Thyroid hormone metabolism in the cortex of male and female APP knock-in mice
2023
Authors:
Ćirić, JelenaMilovanović, Nikola
Jovanović Macura, Irena
Tešić, Vesna
Filipović, Branko
Šošić-Jurjević, Branka
Perović, Milka
Contributors
Kanazir, SelmaSavić, Danijela
Document Type:
Conference object (Published version)
,
© 2023 by Serbian Neuroscience Society and associates
Metadata
Show full item recordAbstract:
Targeting novel pathways contributing to the pathogenesis/progression of Alzheimer’s
disease (AD) is crucial due to the lack of effective management and treatment
modalities. Higher prevalence, progression rate and severity of AD in women than in
men also establish sex as key variable in AD therapy development.
Thyroid disorders, both hyper- and hypothyroidism, were found to occur with up to
nine-fold higher prevalence in women compared to men. The molecular mechanisms
by which thyroid dysfunction contribute to AD pathogenesis and heterogeneity remain
however elusive. We therefore examined sex-related alterations in gene expression of
iodothyronine deiodinase 2 (Dio2) and transthyretin (TTR) involved in the tissue
metabolism and the distribution of thyroid hormones (THs), respectively, in a novel,
state-of the art knock-in (KI) mouse model of AD-like amyloidosis, APPNL-G-F mice.
Quantitative RT-PCR analysis revealed prominent differences in cortical Dio2 and
TTR gene expression in 9-month-old male and female APPNL-G-F mice and their non KI littermates (WT). In comparison to WT male mice, the increase in Dio2 mRNA
level was evident in female WT mice, while a trend toward a decrease was detected in
their APPNL-G-F KI littermates. Expression in the opposite direction was observed for
TTR, with a robust genotype-dependent decrease in male mice.
Results are in line with well-established role of THs in the regulation of neuronal
plasticity in the adult brain and suggest profound sex-biased effects of TH on Aβ induced pathology in APPNL-G-F mice.
Keywords:
Thyroid hormone metabolism; Alzheimer's disease; Sex differencesFunding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200007 (University of Belgrade, Institute for Biological Research 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
In:
- Kanazir S, Savić D, editors. Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia. Belgrade: Serbian Neuroscience Society; 2023. p. 111.