Brain‑derived neurotrophic factor and nitric oxide contribute to protective effects of rosiglitazone on learning and memory in hypothyroid rats

Abstract

The effects of the well-known peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist rosiglitazone (Rosi) on brain-derived neurotrophic factor (BDNF), nitric oxide (NO), and learning and memory were investigated in hypothyroid rats.Hypothyroidism was induced in immature Wistar rats by administration of propylthiouracil in drinking water. Rats were divided into four groups: control, hypothyroid, and hypothyroid treated with Rosi at doses of 2 mg/kg or 4 mg/kg. Memory was then assessed by the Morris water maze (MWM) and passive avoidance (PA) tests. Following anesthetization, brain samples were collected for biochemical measurements. Hypothyroidism increased the escape latency and traveled path in the learning trials of the MWM and decreased the time spent and the distance traveled in the target quadrant on the probe day. Hypothyroidism also impaired the avoidance behavior of rats in the PA test. Rosi improved the performance of rats in both MWM and PA tasks.Hypothyroidism also decreased hippocampal BDNF levels, increased NO metabolites, and induced oxidative damage in the brain.Treatment of hypothyroid rats with both doses of Rosi increased BDNF levels and decreased NO metabolites and malondialdehyde concentrations. In addition, thiol content and superoxide dismutase and catalase activities were increased in the brain regions of hypothyroid rats receiving Rosi. The administration of 4 mg/kg Rosi also significantly increased serum thyroxin levels. The results of the present study showed that BDNF and NO play a role in the protective effects of Rosi against learning and memory impairment in hypothyroid rats.

The effects of PPARγ agonists on long-term potentiation and apoptosis in the hippocampus area of juvenile hypothyroid rats

“…Based on the results of the present study, we also found that treating animals with POG or RSG lead to a decrease in NO levels in the hippocampal tissue, which can be considered as one of the possible mechanisms for useful effects of activating PPARγ. These results are in agreement with our previous studies, which showed that POG or RSG decreased NO levels in brain tissues (Baghcheghi et al 2021, Franco et al 2006, Venditti & Di Meo 2006. Therefore, in the present study, we can imply that POG or RSG, probably by diminishing NO, prevent apoptosis and LTP impairment in hippocampal tissue of hypothyroid rat.…”

Ashwagandha Roots Extract Attenuate Some Anatomical and Behavioral Outcomes in Rat’ Pups After Early Postnatal Induction of Hypothyroidism

“…In PND 9, the statistical analysis by one -way ANOVA at p≤0.05 showed that the mean time that pups were needed to reach the home bedding was (10.33 ± 3.02) sec in pups of control group, while those pups of hypothyroid groups(hypothyroid without treatment , hypothyroid treated with levothyroxine and hypothyroid treated with Ashwagandha Roots extract) were (40.83±14.428), (38.13±14.397), and (41.6±11.415) sec., respectively. These results showed that the time required for the pups of hypothyroid groups (2,3,4) to reach maternal bedding was much longer than time of the control group pups (1). Fig.…”

“…Severe cognitive impairment comes from congenital hypothyroidism [2]. Moreover, there is evidence that neurocognitive impairments may continue even when early detection and therapy have been found to improve many of these problems [3]. Numerous studies show that thyroid hormones influence a variety of behaviors throughout life by acting in multiple brain areas both during development and in maturity [4].…”

“…Numerous studies show that thyroid hormones influence a variety of behaviors throughout life by acting in multiple brain areas both during development and in maturity [4]. Thyroid hormones, for instance, have an impact on the cerebellum's granule cell proliferation and migration, synaptogenesis, and dendritic development of cerebellar Purkinje cells [1,3]. Thyroid hormone deficiency throughout development therefore causes disturbed motor coordination in adults.…”

Vitamin E prevented hepatic and renal tissue damage in hypothyroid rats

“…Indeed, different studies have also affirmed an oxidative stress status followed by hypothyroidism. [ 12 13 ] It has been well documented that experimentally induced hypothyroidism leads to an imbalance of production ROS by mitochondria and oxidant enzymes and, scavenging of ROS by the antioxidant system in tissues like the liver interrupted. [ 14 ] Furthermore, it was shown that acute liver failure is connected with enhanced blood endotoxins and pro-inflammatory cytokines and chemokines that are followed by dysfunction of the thyroid gland.…”