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1- Clinical Medical College of China-Japan Friendship Hospital, Beijing University of Chinese Medi-cine, China.
2- Department of Acupuncture and Mini-invasive Oncology, Beijing University of Chinese Medi-cine Third Affiliated Hospital, Beijing, China.
3- Department of Chinese Medicine Surgery, China-Japan Friendship Hospital, Beijing, China.
2- Department of Acupuncture and Mini-invasive Oncology, Beijing University of Chinese Medi-cine Third Affiliated Hospital, Beijing, China.
3- Department of Chinese Medicine Surgery, China-Japan Friendship Hospital, Beijing, China.
Abstract:
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.
Type of Study: Original |
Subject:
Behavioral Neuroscience
Received: 2025/10/8 | Accepted: 2025/10/19
Received: 2025/10/8 | Accepted: 2025/10/19
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