Neuroinflammation impairs adaptive structural plasticity of dendritic spines in a preclinical model of Alzheimer’s disease

• DOI: 10.1007/s00401-015-1527-8
• Publication Date: 2016-01-02T02:55:02Z
• Authors: Chengyu Zou; Yuan Shi; Jasmin Ohli; Ulrich Schüller; Mario M. Dorostkar; Jochen Herms
• Keywords: drug effects [Pyramidal Cells]; Anti-Inflammatory Agents; genetics [Amyloid Precursor Protein Secretases]; immunology [Dendritic Spines]; drug effects [Neuroimmunomodulation]; pathology [Alzheimer Disease]; drug effects [Somatosensory Cortex]; drug effects [Neuronal Plasticity]; drug therapy [Alzheimer Disease]; Aspartic Acid Endopeptidases; immunology [Pyramidal Cells]; 0303 health sciences; Neuronal Plasticity; Pyramidal Cells; metabolism [Aspartic Acid Endopeptidases]; 3. Good health; pathology [Pyramidal Cells]; Female; Neuroimmunomodulation; Bace1 protein, mouse; Dendritic Spines; Clinical Neurology; Mice, Transgenic; pharmacology [Thiazolidinediones]; immunology [Neuroimmunomodulation]; Pathology and Forensic Medicine; Cellular and Molecular Neuroscience; 03 medical and health sciences; Alzheimer Disease; Animals; ddc:610; drug effects [Dendritic Spines]; Receptors, Interleukin-1 Type I; Original Paper; Pioglitazone; Somatosensory Cortex; pathology [Somatosensory Cortex]; pharmacology [Anti-Inflammatory Agents]; metabolism [Amyloid Precursor Protein Secretases]; immunology [Neuronal Plasticity]; immunology [Somatosensory Cortex]; immunology [Alzheimer Disease]; Mice, Inbred C57BL; Disease Models, Animal; genetics [Aspartic Acid Endopeptidases]; metabolism [Receptors, Interleukin-1 Type I]; antagonists & inhibitors [Receptors, Interleukin-1 Type I]; Thiazolidinediones; Amyloid Precursor Protein Secretases; pathology [Dendritic Spines]

To successfully treat Alzheimer's disease (AD), pathophysiological events in preclinical stages need to be identified. Preclinical AD refers the that exhibit amyloid deposition brain but have normal cognitive function, which are replicated young adult APPswe/PS1deltaE9 (deltaE9) mice. By long-term vivo two-photon microscopy, we demonstrate impaired adaptive spine plasticity these transgenic mice illustrated by their failure increase dendritic density and form novel neural connections when housed enriched environment (EE). Decrease of plaques reducing BACE1 activity restores gain upon EE deltaE9 mice, not remodeling networks. On other hand, anti-inflammatory treatment with pioglitazone or interleukin 1 receptor antagonist rescues impairments increasing networks during EE. Our data suggest neuroinflammation disrupts experience-dependent structural spines AD.