Effects of treadmill exercise and sex hormones on learning, memory and hippocampal brain-derived neurotrophic factor levels in transient congenital hypothyroid rats

Abstract

Transient thyroid function abnormalities at birth exhibit intellectual developmental and cognitive disorders in adulthood. Given the well-known effects of physical activity and sex hormones on cognitive functions and brain-derived neurotrophic factor (BDNF), the present study examined the effects of treadmill exercise, sex hormones, and the combined treatment on learning and memory and hippocampal BDNF levels in transient congenital hypothyroid rats. To induce hypothyroidism, 6-propyl-2-thiouracil was added to the drinking water from the 6th day of gestation to the 21st postnatal day (PND). From PNDs 28 to 47, female and male pup rats received 17β-estradiol and testosterone, respectively, and about 30 min later, they were forced to run on the treadmill for 30 min once a day. On PNDs 48–55, spatial learning and memory of all rats tested in the water maze, which followed by measurement of BDNF in the hippocampus. Results showed that developmental hypothyroidism induced significant deficits in spatial learning and memory and hippocampal BDNF in both male and female rats. In both male and female hypothyroid rats, exercise and exercise plus sex hormones, but not sex hormones alone alleviated learning and memory deficits and all treatments (exercise, sex hormones, and the combined treatment) increased hippocampal BDNF. These disconnects in the effects of exercise, sex hormones and the combined treatment on behavioral and neurochemical outcomes suggest that a neurochemical mechanism other than hippocampal BDNF might contribute in the ameliorating effects of exercise on learning and memory deficits induced by developmental thyroid hormone insufficiency.

The effects of choline supplementation in mothers with hypothyroidism on the alteration of cognitive–behavioral, long‐term potentiation, morphology, and apoptosis in the hippocampus of pre‐pubertal offspring rats

“…In line with previous studies, we found that maternal hypothyroidism during pregnancy and lactation decreased learning and memory (Rashidy-Pour et al, 2020), as well as LTP (Derafshpour et al, 2019) in rat pups. In the current study, mothers treated with propylthiouracil (PTU) and their hypothyroid pups had significantly lower levels of thyroxine (T4) and higher levels of TSH than the corresponding control groups.…”

“…Dams in the hypothyroid groups were administered the anti‐thyroid agent 6‐propyl‐2‐thiouracil (PTU; Sigma Co., 3050 Spruce St, St. Louis, Missouri, USA) dissolved in drinking water at a concentration of 100 ppm started on the 6th day of gestation (GD 6) and continued throughout lactation until the 21St Postnatal Day (PND 21), while the control group consumed tap water during this period (Derafshpour et al, 2019). This time frame selected for treatment was based on our recent studies, which showed the long‐term exposure of the dams to PTU, extended from early gestation to early adolescence‐induced developmental hypothyroidism in rat pups (Derafshpour et al, 2019; Rashidy‐Pour et al, 2020). The animals in choline‐treated groups received 400.0 mg/kg/day equivalent to two daily doses of 486.6 mg/kg of choline bitartrate by gavage (Derafshpour et al, 2019; Rashidy‐Pour et al, 2020).…”

“…The hippocampus is involved in cognitive skills such as learning and memory (Gerges & Alkadhi, 2004) and is an area rich in thyroid hormone receptors (Shafiee et al, 2016). Changes in thyroid hormone levels are associated with hippocampal‐associated learning and memory disorders (Rashidy‐Pour et al, 2020). Congenital hypothyroidism (CH) is an inborn condition in which the thyroid gland does not produce sufficient thyroid hormones (Cherella & Wassner, 2020).…”

“…Congenital hypothyroidism (CH) is an inborn condition in which the thyroid gland does not produce sufficient thyroid hormones (Cherella & Wassner, 2020). This disease is associated with brain damage and mental retardation (Rashidy‐Pour et al, 2020). CH is classified into two categories: permanent and transient congenital hypothyroidism (TCH).…”

Experimental Modeling Of Hypothyroidism: Principles, Methods, Several Advanced Research Directions In Cardiology

“…The manifestation rate and morphological disorders arising in the structure of organs and tissues is determined by the degree of thyroid hormone deficiency. Most critically, hypothyroidism affects the nervous system [8], cardiovascular system (CVS) [9,10], skin [11,12], locomotor system [13] and sensory organs [3,4,14,15]. Experimental models of hypothyroidism are widely used to study morphofunctional disorders in hypothyroidism and conduct preclinical assessment of the medical-preventive activities effectiveness.…”