To determine the stability of β-amyloid peptide (Aβ) and the glial and neuronal changes induced by Aβ in the CNS in vivo, we made single injections of fibrillar Aβ (fAβ), soluble Aβ (sAβ), or vehicle into the rat striatum. Injected fAβ is stable in vivo for at least 30 d after injection, whereas sAβ is primarily cleared within 1 d. After injection of fAβ microgila phagocyfize fAβ aggregates, whereas nearby astrocytes form a virtual wall between fAβ-containing microgila and the surrounding neuropil. Similar glial changes are not observed after sAβ injection. Microgila and astrocytes near the injected tAβ show a significant increase in inducible nitric oxide synthase (iNOS) expression compared with that seen with sAβ or vehicle injection. Injection of fAβ but not sAβ or vehicle induces a significant loss of parvalbuminand neuronal nitric oxide synthase- immunoreactive neurons, whereas the number of calbindin-immunoreactive neurons remains unchanged. These data demonstrate that fAβ is remarkably stable in the CNS in vivo and suggest that fAβ neurotoxicity is mediated in large part by factors released from activated microglia and astrocytes, as opposed to direct interaction between Aβ fibrils and neurons.
|Original language||English (US)|
|Number of pages||13|
|Journal||Journal of Neuroscience|
|State||Published - Mar 15 1998|
- Alzheimer's disease
- Inducible nitric oxide synthase
- Nitric oxide synthase