ParkinsonCanadaV1, Main, Exploration, bibRecord, 000663

Laminar Specific Detection of APP induced Neurodegeneration and Recovery using MEMRI in an Olfactory based Alzheimer’s Disease Mouse Model

Identifieur interne : 000663 ( Main/Exploration ); précédent : 000662; suivant : 000664

Laminar Specific Detection of APP induced Neurodegeneration and Recovery using MEMRI in an Olfactory based Alzheimer’s Disease Mouse Model

Auteurs : Galit Saar [États-Unis] ; Ning Cheng [États-Unis, Canada] ; Leonardo Belluscio [États-Unis] ; Alan P. Koretsky [États-Unis]

Source :

NeuroImage [ 1053-8119 ] ; 2015.

RBID : PMC:4732579

Abstract

Manganese Enhanced MRI (MEMRI) was used to detect specific laminar changes in the olfactory bulb (OB) to follow the progression of amyloid precursor protein (APP)-induced neuronal pathology and its recovery in a reversible olfactory based Alzheimer’s disease (AD) mouse model. Olfactory dysfunction is an early symptom of AD, which suggests that olfactory sensory neurons (OSNs) may be more sensitive to AD related factors than neurons in other brain areas. Previously a transgenic mouse model was established that causes degeneration of OSNs by overexpressing humanized APP (hAPP), which results in a disruption of olfactory circuitry with changes in glomerular structure. In the present work, OB volume and manganese enhancement of the glomerular layer in OB were decreased in mutant mice. Turning off APP overexpression with doxycycline produced a significant increase in manganese enhancement of the glomerular layer after only 1 week, and further recovery after 3 weeks, while treatment with Aβ antibody produced modest improvement with MRI measurements. Thus, MEMRI enables a direct tracking of laminar specific neurodegeneration through a non-invasive in vivo measurement. The use of MRI will enable assessment of the ability of different pharmacological reagents to block olfactory neuronal loss and can serve as a unique in vivo screening tool to both identify potential therapeutics and test their efficacy.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4732579

DOI: 10.1016/j.neuroimage.2015.05.045
PubMed: 26021215
PubMed Central: 4732579

Affiliations:

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<front><div type="abstract" xml:lang="en"><p id="P2">Manganese Enhanced MRI (MEMRI) was used to detect specific laminar changes in the olfactory bulb (OB) to follow the progression of amyloid precursor protein (APP)-induced neuronal pathology and its recovery in a reversible olfactory based Alzheimer’s disease (AD) mouse model. Olfactory dysfunction is an early symptom of AD, which suggests that olfactory sensory neurons (OSNs) may be more sensitive to AD related factors than neurons in other brain areas. Previously a transgenic mouse model was established that causes degeneration of OSNs by overexpressing humanized APP (hAPP), which results in a disruption of olfactory circuitry with changes in glomerular structure. In the present work, OB volume and manganese enhancement of the glomerular layer in OB were decreased in mutant mice. Turning off APP overexpression with doxycycline produced a significant increase in manganese enhancement of the glomerular layer after only 1 week, and further recovery after 3 weeks, while treatment with Aβ antibody produced modest improvement with MRI measurements. Thus, MEMRI enables a direct tracking of laminar specific neurodegeneration through a non-invasive <italic>in vivo</italic>
 measurement. The use of MRI will enable assessment of the ability of different pharmacological reagents to block olfactory neuronal loss and can serve as a unique <italic>in vivo</italic>
 screening tool to both identify potential therapeutics and test their efficacy.</p>
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La maladie de Parkinson au Canada (serveur d'exploration)

Laminar Specific Detection of APP induced Neurodegeneration and Recovery using MEMRI in an Olfactory based Alzheimer’s Disease Mouse Model

Laminar Specific Detection of APP induced Neurodegeneration and Recovery using MEMRI in an Olfactory based Alzheimer’s Disease Mouse Model

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Abstract

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