Comparative analysis of early neurodegeneration signs in a mouse model of Alzheimer's disease-like pathology induced by two types of the central (Intracerebroventricular vs. Intrahippocampal) administration of Aß25-35 oligomers.
Behav Brain Res
; 454: 114651, 2023 10 02.
Article
em En
| MEDLINE
| ID: mdl-37657512
ABSTRACT
Animal models of Alzheimer's disease (AD) induced by intracerebroventricular (ICV) or intrahippocampal (IH) administration of amyloid-beta (Aß) are widely used in current research. It remains unclear whether these models provide similar outcomes or mimic pathological mechanisms of AD equally. The aim of the work was to compare two models induced by ICV or IH administration of Aß25-35 oligomers to C57BL/6 mice. Parameters characterizing cognitive function (passive avoidance test), protein expression (IBA1, Aß, LC3-II) and expression of genes for neuroinflammation (Aif1, Lcn2, Nrf2), autophagy (Atg8, Becn1, Park2), or markers of neurodegeneration (Cst3, Insr, Vegfa) were analyzed. Сognitive deficits, amyloid accumulation, and neuroinflammatory response in the brain evaluated by the microglial activation were similar in both models. Thus, both ways of Aß administration appear to be equally suitable for modelling AD-like pathology in mice. Our findings strongly support the key role of Aß load and neuroinflammatory response in the hippocampus and frontal cortex for the progression of AD-like pathology and development of cognitive deficits. There were certain minor differences between the models in the mRNA level of genes involved in the processes of neuroinflammation, neurodegeneration, and autophagy. Modulating effects of the central administration of Aß25-35 on the mRNA expression of Aif1, Lcn2, Park2, and Vegfa genes in different brain structures were revealed. The effects occurred to be more pronounced with the ICV method compared with the IH method. These findings give insight into the processes at initial stages of Aß-induced pathology depending on a primary location of Aß oligomers in the brain.
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Alzheimer
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article