The regulation of pituitary-thyroid abnormalities by peripheral administration of levothyroxine increased brain-derived neurotrophic factor and reelin protein expression in an animal model of Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) is associated with decreased serum levels of thyroid hormones (THs), increased levels of thyroid-stimulating hormone (TSH), and decreased protein expression of brain-derived neurotrophic factor (BDNF) and reelin in the hippocampus. In this study, we have evaluated the effect of subcutaneous administration of levothyroxine (L-T4) on levels of THs and TSH as well as protein expression of BDNF and reelin in AD rats. To make an animal model of AD, amyloid-beta peptide (Aβ) plus ibotenic acid were infused intrahippocampally, and rats were treated with L-T4 and (or) saline for 10 days. The levels of THs and TSH were measured by ELISA kits. Protein synthesis was detected by Western blotting method. Results have been shown that serum level of THs, BDNF, and reelin protein expression in the hippocampus were significantly decreased (P < 0.001) in AD animals and elevated significantly in AD rats treated with L-T4 (P < 0.01). Data showed that TSH level significantly decreased in AD rats treated with L-T4 (P < 0.05). These findings indicated that L-T4 increased BDNF and reelin protein expression by regulation of serum THs and TSH level in Aβ-induced AD rats.

Role of the Extracellular Matrix in Alzheimer’s Disease

“…Acid (HA) ↑ Nielsen et al (2012), Nägga et al (2014), Li et al (2017), and Reed et al (2019) Heparin Sulfate Proteoglycan (HSPG) ↑ Van Horssen et al (2003), Shimizu et al (2009), and Lorente-Gea et al (2020) Chondroitin Sulfate Proteoglycan (CSPG) ↑ Shimizu et al (2009) and Goetzl et al (2019) Keratan Sulfate Proteoglycan (KSPG) ↓ Lindahl et al (1996) and Snow et al (1996) Dermatan Sulfate Proteoglycan (DSPG) ↑ Shimizu et al (2009) and Genedani et al (2010) Tenascin C (TNC) ↑ Xie et al (2013), Hondius et al (2016), and Hasanzadeh et al (2021) Tenascin R (TNR) ↑ Manavalan et al (2013) and Végh et al (2014) Reelin ↓ Herring et al (2012),Mota et al (2014), andShabani et al (2018) …”

Iodide intake during pregnancy and lactation stimulates KLF9, BDNF expression in offspring brain with elevated DHA, EPA metabolites

“…KLF9 is necessary for Purkinje cell survival in organotypic culture, and mediates TH-dependent inhibition of axonal regeneration in the cerebellum as well [ 27 ]. Brain-derived neurotrophic factor (BDNF) is a downstream effector of KLF9 signaling (BDNF), which plays an important role in neuronal survival, differentiation, and synaptic plasticity in the brain [ 28 ].…”

Association between Serum Brain-derived Neurotrophic Factor and 25-OH Vitamin D Levels with Vitamin D Receptors Gene Polymorphism (rs2228570) in Patients with Autoimmune Thyroiditis and Hypothyroidism

“…BDNF significantly impacts memory formation and brain development, namely, neurogenesis, synaptogenesis, and neuronal differentiation [16]. Previous investigations have detected that thyroid hormones play an essential role in BDNF expression [17]. An essential method used for identifying a hereditary predisposition to certain diseases is based on the analysis of transcriptome [18], [19] and single-nucleotide polymorphism [20], [21], [22].…”