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


CONCLUSIONS
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).


CONCLUSIONS
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.
Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. hosseinim@MUMS.ac.ir
Mahmoud
M
Hosseini
Samaneh Sadat
SS
Dastghaib
Houshang
H
Rafatpanah
Mosa Al-Reza
MA
Hadjzadeh
Hossein
H
Nahrevanian
Ismaeil
I
Farrokhi
D000818:Animals; D013956:Antithyroid Agents; D005260:Female; D006624:Hippocampus / Q000378:metabolism*; D007037:Hypothyroidism / Q000139:chemically induced / Q000378:metabolism*; D007859:Learning Disabilities / Q000378:metabolism*; D008569:Memory Disorders / Q000378:metabolism*; D008713:Methimazole; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013974:Thyroxine / Q000032:analysis; D013997:Time Factors
D013956:Antithyroid Agents; D009569:Nitric Oxide; D008713:Methimazole; D019001:Nitric Oxide Synthase; D013974:Thyroxine
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