دوره 17، شماره 1 - ( 10-1404 )
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Zhao Y, Jiang H, Shang H, Xia Z. TSH inhibition Drives Hippocampal 5-HT Loss and Notch Activation, Disrupting Neurogene-sis–Apoptosis Balance and Inducing Mood-Related Behaviors in Rats. BCN 2026; 17 (1)
URL: http://bcn.iums.ac.ir/article-1-3374-fa.html
URL: http://bcn.iums.ac.ir/article-1-3374-fa.html
TSH inhibition Drives Hippocampal 5-HT Loss and Notch Activation, Disrupting Neurogene-sis–Apoptosis Balance and Inducing Mood-Related Behaviors in Rats. مجله علوم اعصاب پایه و بالینی. 1404; 17 (1)
چکیده:
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.
نوع مطالعه: Original |
موضوع مقاله:
Behavioral Neuroscience
دریافت: 1404/7/16 | پذیرش: 1404/7/27 | انتشار: 1404/10/30
دریافت: 1404/7/16 | پذیرش: 1404/7/27 | انتشار: 1404/10/30
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