Effect of central nervous system acting drugs on brain cell replication in vitro

Abstract

The role in the regulation of cell replication of the neurotransmitter compounds and the drugs which affect their balance was studied in vitro, using morphologically preserved brain slices. Compounds affecting noradrenergic, dopaminergic and serotoninergic neurotransmitter systems reduced the brain cell replication, measured in terms of the rate of [3H]thymidine incorporation into DNA. The reduction was dose dependent and half-maximal effects were obtained at about 1-5 x 10(-4) M concentrations. Although agonists and antagonists both showed similar inhibitory effect, the action of agonists was reversed by the appropriate antagonists. Also, the pharmacologically active isomers were several-fold more effective than the inactive isomers in forebrain slices, although with cerebellar slices the selectivity was less marked. Cyclic nucleotides and drugs affecting cholinergic neurotransmitter systems were apparently ineffective. These results indicate that monoamines may be involved in the regulation of cell replication in the developing brain. Furthermore, as some of the CNS acting drugs tested are suspected behavioural teratogens the present results suggest that the reported behavioural abnormalities in the offspring may be related, in part, to a chronologically determined interference with the formation of certain cell types.

Regulation of fetal cardiac and hepatic β-adrenoceptors and adenylyl cyclase signaling: terbutaline effects

“…Cardiac anomalies, including apoptosis, have indeed been noted after fetal Ter treatment (20,28). Equally important, the developing brain exhibits the same trophic role for ␤-adrenergic input in the control of cell replication and differentiation (1,9,14,18,21,25,40,44) and thus is likely to provide a similar target for adverse effects of prenatal Ter treatment. Although only a few papers have appeared on this topic (11,25,32,38), they all point toward Ter-induced disruption of cell differentiation and synaptic function.…”

Concurrent cellular output from two proliferative populations in the early embryonic mouse corpus striatum

“…Dopaminergic inputs from the ventral mesencephalon arrive in the ganglionic eminence by E11 in mice (Golden, 1973;our unpublished observations). Dopamine is known to influence cell proliferation (Barochovsky and Patel, 1982;Gary and Chronwall, 1992;Lajiness et al, 1993). A variety of genes is expressed within the embryonic nervous system in a region-specific manner (Stern and Keynes, 1988;Keynes and Lumsden, 1990;Puelles and Rubenstein, 1993).…”

A Method for the Detection of Meaningful and Reproducible Group Signatures From Gene Expression Profiles

“…Barochovsky et al have demonstrated in vivo that compounds acting on the central nervous system, specifically those that affect noradrenergic, dopaminergic, and serotoninergic neurotransmitters, reduce brain cell replication. 35 This observation of compounds acting on the CNS was a dose-dependent effect and was seen for both agonists and antagonists. This down-expressed signature, like the up-expressed signature, is well supported by the literature.…”