Neuroinflammation impairs adaptive structural plasticity of dendritic spines in a preclinical model of Alzheimer's disease
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Neuroinflammation impairs adaptive structural plasticity of dendritic spines in a preclinical model of Alzheimer's disease. / Zou, Chengyu; Shi, Yuan; Ohli, Jasmin; Schüller, Ulrich; Dorostkar, Mario M; Herms, Jochen.
In: ACTA NEUROPATHOL, Vol. 131, No. 2, 02.2016, p. 235-246.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Neuroinflammation impairs adaptive structural plasticity of dendritic spines in a preclinical model of Alzheimer's disease
AU - Zou, Chengyu
AU - Shi, Yuan
AU - Ohli, Jasmin
AU - Schüller, Ulrich
AU - Dorostkar, Mario M
AU - Herms, Jochen
PY - 2016/2
Y1 - 2016/2
N2 - To successfully treat Alzheimer's disease (AD), pathophysiological events in preclinical stages need to be identified. Preclinical AD refers to the stages that exhibit amyloid deposition in the brain but have normal cognitive function, which are replicated in young adult APPswe/PS1deltaE9 (deltaE9) mice. By long-term in vivo two-photon microscopy, we demonstrate impaired adaptive spine plasticity in these transgenic mice illustrated by their failure to increase dendritic spine density and form novel neural connections when housed in enriched environment (EE). Decrease of amyloid plaques by reducing BACE1 activity restores the gain of spine density upon EE in deltaE9 mice, but not the remodeling of neural networks. On the other hand, anti-inflammatory treatment with pioglitazone or interleukin 1 receptor antagonist in deltaE9 mice successfully rescues the impairments in increasing spine density and remodeling of neural networks during EE. Our data suggest that neuroinflammation disrupts experience-dependent structural plasticity of dendritic spines in preclinical stages of AD.
AB - To successfully treat Alzheimer's disease (AD), pathophysiological events in preclinical stages need to be identified. Preclinical AD refers to the stages that exhibit amyloid deposition in the brain but have normal cognitive function, which are replicated in young adult APPswe/PS1deltaE9 (deltaE9) mice. By long-term in vivo two-photon microscopy, we demonstrate impaired adaptive spine plasticity in these transgenic mice illustrated by their failure to increase dendritic spine density and form novel neural connections when housed in enriched environment (EE). Decrease of amyloid plaques by reducing BACE1 activity restores the gain of spine density upon EE in deltaE9 mice, but not the remodeling of neural networks. On the other hand, anti-inflammatory treatment with pioglitazone or interleukin 1 receptor antagonist in deltaE9 mice successfully rescues the impairments in increasing spine density and remodeling of neural networks during EE. Our data suggest that neuroinflammation disrupts experience-dependent structural plasticity of dendritic spines in preclinical stages of AD.
KW - Alzheimer Disease
KW - Amyloid Precursor Protein Secretases
KW - Animals
KW - Anti-Inflammatory Agents
KW - Aspartic Acid Endopeptidases
KW - Dendritic Spines
KW - Disease Models, Animal
KW - Female
KW - Mice, Inbred C57BL
KW - Mice, Transgenic
KW - Neuroimmunomodulation
KW - Neuronal Plasticity
KW - Pyramidal Cells
KW - Receptors, Interleukin-1 Type I
KW - Somatosensory Cortex
KW - Thiazolidinediones
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1007/s00401-015-1527-8
DO - 10.1007/s00401-015-1527-8
M3 - SCORING: Journal article
C2 - 26724934
VL - 131
SP - 235
EP - 246
JO - ACTA NEUROPATHOL
JF - ACTA NEUROPATHOL
SN - 0001-6322
IS - 2
ER -
