改良的SHIRPA（史克必成/哈韦尔/帝国理工学院/皇家医院/表型评估）测试组、游泳能力测试和加速转棒试验进行评估，未发现敲除小鼠与对照组在身体健康或运动功能方面有任何差异。然而，在老年小鼠而非年轻成年小鼠的认知能力中发现了缺陷，这在莫里斯水迷宫中的学习受损中得到体现。同样，在低糖培养基中培养的老年敲除小鼠的海马脑片中，长时程增强（LTP）受损。在小脑白质中使用微透析，我们发现年轻成年敲除小鼠与对照组之间细胞外乳酸或葡萄糖没有显著差异，尽管检测到了趋势。我们的结果表明，小鼠星形胶质细胞上的β2-肾上腺素能受体表达可能对维持老年时的认知健康很重要，但对运动功能来说是可有可无的。
