Adverse Outcome Pathway on inhibition of Na+/I‑ symporter (NIS) leads to learning and memory impairment

The thyroid hormones (TH) are essential for brain development, maturation, and function as they regulate the early key developmental processes. Normal human brain development and cognitive function relays on sufficient production of TH during the perinatal period. The function of Na⁺/I^- symporter (NIS) is critical for the physiological production of TH levels in the serum. The present AOP describes causative links between inhibition of NIS function leading to the decreased levels of TH in the blood and consequently in the brain, causing learning and memory deficit in children. Learning and memory depend upon the coordinated action of different brain regions and neurotransmitter systems creating functionally integrated neural networks. Hippocampus and cortex are the most critical brain structures involved in the process of cognitive functions. The function of NIS and its essentiality for TH synthesis is well known across species, however, quantitative information of KERs is limited.