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Immunization with either prion protein fragment 95-123 or the fragment-specific antibodies rescue memory loss and neurodegenerative phenotype of neurons in olfactory bulbectomized mice.

Abstract：

:Epidemiological studies demonstrated association between head injury (HI) and the subsequent development of Alzheimer's disease (AD). Certain hallmarks of AD, e.g. amyloid-β (Aβ) containing deposits, may be found in patients following traumatic BI (TBI). Recent studies uncover the cellular prion protein, PrP(C), as a receptor for soluble polymeric forms of Aβ (sAβ) which are an intermediate of such deposits. We aimed to test the hypothesis that targeting of PrP(C) can prevent Aβ related spatial memory deficits in olfactory bulbectomized (OBX) mice utilized here to resemble some clinical features of AD, such as increased level of Aβ, memory loss and deficit of the CNS cholin- and serotonin-ergic systems. We demonstrated that immunization with the a.a. 95-123 fragment of cellular prion (PrP-I) recovered cortical and hippocampus neurons from OBX induced degeneration, rescued spatial memory loss in Morris water maze test and significantly decrease the Aβ level in brain tissue of these animals. Affinity purified anti-PrP-I antibodies rescued pre-synaptic biomarker synaptophysin eliciting similar effect on memory of OBX mice, and protected hippocampal neurones from Aβ25-35-induced toxicity in vitro. Immunization OBX mice with a.a. 200-213 fragment of cellular prion (PrP-II) did not reach a significance in memory protection albeit having similar to PrP-I immunization impact on Aβ level in brain tissue. The observed positive effect of targeting the PrP-I by either active or passive immunization on memory of OBX mice revealed the involvement of the PrP(C) in AD-like pathology induced by olfactory bulbectomy. This OBX model may be a useful tool for mechanistic and preclinical therapeutic investigations into the association between PrP(C) and AD.

journal_name

Neurobiol Learn Mem

journal_title

Neurobiology of learning and memory

authors

Bobkova NV,Medvinskaya NI,Kamynina AV,Aleksandrova IY,Nesterova IV,Samokhin AN,Koroev DO,Filatova MP,Nekrasov PV,Abramov AY,Leonov SV,Volpina OM

doi

10.1016/j.nlm.2013.10.019

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

50-64

eissn

1074-7427

issn

1095-9564

pii

S1074-7427(13)00214-1

journal_volume

107

pub_type

杂志文章

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Immunization with either prion protein fragment 95-123 or the fragment-specific antibodies rescue memory loss and neurodegenerative phenotype of neurons in olfactory bulbectomized mice.