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Estrogen Enhances Dendrite Spine Function and Recovers Deficits in Neuroplasticity in the prpTDP-43A315T Mouse Model of Amyotrophic Lateral Sclerosis

journal contribution
posted on 2023-05-21, 17:24 authored by Handley, EE, Laura RealeLaura Reale, Jyoti ChuckowreeJyoti Chuckowree, Marcus Dyer, Barnett, GL, Courtney Clark, William BennettWilliam Bennett, Tracey DicksonTracey Dickson, Catherine BlizzardCatherine Blizzard
Amyotrophic lateral sclerosis (ALS) attacks the corticomotor system, with motor cortex function affected early in disease. Younger females have a lower relative risk of succumbing to ALS than males and older females, implicating a role for female sex hormones in disease progression. However, the mechanisms driving this dimorphic incidence are still largely unknown. We endeavoured to determine if estrogen mitigates disease progression and pathogenesis, focussing upon the dendritic spine as a site of action. Using two-photon live imaging we identify, in the prpTDP-43A315T mouse model of ALS, that dendritic spines in the male motor cortex have a reduced capacity for remodelling than their wild-type controls. In contrast, females show higher capacity for remodelling, with peak plasticity corresponding to highest estrogen levels during the estrous cycle. Estrogen manipulation through ovariectomies and estrogen replacement with 17β estradiol in vivo was found to significantly alter spine density and mitigate disease severity. Collectively, these findings reveal that synpatic plasticity is reduced in ALS, which can be amelioriated with estrogen, in conjuction with improved disease outcomes.


Publication title

Molecular Neurobiology










Menzies Institute for Medical Research


Humana Press Inc

Place of publication

999 Riverview Drive Suite 208, Totowa, USA, Nj, 07512

Repository Status

  • Restricted

Socio-economic Objectives

Diagnosis of human diseases and conditions

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