Nogo-A expression in the human hippocampus in normal aging and in Alzheimer disease.
Myelin-associated proteins are involved in the formation and stabilization of myelin sheaths. In addition, they prevent axon regeneration and plasticity in the adult brain. Recent evidence suggests that the expression of certain myelin-associated proteins (e.g. Nogo-A) can be regulated by synaptic activity or by over-expression after neural lesions in brain syndromes such as temporal lobe epilepsy. However, no studies on Alzheimer disease (AD) have been reported in which cell loss and significant synaptic reorganization occurs. In the present study, we analyze in detail the expression of Nogo-A in the hippocampal formation in normal human aging and in AD. Our results indicate that Nogo-A is expressed by oligodendrocytes and neurons in the aged hippocampal formation. In addition, both granule cells and mossy fiber connections are also labeled in the old-aged hippocampi. Interestingly, Nogo-A is over-expressed by hippocampal neurons in AD and is associated with beta-amyloid deposits in senile plaques. Taken together, our results reinforce the hypothesis that Reticulon proteins such as Nogo-A participate in the neuronal responses stemming from hippocampal formation during senescence, and particularly in AD. These findings also indicate that Reticulon proteins could be considered as new putative drug targets in therapies of neurodegenerative disorders.
Gil
Vanessa
V
Development and Regeneration of the CNS, IRB-PCB, Barcelona Science Park, University of Barcelona, Spain.
Nicolas
Oriol
O
Mingorance
Ana
A
Ureña
Jesús Mariano
JM
Tang
Bor Lueng
BL
Hirata
Tatsumi
T
Sáez-Valero
Javier
J
Ferrer
Isidro
I
Soriano
Eduardo
E
del Río
José Antonio
JA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000906:Antibodies / Q000378:metabolism; D015153:Blotting, Western / Q000379:methods; D005260:Female; D015870:Gene Expression / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D047468:Immunoprecipitation / Q000379:methods; D008297:Male; D008875:Middle Aged; D004676:Myelin Basic Protein / Q000378:metabolism; D009185:Myelin Proteins / Q000276:immunology / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D000070798:Nogo Proteins; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011180:Postmortem Changes; D051603:Recoverin / Q000378:metabolism
D016229:Amyloid beta-Peptides; D000906:Antibodies; D005904:Glial Fibrillary Acidic Protein; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D000070798:Nogo Proteins; C496731:RCVRN protein, human; C000603199:RTN4 protein, human; D051603:Recoverin; D010751:Phosphopyruvate Hydratase