title: Astrocytic β2 Adrenergic Receptor Gene Deletion Affects Memory in Aged Mice.
abstract: 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.
authors: 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.
authors: Cathy Joanna
authors: CJ
authors: Jensen
authors: Department of Neurology, University Hospital Brussels and Center for Neuroscience, Vrije Universiteit Brussel (VUB), Brussels, Belgium.
authors: Frauke
authors: F
authors: Demol
authors: Center for Neurosiences, Vrije Universiteit Brussel, Brussels, Belgium.
authors: Romy
authors: R
authors: Bauwens
authors: Center for Neurosiences, Vrije Universiteit Brussel, Brussels, Belgium.
authors: Ron
authors: R
authors: Kooijman
authors: Center for Neurosiences, Vrije Universiteit Brussel, Brussels, Belgium.
authors: Ann
authors: A
authors: Massie
authors: Department of Neuroscience, Health, University of Mons, Mons, Belgium.
authors: Agnès
authors: A
authors: Villers
authors: Department of Neuroscience, Health, University of Mons, Mons, Belgium.
authors: Laurence
authors: L
authors: Ris
authors: Department of Neurology, University Hospital Brussels and Center for Neuroscience, Vrije Universiteit Brussel (VUB), Brussels, Belgium.|Department of Neurology, University Medical Center Groningen, Groningen, The Netherlands.
authors: Jacques
authors: J
authors: De Keyser
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D017353:Gene Deletion; D018782:Maze Learning; D008568:Memory; D051379:Mice; D018345:Mice, Knockout; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics* / Q000378:metabolism
chemical_list: D018343:Receptors, Adrenergic, beta-2