Nogo-A Expression in the Human Hippocampus in Normal Aging and in Alzheimer Disease

Abstract

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.

Minocycline but not valproic acid influence the density of NogoA-immunoreactive neurons in the hilus of the dentate gyrus of the rats subjected to intracerebral haematoma

“…It is generally believed that NogoA expression in adult brain is characteristic for plastic CNS regions like cortex, dorsal root ganglia and of course hippocampus [28,30,34]. In human, increased immunoreactivity of NogoA-positive hippocampal neurons was observed in Alzheimer disease [9] and temporal lobe epilepsy [3]. The increase was also present in the experimental models of brain diseases including epilepsy [28,41] or brain injury [26,28,30].…”

NOGO is increased and binds to BACE1 in sporadic inclusion-body myositis and in AβPP-overexpressing cultured human muscle fibers

“…Nogo-B has also been reported in cell surface caveolae/lipid rafts [1]. Nogo-A has been reported to participate in several neurodegenerative disorders [reviewed in 44], and recently it was shown accumulated in the A -containing senile plaques of Alzheimer-disease brains [17].…”

“…They were then transferred to a nitrocellulose membrane and incubated with a primary antibody overnight at 4°C. The following well-characterized antibodies against Nogo were used: (a) rabbit polyclonal antibody R461, recognizing Nogo-A/B on immunoblots [18]; (b) goat polyclonal antibody N-18, also recognizing Nogo-A/B [1,17]; and (c) rabbit polyclonal antibody H-300, recognizing an epitope exclusively present on the N-terminal of Nogo-A [30]. Further, a rabbit polyclonal antibody R454, recognizing RTN3 [18], was also used in preliminary experiments.…”

The Nogo/Nogo Receptor (NgR) Signal Is Involved in Neuroinflammation through the Regulation of Microglial Inflammatory Activation

“…In AD, chronic inflammatory is not a passive system activated by emerging senile plaques and neurofibrillary tangles but instead contributes more to pathogenesis than to plaques and tangles themselves (34). Moreover, Nogo-A is overexpressed by hippocampal neurons in AD and is associated with A␤-amyloid deposits in senile plaques (35). Hence, might the potentiated effects of Nogo peptide contribute to chronic inflammatory processes and furthermore be involved in pathogenesis of chronic inflammatory diseases?…”