Amyloid beta peptide adversely affects spine number and motility in hippocampal neurons.
Elevated levels of amyloid-beta peptide (Abeta) are found in Down's syndrome patients and alter synaptic function during the early stages of Alzheimer's disease. Dendritic spines, sites of most excitatory synaptic contacts, are considered to be an important locus for encoding synaptic plasticity. We used time-lapse two-photon imaging of hippocampal pyramidal neurons in organotypic slices to study the effects of Abeta on the development of dendritic spines. We report that exposure of hippocampal neurons to sub-lethal levels of Abeta decreased spine density, increased spine length and subdued spine motility. The effect of Abeta on spine density was reversible. Moreover, Abeta's effect on dendritic spine density was blocked by rolipram, a phosphodiesterase type IV inhibitor, suggesting the involvement of a cAMP dependent pathway. These findings raise the possibility that Abeta-induced spine alterations could underlie the cognitive defects in Alzheimer's disease and Down syndrome.
Shrestha
Brikha R
BR
Department of Neuroscience, Brown University, Box 1953, 190 Thayer Street, Providence, RI 02912, USA.
Vitolo
Ottavio V
OV
Joshi
Powrnima
P
Lordkipanidze
Tamar
T
Shelanski
Michael
M
Dunaevsky
Anna
A
D016229:Amyloid beta-Peptides / Q000009:adverse effects*; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western / Q000379:methods; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D000242:Cyclic AMP / Q000502:physiology; D049229:Dendritic Spines / Q000187:drug effects* / Q000648:ultrastructure; D003952:Diagnostic Imaging / Q000379:methods; D005455:Fluorescent Antibody Technique / Q000379:methods; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D051379:Mice; D008855:Microscopy, Electron, Scanning / Q000379:methods; D010446:Peptide Fragments / Q000009:adverse effects*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D017966:Pyramidal Cells / Q000166:cytology / Q000187:drug effects*; D020889:Rolipram / Q000494:pharmacology; D018709:Statistics, Nonparametric; D013997:Time Factors; D014162:Transfection / Q000379:methods
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D010726:Phosphodiesterase Inhibitors; C075222:amyloid beta-protein (1-42); D049452:Green Fluorescent Proteins; D000242:Cyclic AMP; D020889:Rolipram