title: In vivo administration of granulocyte colony-stimulating factor restores long-term depression in hippocampal slices prepared from transgenic APP/PS1 mice.
abstract: Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic cytokine that also possesses neurotrophic and antiapoptotic properties. G-CSF has been reported to decrease amyloid burden significantly, promote hippocampal neurogenesis, and improve spatial learning in a mouse model of Alzheimer's disease. To understand better the effects of G-CSF on hippocampal-dependent learning, the present study focused on electrophysiological correlates of neuroplasticity, long-term potentiation (LTP), and long-term depression (LTD). Two cohorts of transgenic APP/PS1 mice, with or without prior bone marrow transplantation from Tg GFP mice, were treated in vivo for 2 weeks with G-CSF or vehicle. After completion of the treatments, hippocampal slices were prepared for electrophysiological studies of LTP and LTD. LTP was induced and maintained in both G-CSF-treated and vehicle-treated groups of Tg APP/PS1. In contrast, LTD could not be induced in vehicle-treated Tg APP/PS1 mice, but G-CSF treatment restored LTD. The LTP and LTD results obtained from the cohort of bone marrow-grafted Tg APP/PS1 mice did not differ from those from nongrafted Tg APP/PS1 mice. The mechanism by which G-CSF restores LTD is not known, but it is possible that its capacity to reduce amyloid plaques results in increased soluble oligomers of amyloid-β (A-β), which in turn may facilitate LTD. This mechanism would be consistent with the recent report that soluble A-β oligomers promote LTD in hippocampal slices.
authors.affiliation: James Haley VA Hospital, Tampa, Florida; Department of Neurology, University of South Florida, Tampa, Florida.
authors.forename: Shijie
authors.initials: S
authors.lastname: Song
authors.forename: Xinming
authors.initials: X
authors.lastname: Wang
authors.forename: Vasyl
authors.initials: V
authors.lastname: Sava
authors.forename: Edwin J
authors.initials: EJ
authors.lastname: Weeber
authors.forename: Juan
authors.initials: J
authors.lastname: Sanchez-Ramos
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000503:physiopathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D004195:Disease Models, Animal; D004594:Electrophysiology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D036881:Long-Term Synaptic Depression / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D053764:Presenilin-1 / Q000235:genetics
chemical_list: D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1; D016179:Granulocyte Colony-Stimulating Factor
keywords: electrophysiology; hematopoietic growth factor; neuroplasticity