Study On Cerebral Dopamine D1-like Receptor Expression And Adulthood Behaviors Alteration In Mice With Hypothyroidism In Early Development

Hypothyroidism in early development can cause disorders in the mental development, neurological function and metabolism。In severe cases, it can cause irreversible brain damage, which appeared neurological and psychiatric symptoms, including depress, apathetic, memory and cognitive retardation. Dopamine as an important neurotransmitter in the brain, involved in regulation of movement, cognition, emotion, positive reinforcement and other related behaviors. Existed studies show that hypothyroidism can lead to dopamine dysfunction in the brain. But the key point time, reversibility, and the dopamine-related behavior changes in adulthood caused by hypothyroidism, haven't yet see a clear report at home and abroad. Establish hypothyroid mice model in early development to study the impact of hypothyroidism in early development (gestation and lactation period) on brain dopamine D1-like receptors and its reversibility, moreover investigating the dopamine-related behavioral changes induced by hypothyroidism.Methods(1) Oral administration of the 0.03% methimazole (MMI) in drinking water to establish the hypothyroid mice model. According to treatment conditions, mice assigned to different groups, persistent hypothyroid group (pregnant 10 days to death with MMI water), early hypothyroid group (pregnant 10 days to postnatal 7 days with MMI water) and the control group (with distilled water). The serum T3T4 index and weight level had been detected. (2) Real time RT-PCR study for detection of brain dopamine Dl-like receptor mRNA expression levels.(3) Western Blot study examined brain dopamine D1-like receptor protein expression.(4) 50-day-old pups (adulthood) with Open field test to study dopamine-related behavior change.Results(1) As the pups aged, the weights of hypothyroid pups were lower than that recorded for age-matched control pups (P＜0.001). Early hypothyroid pups had higher body weight than hypothyroid pups, but lower than the control group (P＜0.001).(2) Dopamine Dl receptor mRNA expression was significantly lower in hypothyroid pups at P7 to P60 (P＜0.05). D5 receptor mRNA expression was significantly lower in hypothyroid pups at P7 to P21 (P＜0.05) with a correction at P60, when in early hypothyroid group the correction was happened from P21.(3) Dopamine D1 receptor protein expression of hypothyroid pups decreased at P14 to P60(P＜0.05). D5 receptor protein expression decreased in hypothyroid group at P7 to P60 (P＜0.05), with a correction in early hypothyroid group at P60.(4) 50-day-old persistent hypothyroid pups showed a decrease of rearing and grooming, as well as an increase of stretching back and spin turn (P＜0.05).50-day-old early hypothyroid pup reduce the total ambulation, while frequency of spin turn significantly increased (P＜0.05).Conclusion(1) The hypothyroid pups showed a significantly retardation in growth and development. After thyroid function returned to normal, the development level may be increased, but it still lagged behind the normal group.(2) Dopamine D1/D5 receptor mRNA expression and protein expression in hypothyroid pups brain were reduced in varying degrees. The inhibition of dopamine D1 receptor expression caused by hypothyroidism in early development is irreversible. The expression of dopamine D5 receptor can be restored gradually with the thyroid function recovery.(3) Hypothyroidism can induce dopamine-related cognitive and emotion behavioral disorders. Dopamine-related behavioral changes caused by hypothyroidism in early development were partly irreversible.