title: The GLP-1 Receptor Agonist Liraglutide Improves Memory Function and Increases Hippocampal CA1 Neuronal Numbers in a Senescence-Accelerated Mouse Model of Alzheimer's Disease.
abstract: Recent studies indicate that glucagon-like peptide 1 (GLP-1) receptor agonists, currently used in the management of type 2 diabetes, exhibit neurotrophic and neuroprotective effects in amyloid-β (Aβ) toxicity models of Alzheimer's disease (AD). We investigated the potential pro-cognitive and neuroprotective effects of the once-daily GLP-1 receptor agonist liraglutide in senescence-accelerated mouse prone 8 (SAMP8) mice, a model of age-related sporadic AD not dominated by amyloid plaques. Six-month-old SAMP8 mice received liraglutide (100 or 500 μg/kg/day, s.c.) or vehicle once daily for 4 months. Vehicle-dosed age-matched 50% back-crossed as well as untreated young (4-month-old) SAMP8 mice were used as control groups for normal memory function. Vehicle-dosed 10-month-old SAMP8 mice showed significant learning and memory retention deficits in an active-avoidance T-maze, as compared to both control groups. Also, 10-month-old SAMP8 mice displayed no immunohistological signatures of amyloid-β plaques or hyperphosphorylated tau, indicating the onset of cognitive deficits prior to deposition of amyloid plaques and neurofibrillary tangles in this AD model. Liraglutide significantly increased memory retention and total hippocampal CA1 pyramidal neuron numbers in SAMP8 mice, as compared to age-matched vehicle-dosed SAMP8 mice. In conclusion, liraglutide delayed or partially halted the progressive decline in memory function associated with hippocampal neuronal loss in a mouse model of pathological aging with characteristics of neurobehavioral and neuropathological impairments observed in early-stage sporadic AD.
authors: Gubra, Hoersholm, Denmark.
authors: Henrik H
authors: HH
authors: Hansen
authors: Gubra, Hoersholm, Denmark.
authors: Katrine
authors: K
authors: Fabricius
authors: Gubra, Hoersholm, Denmark.
authors: Pernille
authors: P
authors: Barkholt
authors: St. Louis University, Division of Geriatrics, St. Louis, MO, USA.
authors: Michael L
authors: ML
authors: Niehoff
authors: St. Louis University, Division of Geriatrics, St. Louis, MO, USA.|St. Louis University School of Medicine, Division of Endocrinology, St. Louis University, St. Louis, MO, USA.
authors: John E
authors: JE
authors: Morley
authors: Gubra, Hoersholm, Denmark.
authors: Jacob
authors: J
authors: Jelsing
authors: Diabetes Research, Novo Nordisk A/S, Maaloev, Denmark.
authors: Charles
authors: C
authors: Pyke
authors: Diabetes Research, Novo Nordisk A/S, Maaloev, Denmark.
authors: Lotte Bjerre
authors: LB
authors: Knudsen
authors: St. Louis University, Division of Geriatrics, St. Louis, MO, USA.|Research and Development, Veterans Affairs Medical Center, St. Louis, MO, USA.
authors: Susan A
authors: SA
authors: Farr
authors: Gubra, Hoersholm, Denmark.
authors: Niels
authors: N
authors: Vrang
mesh_terms: D000367:Age Factors; D000375:Aging / Q000235:genetics; D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002452:Cell Count; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D007004:Hypoglycemic Agents / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D000069450:Liraglutide / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains
chemical_list: D016229:Amyloid beta-Peptides; D007004:Hypoglycemic Agents; D000069450:Liraglutide
keywords: Alzheimer’s disease; GLP-1 receptor agonist; SAMP8 mouse; hippocampus; liraglutide; memory function; neuroprotection; stereology