Subclinical Hypothyroidism In Pregnant Rats Impaired Learning And Memory In Offspring By Promoting P75^NTR Signaling

Objective:Thyroid hormones plays a critical role in fetal brain development.Maternal hypothyroidism during pregnancy can affect neurodevelopment in their offspring,and it can’t be reversed in the future.Leading to the impairment of learning and memory ability of offspring.Previous studies by our group found that when subclinical hypothyroidism（SCH）occurred during pregnancy,the neurodevelopment of offspring was limited significantly.However,any potential mechanism has not been reported to elucidate its neurological changes.This study aimed to investigate the effects of maternal subclinical hypothyroidism（SCH）on spatial learning and memory,and its relationship with the apoptotic factors in cerebral cortex of the offspring.Methods:190-210 g female adult Wistar rats were randomly divided into three groups（n=15 per group）,control（CON）group,SCH group,and overt hypothyroidism（OH）group.Rats in the OH and SCH groups were underwent thyroidectomy.CON rats underwent sham thyroid surgery.One month after surgery,rats in the SCH group were injected subcutaneously with L-thyroxine on the back or neck daily.Rats in the CON and OH groups were injected subcutaneously with physiological saline.After 9 days of injections,all rats were mated with normal male rats（male:female=1:2）.Spatial learning and memory in the offspring were evaluated by long-term potentiation（LTP）and Morris water maze（MWM）test on 40 days of pups.Protein expression of the p75neurotrophin receptor(p75^NTR),phospho-c-Jun N-terminal kinase（p-JNK）,and the pro-apoptotic proteins p53 and Bax were detected by western blotting on 7 days of pups’cerebral cortex.Results:The pups in the SCH and OH groups showed longer escape latencies in the MWM,and decreased field-excitatory post synaptic potentials in LTP tests compared with those in the CON group.p75^NTR,p-JNK,p53 and Bax expression levels in the cerebral cortex increased in pups in the SCH and OH groups compared with those in the CON group.Conclusions:Maternal SCH during pregnancy may impair spatial learning and memory in the offspring,and may be associated with the increased apoptosis in the cerebral cortex.