title: Increased hippocampal CA1 density of serotonergic terminals in a triple transgenic mouse model of Alzheimer's disease: an ultrastructural study.
abstract: Alzheimer's disease (AD) is a neurodegenerative pathology that deteriorates mnesic functions and associated brain regions including the hippocampus. Serotonin (5-HT) has an important role in cognition. We recently demonstrated an increase in 5-HT transporter (SERT) fibre density in the hippocampal CA1 in an AD triple transgenic mouse model (3xTg-AD). Here, we analyse the ultrastructural localisation, distribution and numerical density (N(v)) of hippocampal SERT axons (SERT-Ax) and terminals (SERT-Te) and their relationship with SERT fibre sprouting and altered synaptic N(v) in 3xTg-AD compared with non-transgenic control mice. 3xTg-AD animals showed a significant increase in SERT-Te N(v) in CA1 at both, 3 (95%) and 18 months of age (144%), being restricted to the CA1 stratum moleculare (S. Mol; 227% at 3 and 180% at 18 months). 3xTg-AD animals also exhibit reduced N(v) of perforated axospinous synapses (PS) in CA1 S. Mol (56% at 3 and 52% at 18 months). No changes were observed in the N(v) of symmetric and asymmetrical synapses or SERT-Ax. Our results suggest that concomitant SERT-Te N(v) increase and PS reduction in 3xTg-AD mice may act as a compensatory mechanism maintaining synaptic efficacy as a response to the AD cognitive impairment.
authors.affiliation: Faculty of Life Sciences, The University of Manchester, UK.
authors.forename: H N
authors.initials: HN
authors.lastname: Noristani
authors.forename: R S
authors.initials: RS
authors.lastname: Meadows
authors.forename: M
authors.initials: M
authors.lastname: Olabarria
authors.forename: A
authors.initials: A
authors.lastname: Verkhratsky
authors.forename: J J
authors.initials: JJ
authors.lastname: Rodríguez
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000682:Amyloid / Q000378:metabolism; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism* / Q000648:ultrastructure*; D004195:Disease Models, Animal; D051379:Mice; D008822:Mice, Transgenic; D009412:Nerve Fibers / Q000648:ultrastructure; D050486:Serotonin Plasma Membrane Transport Proteins / Q000276:immunology / Q000378:metabolism*
chemical_list: D000682:Amyloid; D050486:Serotonin Plasma Membrane Transport Proteins