Irisin treatment lowers levels of phosphorylated tau in the hippocampus of pre-symptomatic female but not male htau mice.

Title

Irisin treatment lowers levels of phosphorylated tau in the hippocampus of pre-symptomatic female but not male htau mice.

Creator

Bretland KA; Lin Li; Bretland KM; Smith MA; Fleming SM; Dengler-Crish CM

Publisher

Neuropathology And Applied Neurobiology

Date

2021
2021-03-26

Description

AIMS: Irisin is a hormone cleaved from fibronectin type-III domain-containing protein 5 in response to exercise and may be therapeutic in Alzheimer's disease (AD). Irisin is shown to repair damage caused by midlife cardiometabolic risk factors for AD (i.e., diabetes mellitus; hypertension), prevent neural amyloid beta aggregation, and reduce neuroinflammation. However, there are no investigations of irisin's effect on AD-associated tauopathy in the brain. This study begins to address this gap in knowledge. METHODS: Transgenic htau mice that selectively develop age-related tauopathy were treated with recombinant irisin (100 ug/kg weekly i.p.) beginning at a pre-symptomatic age (4 months) to determine if irisin could prevent emergence of early neuropathology. One month later, mice were sacrificed to collect brain tissue and serum. Protein levels of ptau (serine 202), inflammatory cytokine tumour necrosis factor alpha (TNFα) and FNDC5 were quantified using capillary-based western blotting (Wes). RESULTS: Our data show that irisin treatment significantly reduced ptau and TNFα in hippocampus and serum of female htau mice compared to vehicle-treated controls. Irisin treatment did not alter ptau levels in male htau hippocampus and appeared to enhance both neural and systemic TNFα levels. CONCLUSIONS: This study provides the first evidence that enhancing the endogenous hormone irisin may be therapeutic against emerging neuropathology in a tauopathy-selective AD model. This is important because there are currently no disease-modifying therapeutics available for AD, and few agents in development address the multiple disease targets irisin appears to-making irisin an intriguing therapeutic candidate for further investigation.

Subject

Alzheimer disease; anti-inflammatory agents; Dementia; metabolic diseases; neurofibrillary tangles; physical exertion; tauopathies

Identifier

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Format

journalArticle

Search for Full-text

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ISSN

1365-2990 0305-1846

NEOMED College

NEOMED College of Pharmacy

NEOMED Department

Department of Pharmaceutical Sciences
NEOMED Student Publications

Update Year & Number

April 2021 List

Citation

Bretland KA; Lin Li; Bretland KM; Smith MA; Fleming SM; Dengler-Crish CM, “Irisin treatment lowers levels of phosphorylated tau in the hippocampus of pre-symptomatic female but not male htau mice.,” NEOMED Bibliography Database, accessed July 27, 2021, https://neomed.omeka.net/items/show/11620.

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