title: Early neuropathology of somatostatin/NPY GABAergic cells in the hippocampus of a PS1xAPP transgenic model of Alzheimer's disease.
abstract: At advanced stages, Alzheimer's disease (AD) is characterized by an extensive neuronal loss. However, the early neurodegenerative deficiencies have not been yet identified. Here we report an extensive, selective and early neurodegeneration of the dendritic inhibitory interneurons (oriens-lacunosum moleculare, O-LM, and hilar perforant path-associated, HIPP, cells) in the hippocampus of a transgenic PS1xAPP AD model. At 6 months of age, from 22 different pre- and postsynaptic mRNA markers tested (including GABAergic, glutamatergic and cholinergic markers), only the expression of somatostatin (SOM) and NPY neuropeptides (O-LM and HIPP markers) displayed a significant decrease. Stereological cell counting demonstrated a profound diminution (50-60%) of SOM-immunopositive neurons, preceding the pyramidal cell loss in this AD model. SOM population co-expressing NPY was the most damaged cell subset. Furthermore, a linear correlation between SOM and/or NPY deficiency and Abeta content was also observed. Though the molecular mechanism of SOM neuronal loss remains to be determined, these findings might represent an early hippocampal neuropathology. Therefore, SOM and NPY neuropeptides could constitute important biomarkers to assess the efficacy of potential early AD treatments.
authors.affiliation: Department Bioquimica, Bromatologia, Toxicologia y Medicina Legal, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, Spain.
authors.forename: Blanca
authors.initials: B
authors.lastname: Ramos
authors.forename: David
authors.initials: D
authors.lastname: Baglietto-Vargas
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: del Rio
authors.forename: Ines
authors.initials: I
authors.lastname: Moreno-Gonzalez
authors.forename: Consuelo
authors.initials: C
authors.lastname: Santa-Maria
authors.forename: Sebastian
authors.initials: S
authors.lastname: Jimenez
authors.forename: Cristina
authors.initials: C
authors.lastname: Caballero
authors.forename: Juan Felix
authors.initials: JF
authors.lastname: Lopez-Tellez
authors.forename: Zafar U
authors.initials: ZU
authors.lastname: Khan
authors.forename: Diego
authors.initials: D
authors.lastname: Ruano
authors.forename: Antonia
authors.initials: A
authors.lastname: Gutierrez
authors.forename: Javier
authors.initials: J
authors.lastname: Vitorica
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D007395:Interneurons / Q000166:cytology*; D051379:Mice; D008822:Mice, Transgenic; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013004:Somatostatin / Q000235:genetics / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D009478:Neuropeptide Y; D012333:RNA, Messenger; D013004:Somatostatin; D005680:gamma-Aminobutyric Acid