J M Lauder — Page 7 | Search PubMed

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In utero exposure to serotonergic drugs alters neonatal expression of 5-HT(1A) receptor transcripts: a quantitative RT-PCR study.

In embryonic rat brain, serotonin (5-HT) acts as a differentiation signal for 5-HT neurons and their target cells during midgestation. Serotonin receptors expressed during this period include the 5-HT(1A) subtype, which may mediate some of these developmental effects. Using the highly sensitive method of competitive RT-PCR, we quantified the effects of maternal treatment with either p-chlorophenylalanine (pCPA; which depletes 5-HT in embryonic rat brain) or 5-methoxytryptamine (5-MT; a general 5-HT(1) /5-HT(2) agonist) from embryonic day E12-17 on expression of 5-HT(1A) receptor mRNA transcripts in brains of offspring at postnatal day 4 (PND 4). In offspring of both pCPA and 5-MT treated mothers, 5-HT(1A) transcripts were significantly reduced compared to vehicle controls, although effects of pCPA were greater than those of 5-MT. These results indicate that either under-stimulation of 5-HT(1A) receptors (due to pCPA-induced 5-HT depletion) or over-stimulation (by the agonist 5-MT) during prenatal development significantly reduced expression of 5-HT(1A) receptor transcripts in neonatal offspring. This may occur by disruption of 5-HT(1A) gene transcription or by post-transcriptional mechanisms (such as altered translation or turnover of mRNA). Whatever the mechanism, reductions in 5-HT(1A) receptor transcripts following in utero exposure to serotonergic drugs could significantly impact the number of 5-HT(1A) receptors expressed in neonatal rat brain. Whether such effects will persist into adulthood remains to be determined.

5-Methoxytryptamine↗

PubMedDate not supplied

Postnatal expression of the serotonin transporter in auditory brainstem neurons.

To investigate the putative role of serotonin (5-HT) in auditory brainstem development, the expression of the 5-HT transporter (5-HTT) was evaluated in the normal mouse brainstem at 6 different postnatal ages. The brains of C3H/HeJ mice at birth (P0) and P1, P8-P9, P13, P21-P22, P35-P36 and P48-P50 were collected and processed immunohistochemically with an antibody raised against the 5-HTT. 5-HTT immunoreactivity (5-HTT-IR) was first observed in P8 mice and was localized to cell bodies in the ventral cochlear nucleus (VCN) and principal nuclei of the superior olivary complex, including the medial nucleus of the trapezoid body. Labeled neurons were found in similar regions in older mice except at P48-50, where labeled neurons were observed in the VCN only. 5-HTT-IR was especially prominent in VCN neurons at P21 and was observed in all of the brains examined at this age. These results indicate that auditory brainstem neurons of the normal inbred mouse express the 5-HTT postnatally. The presence of 5-HTT-IR in neurons located in the VCN indicates a regional expression of the 5-HTT that is related to the ascending auditory pathway. The timing of 5-HTT expression indicates that 5-HT may modulate developmental processes that rely on cochlear input.

Aging↗