Neuroscience 1998 Apr;83(4):1185-1201

Serotonin transporter messenger RNA in the developing rat brain: early
expression in serotonergic neurons and transient expression in
non-serotonergic neurons.

Hansson SR, Mezey E, Hoffman BJ

Unit on Molecular Pharmacology, Laboratory of Cellular and Molecular
Regulation, National Institute of Mental Health,
Bethesda, MD 20892, USA.

Serotonin has been shown to affect the development of the mammalian
nervous system. The serotonin transporter is a major
factor in regulating extracellular serotonin levels. Using in situ
hybridization histochemistry the rat serotonin transporter
messenger RNA was localized during embryogenesis, the first four weeks
postnatally and adulthood. Three general classes
of serotonin transporter messenger RNA expression patterns were
observed: (i) early detection with continued expression
through adult age, (ii) transient expression colocalized with vesicular
monoamine transporter 2 messenger RNA but with no
detectable tryptophan hydroxylase immunoreactivity, and (iii) transient
expression in the apparent absence of both vesicular
monoamine transporter 2 messenger RNA and tryptophan hydroxylase
immunoreactivity. For example, hybridization for
serotonin transporter messenger RNA was strong in serotonin cell
body-containing areas beginning early in gestation, and
remained intense through adulthood. Immunoreactivity for tryptophan
hydroxylase, the rate-limiting enzyme in serotonin
synthesis, was completely overlapping with the presence of serotonin
transporter messenger RNA in raphe nuclei
postnatally. Sensory relay systems including the ventrobasal nucleus
(somatosensory), lateral and medial geniculate nuclei
(visual and auditory, respectively) as well as trigeminal, cochlear and
solitary nuclei were representative of the second class
of observations. In general, the limbic system expressed serotonin
transporter messenger RNA in the third pattern with
various limbic structures differing in the timing of expression. Septum,
olfactory areas and the developing hippocampus
contained serotonin transporter messenger RNA early in the developing
brain. Other regions such as cingulate and
frontopolar cortex exhibited hybridization peri- and postnatally,
respectively. Several hypothalamic nuclei and pituitary
transiently expressed serotonin transporter messenger RNA either
postnatally or perinatally, respectively. If the observed
patterns correlate with functional protein expression, distinct classes
of serotonin transporter messenger RNA expression
may reflect different functional roles for the serotonin transporter and
serotonin, itself. Since the serotonin transporter is a
target for a number of addictive substances including cocaine and
amphetamine derivatives as well as antidepressants,
transient expression of the serotonin transporter might suggest a window
of vulnerability of associated cells to fetal drug
exposure. Re-uptake, storage and re-release from non-serotonergic
neurons might serve as a feedback mechanism from
target neurons to serotonergic neurons. Alternatively, the transient
expression of serotonin transporter messenger RNA may
reflect critical periods important for tight regulation of extracellular
serotonin in several brain regions, and may indicate
previously unappreciated roles for serotonin as a developmental cue.

PMID: 9502257, UI: 98161362