Early inflammation and immune response mRNAs in the brain of AD11 anti-NGF mice.
We characterized the gene expression profile of brain regions at an early stage of the Alzheimer's like neurodegeneration in the anti-NGF AD11 model. Total RNA was extracted from hippocampus, cortex and basal forebrain of postnatal day 30 (P30) and postnatal day 90 (P90) mice and expression profiles were studied by microarray analysis, followed by qRT-PCR validation of 243 significant candidates. Wide changes in gene expression profiles occur already at P30. As expected, cholinergic system and neurotrophins related genes expression were altered. Interestingly, the most significantly affected clusters of mRNAs are linked to inflammation and immune response, as well as to Wnt signaling. mRNAs encoding for different complement factors show a large differential expression. This is noteworthy, since these complement cascade proteins are involved in CNS synapse elimination, during normal brain developing and in neurodegenerative diseases. This gene expression pattern highlights that an early event in AD11 neurodegeneration is represented, together with neurotrophic deficits and synaptic remodeling, by an inflammatory response and an unbalance in the immunotrophic state of the brain. These might be key events in the pathogenesis and development of AD.
D'Onofrio
Mara
M
European Brain Research Institute Rita Levi-Montalcini, Via del Fosso di Fiorano 64, 00143 Roma, Italy.
Arisi
Ivan
I
Brandi
Rossella
R
Di Mambro
Alessandra
A
Felsani
Armando
A
Capsoni
Simona
S
Cattaneo
Antonino
A
D000367:Age Factors; D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000235:genetics / Q000378:metabolism; D001921:Brain / Q000276:immunology / Q000378:metabolism*; D002795:Choline O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D007249:Inflammation / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D020932:Nerve Growth Factor / Q000276:immunology; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000209:etiology / Q000235:genetics / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012333:RNA, Messenger / Q000276:immunology / Q000378:metabolism*; D011950:Receptors, Cholinergic / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D018709:Statistics, Nonparametric; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism
D000906:Antibodies; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D011950:Receptors, Cholinergic; D051153:Wnt Proteins; D020932:Nerve Growth Factor; D002795:Choline O-Acetyltransferase