title: Development of brainstem 5-HT1A receptor-binding sites in serotonin-deficient mice.
abstract: The sudden infant death syndrome is associated with a reduction in brainstem serotonin 5-hydroxytryptamine (5-HT) and 5-HT(1A) 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-HT(1A) 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-HT(1A) receptor agonist-binding 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-HT(1A) 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-HT(1A)-autoreceptor binding was significantly lower than in control mice at P3, and remained low at P10 and P25. In contrast, 5-HT(1A) heteroreceptor levels were comparable between control and 5-HT-deficient mice. These data define the post-natal development of 5-HT(1A)-receptor binding in the mouse brainstem. Furthermore, the data suggest that 5-HT(1A)-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. To elucidate the developmental relationship between serotonin (5-HT) levels and 5-HT(1A) receptors in the brainstem, we examined 5-HT(1A) binding in two 5-HT-deficient mouse models. In nuclei containing 5-HT neurons, 5-HT(1A) binding was decreased (autoreceptors), while binding was maintained in projection sites (heteroreceptors). Thus, brainstem 5-HT(1A)-heteroreceptor-binding sites do not appear developmentally sensitive to reduced brain 5-HT levels.
authors.affiliation: Department of Anesthesiology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Caitlin A
authors.initials: CA
authors.lastname: Massey
authors.forename: Gloria
authors.initials: G
authors.lastname: Kim
authors.forename: Andrea E
authors.initials: AE
authors.lastname: Corcoran
authors.forename: Robin L
authors.initials: RL
authors.lastname: Haynes
authors.forename: David S
authors.initials: DS
authors.lastname: Paterson
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Cummings
authors.forename: Susan M
authors.initials: SM
authors.lastname: Dymecki
authors.forename: George B
authors.initials: GB
authors.lastname: Richerson
authors.forename: Eugene E
authors.initials: EE
authors.lastname: Nattie
authors.forename: Hannah C
authors.initials: HC
authors.lastname: Kinney
authors.forename: Kathryn G
authors.initials: KG
authors.lastname: Commons
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D001933:Brain Stem / Q000254:growth & development* / Q000378:metabolism*; D003627:Data Interpretation, Statistical; D005838:Genotype; D060850:LIM-Homeodomain Proteins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D011903:Raphe Nuclei / Q000378:metabolism; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D012701:Serotonin / Q000172:deficiency*; D014157:Transcription Factors / Q000235:genetics
chemical_list: C484684:Fev protein, mouse; C112149:LIM homeobox transcription factor 1 beta; D060850:LIM-Homeodomain Proteins; D014157:Transcription Factors; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin
keywords: Lmx1b; Pet1; autoreceptors; heteroreceptors; raphe; sudden infant death syndrome