Dataset Information

Treatment of beta amyloid 1-42 (A?(1-42))-induced basal forebrain cholinergic damage by a non-classical estrogen signaling activator in vivo.

ABSTRACT: In Alzheimer's disease (AD), there is a loss in cholinergic innervation targets of basal forebrain which has been implicated in substantial cognitive decline. Amyloid beta peptide (A?(1-42)) accumulates in AD that is highly toxic for basal forebrain cholinergic (BFC) neurons. Although the gonadal steroid estradiol is neuroprotective, the administration is associated with risk of off-target effects. Previous findings suggested that non-classical estradiol action on intracellular signaling pathways has ameliorative potential without estrogenic side effects. After A?(1-42) injection into mouse basal forebrain, a single dose of 4-estren-3?, 17?-diol (estren), the non-classical estradiol pathway activator, restored loss of cholinergic cortical projections and also attenuated the A?(1-42)-induced learning deficits. Estren rapidly and directly phosphorylates c-AMP-response-element-binding-protein and extracellular-signal-regulated-kinase-1/2 in BFC neurons and restores the cholinergic fibers via estrogen receptor-?. These findings indicated that selective activation of non-classical intracellular estrogen signaling has a potential to treat the damage of cholinergic neurons in AD.

SUBMITTER: Kwakowsky A

PROVIDER: S-EPMC4754683 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Treatment of beta amyloid 1-42 (Aβ(1-42))-induced basal forebrain cholinergic damage by a non-classical estrogen signaling activator in vivo.

Kwakowsky Andrea A Potapov Kyoko K Kim SooHyun S Peppercorn Katie K Tate Warren P WP Ábrahám István M IM

Scientific reports 20160216

In Alzheimer's disease (AD), there is a loss in cholinergic innervation targets of basal forebrain which has been implicated in substantial cognitive decline. Amyloid beta peptide (Aβ(1-42)) accumulates in AD that is highly toxic for basal forebrain cholinergic (BFC) neurons. Although the gonadal steroid estradiol is neuroprotective, the administration is associated with risk of off-target effects. Previous findings suggested that non-classical estradiol action on intracellular signaling pathway ...[more]

PMID: 26879842

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Project description:BackgroundGait disturbance is an early, disabling feature of Parkinson's disease (PD) that is typically refractory to dopaminergic medication. The cortical cholinergic system, originating in the nucleus basalis of Meynert of the basal forebrain, has been implicated. However, it is not known if degeneration in this region relates to a worsening of disease-specific gait impairment.ObjectiveTo evaluate associations between sub-regional cholinergic basal forebrain volumes and longitudinal progression of gait impairment in PD.Methods99 PD participants and 47 control participants completed gait assessments via an instrumented walkway during 2 minutes of continuous walking, at baseline and for up to 3 years, from which 16 spatiotemporal characteristics were derived. Sub-regional cholinergic basal forebrain volumes were measured at baseline via MRI and a regional map derived from post-mortem histology. Univariate analyses evaluated cross-sectional associations between sub-regional volumes and gait. Linear mixed-effects models assessed whether volumes predicted longitudinal gait changes.ResultsThere were no cross-sectional, age-independent relationships between sub-regional volumes and gait. However, nucleus basalis of Meynert volumes predicted longitudinal gait changes unique to PD. Specifically, smaller nucleus basalis of Meynert volume predicted increasing step time variability (P = 0.019) and shortening swing time (P = 0.015); smaller posterior nucleus portions predicted shortening step length (P = 0.007) and increasing step time variability (P = 0.041).ConclusionsThis is the first study to demonstrate that degeneration of the cortical cholinergic system predicts longitudinal progression of gait impairments in PD. Measures of this degeneration may therefore provide a novel biomarker for identifying future mobility loss and falls. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Dataset Information

Treatment of beta amyloid 1-42 (A?(1-42))-induced basal forebrain cholinergic damage by a non-classical estrogen signaling activator in vivo.

Publications

Treatment of beta amyloid 1-42 (Aβ(1-42))-induced basal forebrain cholinergic damage by a non-classical estrogen signaling activator in vivo.

Similar Datasets

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