Early neuropathology of somatostatin/NPY GABAergic cells in the hippocampus of a PS1xAPP transgenic model of Alzheimer's disease.
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.
Ramos
Blanca
B
Department Bioquimica, Bromatologia, Toxicologia y Medicina Legal, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, Spain.
Baglietto-Vargas
David
D
del Rio
Juan Carlos
JC
Moreno-Gonzalez
Ines
I
Santa-Maria
Consuelo
C
Jimenez
Sebastian
S
Caballero
Cristina
C
Lopez-Tellez
Juan Felix
JF
Khan
Zafar U
ZU
Ruano
Diego
D
Gutierrez
Antonia
A
Vitorica
Javier
J
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
D016564:Amyloid beta-Protein Precursor; D009478:Neuropeptide Y; D012333:RNA, Messenger; D013004:Somatostatin; D005680:gamma-Aminobutyric Acid