Lateral Habenular Nucleus Mediates The Role Of T3 In Improving Depression-like Behavior Caused By Hypothyroidism

Thyroid hormones are hormones secreted by the thyroid gland,including triiodothyronine(T3)and tetraiodothyronine(T4).In the body,thyroid hormones elaborate its function by converting T4 to T3,and the activity of T3 is about 50 times that of T4.Twenty percent of T3 is secreted directly by the thyroid gland,while the remaining 80% is produced by peripheral deiodination of T4.It acts mainly in the body by binding to a thyroxine receptor with high affinity,which in turn affects the growth and development of the body.It plays a vital role in the development,metabolism and function of the central nervous system.Thyroid dysfunction is often associated with emotional and mental disorders.Patients with hypothyroidism are often accompanied by depression-like behaviors with sluggish expression,apathy,and desperate behavior.Conversely,people with depression are more prone to hypothyroidism than normal people.Therefore,exploring the neuropathological mechanism of depression caused by hypothyroidism will undoubtedly have important clinical significance for improving depression-like symptoms in patients with hypothyroidism.In recent years,the important role of lateral habenular nucleus(LHb)in the pathogenesis of depression has attracted widespread attention.Studies have shown that Thyroid Hormone Receptor β(TRβ)is widely and unevenly distributed in the brain,with the highest level of distribution in the olfactory bulb and the habenular nucleus.However,whether LHb can directly mediate the occurrence of depression-like behavior caused by hypothyroidism has not been fully elucidated.In this experiment,we used propylthiouracil(PTU)to induce hypothyroidism in rats,and defecteded depression-like symptoms by behavioral tests;Then,histochemistry and Real-time PCR were used to detect the changes of LHb activity and the expression of TRβ receptor in rats with hypothyroidism and depression-like symptoms.Finally,the improvement of depression-like behavior was observed by microinjection of T3 in LHb.The results showed that,firstly,the water consumption,food intake and body weight of the rats with PTU-induced hypothyroidism were lower than those of the control group,and the serum levels of T3 and T4 were decreased,suggesting thatthe model of hypothyroidism was established successfully.Afterwards,we performed open field test,sucrose preference,and forced swimming behavioral experiments in the PTU group and the control group,and found that the rats of PTU group showed depression-like behavior.The cytochrome oxidase staining of LHb tissue was further carried out,and it was found that the activity of LHb neurons was increased in the PTU group compared with the control group;Moreover,in the Real-time PCR experiment,the expression of TRβ in LHb was significantly decreased in the PTU group compared with the control group.These results indicate that thyroid hypopnea rats are associated with depression-like behavior,and LHb is closely related to this.Finally,after microinjection of T3 into LHb in rats in the PTU group,behavioral tests were performed to observe whether depression-like behavior was improved immediately or 12 hours after administration.The experimental results showed that the depression-like symptoms of PTU-induced hypothyroidism rats were rapidly improved after T3 administration,and the improvement effect disappeared after 12 hours.In conclusion,PTU-induced hypothyroidism in rats showed depression-like behavior.At this time,the activity of neurons in LHb increased,while the expression of TRβ decreased.Administration of T3 in LHb can rapidly improve depression-like symptoms in hypothyroidism.