Sustained Hippocampal Neural Plasticity Questions the Reproducibility of an Amyloid-β-Induced Alzheimer's Disease Model

被引：2

作者：

Paulo, Sara L. ^{[1
,2
]}

Ribeiro-Rodrigues, Leonor ^{[1
,2
]}

Rodrigues, Rui S. ^{[1
,2
]}

Mateus, Joana M. ^{[1
,2
]}

Fonseca-Gomes, Joao ^{[1
,2
]}

Soares, Rita ^{[1
,2
,3
]}

Diogenes, Maria J. ^{[1
,2
]}

Sola, Susana ^{[4
]}

Sebastiao, Ana M. ^{[1
,2
]}

Ribeiro, Filipa F. ^{[1
,2
]}

Xapelli, Sara ^{[1
,2
]}

机构：

[1] Univ Lisbon, Fac Med, Inst Farmacol & Neurociencias, P-1649028 Lisbon, Portugal

[2] Univ Lisbon, Fac Med, Inst Med Mol Joao Lobo Antunes, Lisbon, Portugal

[3] Univ Lisbon, Fac Med, Inst Biol Mol, Lisbon, Portugal

[4] Univ Lisbon, Fac Farm, Res Inst Med iMed ULisboa, Lisbon, Portugal

来源：

JOURNAL OF ALZHEIMERS DISEASE | 2021年 / 82卷 / 03期

基金：

欧盟地平线“2020”;

关键词：

Alzheimer's disease; amyloid-beta peptide; behavior; hippocampal plasticity; memory; TRANSGENIC MOUSE MODELS; A-BETA; INTRACEREBROVENTRICULAR INJECTION; AMYLOID-BETA(1-42) PEPTIDE; ADULT NEUROGENESIS; CASCADE HYPOTHESIS; DENTATE GYRUS; MEMORY; NEURONS; DYSFUNCTION;

D O I：

10.3233/JAD-201567

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Background: The use of Alzheimer's disease (AD) models obtained by intracerebral infusion of amyloid-beta (A beta) has been increasingly reported in recent years. Nonetheless, these models may present important challenges. Objective: We have focused on canonical mechanisms of hippocampal-related neural plasticity to characterize a rat model obtained by an intracerebroventricular (icv) injection of soluble amyloid-C-42 (A beta(42)). Methods: Animal behavior was evaluated in the elevated plus maze, Y-Maze spontaneous or forced alternation, Morris water maze, and open field, starting 2 weeks post-A beta(42) infusion. Hippocampal neurogenesis was assessed 3 weeks after A beta(42) injection. A beta deposition, tropomyosin receptor kinase B levels, and neuroinflammation were appraised at 3 and 14 days post-A beta(42) administration. Results: We found that immature neuronal dendritic morphology was abnormally enhanced, but proliferation and neuronal differentiation in the dentate gyrus was conserved one month after A beta(42) injection. Surprisingly, animal behavior did not reveal changes in cognitive performance nor in locomotor and anxious-related activity. Brain-derived neurotrophic factor related-signaling was also unchanged at 3 and 14 days post-A beta icv injection. Likewise, astrocytic and microglial markers of neuroinflammation in the hippocampus were unaltered in these time points. Conclusion: Taken together, our data emphasize a high variability and lack of behavioral reproducibility associated with these A beta injection-based models, as well as the need for its further optimization, aiming at addressing the gap between preclinical AD models and the human disorder.

引用

页码：1183 / 1202

页数：20