en Behavioral Neuroscience Behavioral Neuroscience Original Original <div style="text-align: justify;"><span style="line-height:2;"><span style="font-size:14px;"><span style="font-family:Tahoma;"><span style="color:black">Therapeutic suppression of thyroid-stimulating hormone (TSH) is widely used after thyroidectomy, but its neurobehavioral impact remains unclear. We investigated emotion-related behaviors and hippocampal mechanisms in rats assigned to blank control, TSH replacement, or TSH inhibition following total thyroidectomy with graded levothyroxine. Open-field and tail-suspension tests indexed behavior; ELISA quantified serum FT3/FT4/TSH and hippocampal 5-HT; BrdU with Nestin/NeuN/GFAP assessed neurogenesis; qPCR/Western blot measured Notch1, HES1/HES5, Jagged-1, and Bax/Bcl-2. Compared with control/replacement, TSH inhibition produced anxiety-/depression-like phenotypes, elevated FT3/FT4 with reduced TSH, and decreased hippocampal 5-HT. Notably, Notch signaling was upregulated and functionally linked to behavior by biasing neural stem-cell fate away from neurons toward astrocytes and curtailing neurogenesis, a cellular change that maps onto the observed anxiety-/depression-like outcomes. Concomitantly, an increased Bax/Bcl-2 ratio indicated a pro-apoptotic shift that undermines hippocampal plasticity, providing an additional mechanistic bridge to the behavioral phenotype. Together, reduced 5-HT (upstream), Notch-driven suppression of neuronal differentiation, and heightened apoptosis converge to impair hippocampal circuit integrity, offering a coherent molecular-to-behavioral pathway for mood-related effects under TSH suppression. These findings suggest that long-term TSH inhibition may carry neuropsychiatric risks and support routine monitoring of mood and cognition in patients receiving suppressive regimens.</span></span></span></span><br> &nbsp;</div> TSH inhibition, Open field, Tail suspension, 5-HT, Notch, Neurogenesis, Bax/Bcl-2 0 0 http://bcn.iums.ac.ir/browse.php?a_code=A-10-8389-1&slc_lang=en&sid=1 Yikun Zhao 18810056325@163.com 13700319475328460057571 13700319475328460057571 No Clinical Medical College of China-Japan Friendship Hospital, Beijing University of Chinese Medi-cine, China. Honglin Jiang 20210941334@bucm.edu.cn 13700319475328460057572 13700319475328460057572 No Department of Acupuncture and Mini-invasive Oncology, Beijing University of Chinese Medi-cine Third Affiliated Hospital, Beijing, China. Huiyuan Shang shyuanll@163.com 13700319475328460057573 13700319475328460057573 No Clinical Medical College of China-Japan Friendship Hospital, Beijing University of Chinese Medi-cine, China. Zhongyuan Xia 2718421708@qq.com 13700319475328460057574 13700319475328460057574 Yes Department of Chinese Medicine Surgery, China-Japan Friendship Hospital, Beijing, China.