Dopamine receptors mediate differential morphological effects on cerebral cortical neurons in vitro

Abstract

A morphogenic role of neurotransmitters during cellular differentiation in vitro has been demonstrated in recent years. Using in situ hybridization, we confirm the presence of the D1 receptor at E16 and show additionally that the transcript is relatively widespread and present in both proliferative and differentiating areas of the cerebral wall. Because DA receptor expression precedes the arrival of presynaptic terminals during forebrain development, we examined the role of DA in cerebral cortical neuron differentiation in vitro, using immunohistochemical markers of dendrites, microtubule‐associated‐membrane protein 2 (MAP2) and axons, neurofilament protein (NF‐H). Neurite length, cell size, and cell viability in response to D1 and D2 receptor agonists SKF38393 and quinpirole, respectively, and to DA were analyzed in neurons obtained from embryonic (E) day 16 rats. We have shown that 1) paradoxically, DA at different concentrations can either stimulate or inhibit neurite outgrowth; 2) there is a bimodal pattern of DA‐induced axonal outgrowth, i.e., at low and high doses; 3) D2 receptor activation induces neurite outgrowth while D1 receptor activation is inhibitory; 4) D2‐mediated neurite elongation is preferentially axonal while D1 receptor activation reduces both axonal and dendritic outgrowth; 5) low doses of DA promote the expression of cytoskeletal components of axonal maturation; and 6) D1 receptor activation decreases neuronal size. We suggest that DA may influence cellular differentiation and circuitry formation early in development of the cerebral cortex through receptor‐mediated effects on process outgrowth, which could lead to effects on circuit formation. © 1996 Wiley‐Liss, Inc.

Caesarean Section Birth Produces Long Term Changes in Dopamine D1 Receptors and in Stress-induced Regulation of D3 and D4 Receptors in the Rat Brain

“…C-section may alter the normal developmental trajectory of D1-like receptors, which are present in rat brain at birth and increase progressively until adulthood (Murrin and Zeng 1990). This could further impact CNS development as D1 receptor activation decreases axonal and dendritic outgrowth in immature neurons (Reinoso et al 1996). Another mechanistic issue is whether increased D1-like receptor binding after C-section represents receptor upregulation in response to altered dopaminergic input.…”

Prenatal Exposure to Cocaine Produces Unique Developmental and Long-Term Adaptive Changes in Dopamine D1Receptor Activity and Subcellular Distribution

“…Primary neuronal cultures were prepared from the presumptive MFC, visual cortex, and striatum of salineand cocaine-exposed rabbit embryos at E22 using slight modifications of published methods (Reinoso et al, 1996;Jones et al, 2000). This corresponds to the latter period of neurogenesis in the rabbit (Stensaas, 1967a,b).…”

“…In the prenatal cocaine model, D 1 receptors appear to be expressed at normal levels but are constitutively hyperphosphorylated (Zhen et al, 2001). D 1 receptor activation modulates neurite outgrowth in a cell context-dependent manner (Reinoso et al, 1996;Schmidt et al, 1996Schmidt et al, , 1998. Here, we examined the differential impact of prenatal cocaine exposure on cortical and striatal neuronal growth and tested the hypothesis that altered growth properties may be attributable to reduced D 1 receptor coupling that is caused by the altered subcellular distribution of the receptor, thus preventing normal coupling.…”

Heterotrimeric G Proteins and the Regulation of Microtubule Assembly

“…The Rho and Ras families of small GTPases have also emerged as critical players in regulating the actin and MT cytoskeleton by modulating downstream effectors, including serine/threonine kinase, p21-activated kinase, ROCK, and mDia [81,82]. GPCRs, as well as α and βγ subunits of heterotrimeric G proteins, have also been shown to regulate neurite outgrowth [83][84][85][86][87][88][89][90]. These studies collectively suggested the role of α and βγ subunits of G proteins in regulating neurite outgrowth.…”