Nitric oxide contributes to learning and memory deficits observed in hypothyroid rats during neonatal and juvenile growth

Abstract

INTRODUCTION:Severe cognitive impairment follows thyroid hormone deficiency during the neonatal period. The role of nitric oxide (NO) in learning and memory has been widely investigated.METHODS:This study aimed to investigate the effect of hypothyroidism during neonatal and juvenile periods on NO metabolites in the hippocampi of rats and on learning and memory. Animals were divided into two groups and treated for 60 days from the first day of lactation. The control group received regular water, whereas animals in a separate group were given water supplemented with 0.03% methimazole to induce hypothyroidism. Male offspring were selected and tested in the Morris water maze. Samples of blood were collected to measure the metabolites of NO, NO2, NO3 and thyroxine. The animals were then sacrificed, and their hippocampi were removed to measure the tissue concentrations of NO2 and NO3.DISCUSSION:Compared to the control group's offspring, serum thyroxine levels in the methimazole group's offspring were significantly lower (P<0.01). In addition, the swim distance and time latency were significantly higher in the methimazole group (P<0.001), and the time spent by this group in the target quadrant (Q1) during the probe trial was significantly lower (P<0.001). There was no significant difference in the plasma levels of NO metabolites between the two groups; however, significantly higher NO metabolite levels in the hippocampi of the methimazole group were observed compared to controls (P<0.05).CONCLUSION:These results suggest that the increased NO level in the hippocampus may play a role in the learning and memory deficits observed in childhood hypothyroidism; however, the precise underlying mechanism(s) remains to be elucidated.

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

“…It has been documented that hypothyroidism can lead to a reduced level of glutathione and mitochondrial cytochrome c oxidase activity and overproduction of hydroxyl radicals 9 . Hypothyroidisminduced oxidative damage in the hippocampus and amygdala has also been shown to have deleterious effects on learning and memory processes 10 . Thymoquinone (TQ), the main constituent of the volatile oil of Nigella sativa seeds, is well known to have antioxidant properties 11 .…”

Partial Immunotherapy of Leishmaniasis by in vivo Trial of L-Arginine in Balb/c Mice Infected with Leishmania major via Nitric Oxide Pathway

“…It is concluded that there is a need for compounds with a pharmacological profile in vivo more conducive to the exploitation of the role of NO in Leishmania, including longer biological action and greater selectivity (Nahrevanian et al, 2007). These results demonstrated that L-Arg is not only well recognized as a NO precursor with a safely use to treat physiological condition (Fallahi et al, 2011;Vahedian et al, 2011;Hosseini et al, 2010; Leishmania major after treatment with three types of L-Arg. Positive Geimsa-stained smears of target tissues from control and test groups of mice infected with Leishmania major were counted at the ultimate day of experimental period.…”

Decreased nitric oxide levels in the hippocampus may play a role in learning and memory deficits in ovariectomized rats treated by a high dose of estradiol

“…Direct or indirect effects of estradiol on hippocampal neurons are also attractive as possible mechanisms 27 . NO contributes in hippocampal dependent learning and memory tasks including spatial memory 22,28 . On the other hand, it has been suggested that NO mediates the effects of estradiol in many organs 29 .…”

“…Considering the fact that estradiol affects the release of NO and the NOS isoforms activity in the brain, the interaction of estrogen and NO in nervous system functions is conceivable [14][15][16] . It has been previously shown that NO contributes in sex hormone-dependent changes of behavior [21][22][23][24][25][26][27][28][29][30] . Previous studies also implied that some functions of estrogen in the central nervous system are related to increased NO production 15 .…”

“…The contents were then vortex-mixed and centrifuged, and the supernatants were transferred to a 96-well flat-bottomed microplate. Absorbance was read at 520 nm using a microplate reader, and final values were calculated from standard calibration plots 22 .…”