Chauhan NB (2006) Cholinergic immunolesioning produced tangle-like inclusions in TgCRND8 brain. Neuroscience 2006 Abstracts 271.8. Society for Neuroscience, Atlanta, GA.
Summary: Today’s Alzheimer’s disease (AD) research lacks a “complete” model that would represent both plaque and tangle pathology together with correlative memory deficits. Although currently developed transgenic model including APP/PS1/tau mutations do not “truly” represent AD because tangles observed in AD brain are independent of tau mutations. Subtly increased β-amyloid (Aβ) levels either due to familial mutations or sporadic causes, primarily targets pre-tangle cytopathology and degeneration of basal forebrain cholinergic neurons (BFCN) via deranged signaling of glygogen synthase kinase 3-beta (GSK3β)-, protein kinase A (PKA)-, and extracellular signal-regulated kinase (ERK2) of ERK-mitogen-activated protein kinase (MAPK) cascade, leading to reduced phosphorylation of cAMP responsive element binding protein (CREB) that results in synaptic and memory deficits much earlier than the emergence of classic AD-pathology. Thus, subtly elevated Aβ, together with BFCN deficits resulting from Aβ-induced deranged signaling, set up a vicious feedback loop to produce characteristic plaque- and tangle-pathology observed in AD. Based on these facts, we wished to test if selective lesioning of basal fore brain cholinergic neurons during the early stages of amyloid build-up will exacerbate tau phosphorylation and produce tangle-like inclusions in transgenic mice with APP mutations. We produced selective immunotoxic lesions of BFCN by injecting the BFCN-specific cholinergic immunotoxin, which is known to specifically target p75-expressing BFCN and spare p75-expressing cerebellar neurons (Mu-p75-Saporin, Advanced Targeting Systems, #IT-16), intracerebroventricularly (ICV) in TgCRND8 mice harboring Swedish (KM670/671NL) and Indiana (V717F) mutations. This model exhibited tangle-like inclusions, provoked already existing plaque pathology, and worsened already impaired behavioral deficits.
Related Products: mu p75-SAP (Cat. #IT-16)
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