Article

Time-Course and Regional Analyses of the Physiopathological Changes Induced after Cerebral Injection of an Amyloid β Fragment in Rats

Molecular Mechanisms in Neurodegenerative Dementia Laboratory, Inserm U710, Montpellier, France.
American Journal Of Pathology (Impact Factor: 4.6). 07/2011; 179(1):315-34. DOI: 10.1016/j.ajpath.2011.03.021
Source: PubMed

ABSTRACT Alzheimer's disease (AD) is a neurodegenerative pathology characterized by the presence of senile plaques and neurofibrillary tangles, accompanied by synaptic and neuronal loss. The major component of senile plaques is an amyloid β protein (Aβ) formed by pathological processing of the Aβ precursor protein. We assessed the time-course and regional effects of a single intracerebroventricular injection of aggregated Aβ fragment 25-35 (Aβ(25-35)) in rats. Using a combined biochemical, behavioral, and morphological approach, we analyzed the peptide effects after 1, 2, and 3 weeks in the hippocampus, cortex, amygdala, and hypothalamus. The scrambled Aβ(25-35) peptide was used as negative control. The aggregated forms of Aβ peptides were first characterized using electron microscopy, infrared spectroscopy, and Congo Red staining. Intracerebroventricular injection of Aβ(25-35) decreased body weight, induced short- and long-term memory impairments, increased endocrine stress, cerebral oxidative and cellular stress, neuroinflammation, and neuroprotective reactions, and modified endogenous amyloid processing, with specific time-course and regional responses. Moreover, Aβ(25-35), the presence of which was shown in the different brain structures and over 3 weeks, provoked a rapid glial activation, acetylcholine homeostasis perturbation, and hippocampal morphological alterations. In conclusion, the acute intracerebroventricular Aβ(25-35) injection induced substantial central modifications in rats, highly reminiscent of the human physiopathology, that could contribute to physiological and cognitive deficits observed in AD.

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Questions & Answers about this publication

  • Florian Duclot added an answer in Transgenic Rats:
    What are the best non-transgenic Alzheimer's disease rat models?

    I'm trying to study about non-transgenic rat models in alzheimer's disease and the information about non-transgenic rat model is less than transgenic rat model. 

    Florian Duclot · Florida State University

    If you're looking at a non-transgenic rat model of AD, have a look at the following publication (see end of message). As someone previously explained, modeling all aspects of the human pathology is complex and difficult, but this model incudes a wide range of AD-like symptoms (behavioral and molecular). Have a look at other publications from this group for more information.

    Hope this helps.