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
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Format
journalArticle
URL Address
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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 April 19, 2024, https://neomed.omeka.net/items/show/11620.