Levothyroxin restores hypothyroidism‐induced impairment of hippocampus‐dependent learning and memory: Behavioral, electrophysiological, and molecular studies

Abstract

Hypothyroidism induces cognitive impairment in experimental animals and patients. Clinical reports are conflicting about the ability of thyroid hormone replacement therapy to fully restore the hypothyroidism-induced learning and memory impairment. In this study, we investigated the effects of L-thyroxin (thyroxin) treatment on hippocampus-dependent learning and memory in thyroidectomized adult rats. In the radial arm water maze (RAWM) task, thyroxin treated thyroidectomized animals made significantly fewer errors than the untreated hypothyroid animals in Trial 3 of the acquisition phase, short-term memory and long-term memory tests. In addition, the number of errors made by the thyroxin treated thyroidectomized animals was not different from that of the control group. Furthermore, the days-to-criterion (DTC) values for thyroxin treated thyroidectomized animals were not different from those of the control group but significantly lower than those of the untreated hypothyroid animals. In anesthetized rats, extracellular recording from hippocampal area CA1 of hypothyroid rats shows that thyroxin treatment restores impaired Late-phase long-term potentiation (L-LTP). Immunoblot analysis of signaling molecules, including cyclic-AMP response element binding protein (CREB), mitogen-activated protein kinases (MAPKp44/42; ERK1/2), in area CA1 revealed that thyroxin treatment reversed hypothyroidism-induced reduction of signaling molecules essential for learning and memory, and L-LTP. This study shows that thyroxin treatment reverses hypothyroidism-induced impairment of hippocampus-dependent cognition, and L-LTP, probably by restoring the levels of signaling molecule important for these processes.

Thymoquinone reverses learning and memory impairments and brain tissue oxidative damage in hypothyroid juvenile rats

“…Reduced levels . In addition, researchers have shown that thyroxine improved performances of rats in a radial arm maze task and ameliorated long-term potentiation impairments in the CA1 area of the hippocampus when it was administered to thyroidectomized rats 21 . These scientific findings support the results of our study that PTU-induced hypothyroidism disrupted learning and memory in both the Morris water maze and passive avoidance tasks in rats.…”

Changes in spatial memory and BDNF expression to concurrent dietary restriction and voluntary exercise

“…The RAWM is a black circular water tub with six V-shaped stainless steel structures arranged to form a swimming field of an open central area and six swim paths (Diamond et al, 1999;Gerges et al, 2004;Alzoubi et al, 2006;Alzoubi et al, 2009). The water temperature was maintained at 248C 6 18C.…”

Acute nicotine treatment prevents rem sleep deprivation‐induced learning and memory impairment in rat

“…Nicotine, the main component in tobacco, was reported to alleviate impairment of memory associated with psychosocial stress (Aleisa et al, 2006c;Alzoubi et al, 2009b), aging (Carrasco et al, 2006), hypothyroidism (Alzoubi et al, 2005(Alzoubi et al, , 2009a), Alzheimer's disease (Jones et al, 1992;White and Levin, 1999;Srivareerat et al, 2009), Parkinson's disease (Kelton et al, 2000), schizophrenia (Smith et al, 2002;Harris et al, 2004;Jubelt et al, 2008), and attention deficit/hyperactivity disorder (ADHD; Poltavski and Petros, 2006;Potter and Newhouse, 2008). In the hippocampus, nicotine facilitates the induction of LTP in the CA1 region of rat hippocampal slices (Fujii et al, 1999;He et al, 2003) and induces long lasting potentiation in intact mouse DG region (Sawada et al, 1994).…”