Amyloid β peptide adversely affects spine number and motility in hippocampal neurons

Brikha R. Shrestha, Ottavio V. Vitolo, Powrnima Joshi, Tamar Lordkipanidze, Michael Shelanski, Anna Dunaevsky-Hutt

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

Elevated levels of amyloid-beta peptide (Aβ) 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 Aβ on the development of dendritic spines. We report that exposure of hippocampal neurons to sub-lethal levels of Aβ decreased spine density, increased spine length and subdued spine motility. The effect of Aβ on spine density was reversible. Moreover, Aβ'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 Aβ-induced spine alterations could underlie the cognitive defects in Alzheimer's disease and Down syndrome.

Original languageEnglish (US)
Pages (from-to)274-282
Number of pages9
JournalMolecular and Cellular Neuroscience
Volume33
Issue number3
DOIs
StatePublished - Nov 6 2006

Fingerprint

Amyloid
Spine
Dendritic Spines
Neurons
Peptides
Alzheimer Disease
Down Syndrome
Type 4 Cyclic Nucleotide Phosphodiesterase
Rolipram
Neuronal Plasticity
Phosphodiesterase Inhibitors
Pyramidal Cells
Amyloid beta-Peptides
Photons

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

Amyloid β peptide adversely affects spine number and motility in hippocampal neurons. / Shrestha, Brikha R.; Vitolo, Ottavio V.; Joshi, Powrnima; Lordkipanidze, Tamar; Shelanski, Michael; Dunaevsky-Hutt, Anna.

In: Molecular and Cellular Neuroscience, Vol. 33, No. 3, 06.11.2006, p. 274-282.

Research output: Contribution to journalArticle

Shrestha, Brikha R. ; Vitolo, Ottavio V. ; Joshi, Powrnima ; Lordkipanidze, Tamar ; Shelanski, Michael ; Dunaevsky-Hutt, Anna. / Amyloid β peptide adversely affects spine number and motility in hippocampal neurons. In: Molecular and Cellular Neuroscience. 2006 ; Vol. 33, No. 3. pp. 274-282.
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