ABSTRACT
Alzheimer disease's (AD) is a neurodegenerative disorder characterized by cognitive and behavioral impairment. The central nervous system is an important target of thyroid hormones (TH). An inverse association between serum triiodothyronine (T3) levels and the risk of AD symptoms and progression has been reported. We investigated the effects of T3 treatment on the depression-like behavior in male transgenic 3xTg-AD mice. Animals were divided into 2 groups treated with daily intraperitoneal injections of 20 ng/g of body weight (b.w.) L-T3 (T3 group) or saline (vehicle, control group). The experimental protocol lasted 21 days, and behavioral tests were conducted on days 18-20. At the end of the experiment, the TH profile and hippocampal gene expression were evaluated. The T3-treated group significantly increased serum T3 and decreased thyroxine (T4) levels. When compared to control hippocampal samples, the T3 group exhibited attenuated glycogen synthase kinase-3 (GSK3), metalloproteinase 10 (ADAM10), amyloid-beta precursor-protein (APP), serotonin transporter (SERT), 5HT1A receptor, monocarboxylate transporter 8 (MCT8) and bone morphogenetic protein 7 (BMP-7) gene expression, whereas augmented superoxide dismutase 2 (SOD2) and Hairless gene expression. T3-treated animals also displayed reduced immobility time in both the tail suspension and forced swim tests, and in the latter presented a higher latency time compared to the control group. Therefore, our findings suggest that in an AD mouse model, T3 supplementation promotes improvements in depression-like behavior, through the modulation of the serotonergic related genes involved in the transmission mediated by 5HT1A receptors and serotonin reuptake, and attenuated disease progression.
Subject(s)
Alzheimer Disease , Triiodothyronine , Animals , Mice , Male , Triiodothyronine/pharmacology , Triiodothyronine/therapeutic use , Alzheimer Disease/metabolism , Depression/drug therapy , Glycogen Synthase Kinase 3 , Mice, Transgenic , Thyroid Hormones/metabolism , Disease Models, AnimalABSTRACT
Exercise reduces sympathetic activity (SA), arterial pressure and heart rate in spontaneously hypertensive rats (SHR). Exercise increases oxidative stress (OS) and inflammation is implicated in the generation of reactive oxygen species (ROS) and progression of hypertension. To unravel these effects of exercise and considering that SA is driven by medullary areas, we hypothesized that swimming exercise (SW) affects the gene expression (g.e.) of proteins involved in inflammation and OS in the commissural Nucleus of the Solitary Tract (cNTS) and Rostral ventrolateral medulla (RVLM), which control the sympathetic outflow in SHR. We used male SHR and Wistar rats (14-16wks-old) which were maintained sedentary (SED) or submitted to SW (1 h/day, 5 days/wk./6wks). The g.e. of cycloxygenase-2 (COX-2), interleukin 6 (IL-6), interleukin 10 (IL-10), AT-1 receptor (AT-1r), neuroglobin (Ngb) and cytoglobin (Ctb) in cNTS and RVLM was carried out by qPCR. We observed that COX-2 g.e. increased in SW-SHR in cNTS and RVLM compared to SED-SHR. The IL-6 g.e. reduced in RVLM in SW-SHR, whereas IL-10 g.e. increased in SW-SHR in comparison to SED-SHR. The AT-1r g.e. decreased in SW-SHR in cNTS and RVLM compared to SED-SHR. The Ngb and Ctb g.e. in cNTS neurons increased in SHR and Wistar rats submitted to SW compared to SED, but only Ctb g.e. increased in RVLM in SW-SHR and Wistar in comparison to SED. Therefore, the SW altered the g.e. in cNTS and RVLM for reducing the inflammation and ROS formation, which is increased particularly in SHR, consequently decreasing the OS.
