Expression of serotonin transporter protein in developing rat brain.
Serotonin transporter (5-HTT), a transmembrane protein, has been shown in adult brain to be distributed not only on synaptic terminals but to a great extent on axons as well. Here we report the ontogeny of 5-HTT and its relationship with serotonin (5-HT) neurons using established 5-HTT and 5-HT antibodies. Both 5-HTT- and 5-HT-immunostaining (-im) appear in 5-HT neurons at embryonic day 12 (E12) in rostral raphe nuclei (RRN). Soon after appearing, 5-HTT-im is highly expressed on axons, similar to adult expression. However, in contrast to adult, 5-HTT-im also outlines the soma-dendrites. Rich 5-HTT-im appears along the entire length of projecting axons, extending to the growth tip. In the next 2 days, intensive 5-HTT-im axons from RRN travel a course preferentially in the floor plate and later, the medial forebrain bundle trajectory. A group of new 5-HT-im neurons and 5-HTT-im axons appear at E13 in caudal raphe nuclei. At E16-18, taking the exact trajectory course of 5-HT axons, 5-HTT-im axons reach ganglionic eminence, olfactory bulb, and cortex and disperse into many brain regions in E18-20. No 5-HTT-im cell bodies were seen in nigral, locus ceruleus, or hypothalamus. However, the transient expression of 5-HTT on non-serotonergic system was seen in cortical and striatal neuroepithelia at E12 and sensory thalamic pathways at P0-P10. Prominent 5-HTT-im fibers in thalamocortical bundles project from sensory thalamic nuclei through reticular nucleus, internal capsule bundle and form barrels in somatosensory cortices. No 5-HTT-im was seen in glia-like cells using currently available antibody. These observations indicate that 5-HTT is: (a) associated preferentially with 5-HT neurons in brainstem, (b) temporally co-expressed with 5-HT in 5-HT neurons, (c) expressed on axons prior to synaptical sites at target neurons, which strongly indicates a volumic (extrasynaptic) transmission, (d) expressed in non-5-HT neurons within a specific window, which may affect the development of the systems "borrowing" the 5-HT. The early appearance of 5-HTT may also endow functionality as well as vulnerabilities of 5-HT, sensory thalamic, and cortical neurons to 5-HTT targeting drugs during pregnancy and after birth.
Zhou
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Department of Anatomy, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN 46202, USA. imce100@iupui.edu
Sari
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Zhang
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D000818:Animals; D001369:Axons / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D001931:Brain Mapping; D002352:Carrier Proteins / Q000096:biosynthesis*; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism; D005865:Gestational Age; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D026901:Membrane Transport Proteins; D009412:Nerve Fibers / Q000378:metabolism; D009419:Nerve Tissue Proteins; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009928:Organ Specificity; D012333:RNA, Messenger / Q000096:biosynthesis*; D011903:Raphe Nuclei / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins; D013788:Thalamus / Q000166:cytology / Q000196:embryology / Q000378:metabolism
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; D012701:Serotonin