Development of brainstem 5HT(1A) receptor-binding sites in serotonin-deficient mice

作者：Massey Caitlin A; Kim Gloria; Corcoran Andrea E; Haynes Robin L; Paterson David S; Cummings Kevin J; Dymecki Susan M; Richerson George B; Nattie Eugene E; Kinney Hannah C; Commons Kathryn G^*

来源：Journal of Neurochemistry, 2013, 126(6): 749-757.

DOI：10.1111/jnc.12311

• autoreceptors
• heteroreceptors
• Lmx1b
• Pet1
• raphe
• sudden infant death syndrome

The sudden infant death syndrome is associated with a reduction in brainstem serotonin 5-hydroxytryptamine (5-HT) and 5-HT1A receptor binding, yet it is unknown if and how these findings are linked. In this study, we used quantitative tissue autoradiography to determine if post-natal development of brainstem 5-HT1A receptors is altered in two mouse models where the development of 5-HT neurons is defective, the Lmx1b(f/f/p), and the Pet-1(-/-) mouse. 5-HT1A receptor agonistbinding sites were examined in both 5-HT-source nuclei (autoreceptors) and in sites that receive 5-HT innervation (heteroreceptors). In control mice between post-natal day (P) 3 and 10, 5-HT1A receptor binding increased in several brainstem sites; by P25, there were region-specific increases and decreases, refining the overall binding pattern. In the Lmx1b(f/f/p) and Pet-1(-/-) mice, 5-HT1A-autoreceptor binding was significantly lower than in control mice at P3, and remained low at P10 and P25. In contrast, 5-HT1A heteroreceptor levels were comparable between control and 5-HT-deficient mice. These data define the post-natal development of 5-HT1A-receptor binding in the mouse brainstem. Furthermore, the data suggest that 5-HT1A-heteroreceptor deficits detected in sudden infant death syndrome are not a direct consequence of a 5-HT neuron dysfunction nor reduced brain 5-HT levels.

• 出版日期2013-9