Serotonin as a Differentiation Signal in Early Neurogenesis

Lauder, Jean M.; Krebs, Helmut

doi:10.1159/000112549

Cited by 441 publications

(172 citation statements)

References 30 publications

Supporting

Mentioning

161

Contrasting

Unclassified

Order By: Relevance

“…It should be noted that other pharmacological and genetic manipulations of the embryonic serotonergic system are available, such as blocking embryonic 5-HT synthesis with p-chlorophenylalanine (pCPA) (Lauder and Krebs, 1978;Lauder et al, 1985), or knocking out genes that are necessary for the development of serotonergic neurons (Hendricks et al, 2003) or serotonergic cortical projections (Donovan et al, 2002). However, prenatal treatment with 5-MT has the following advantages: (1) 5-MT is endogeneously present in the brain (Patel et al, 1986); (2) its effect on cortical serotonergic fibers is transient and gradually disappears postnatally (Shemer et al, 1991); (3) the injections are easy to make, and treated mice deliver without the delay observed in pCPA-treated animals (Lauder and Krebs, 1978); (4) it mimics the elevated levels of blood 5-HT in autism and produces rat pups that have some "autistic-like" symptoms (Kahne et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Early Serotonergic Projections to Cajal-Retzius Cells: Relevance for Cortical Development

Janušonis¹,

Glunčić²,

Rakić³

2004

J. Neurosci.

135

123

View full text Add to dashboard Cite

Although the serotonergic system plays an important role in various neurological disorders, the role of early serotonergic projections to the developing cerebral cortex is not well understood. Because serotonergic fibers enter the marginal zone (MZ) before birth, it has been suggested that they may influence cortical development through synaptic contacts with Cajal-Retzius (CR) cells. We used immunohistochemistry combined with confocal and electron microscopy to show that the earliest serotonergic projections to the MZ form synaptic contacts with the somata and proximal dendrites of CR cells as early as embryonic day 17. To elucidate the functional significance of these early serotonergic contacts with CR cells, we perturbed their normal development by injecting pregnant mice with 5-methoxytryptamine. Lower reelin levels were detected in the brains of newborn pups from the exposed animals. Because reelin plays an important role in the cortical laminar and columnar organization during development, we killed some pups from the same litters on postnatal day 7 and analyzed their presubicular cortex. We found that the supragranular layers of the presubicular cortex (which normally display a visible columnar deployment of neurons) were altered in the treated animals. Our results suggest a mechanism of how serotonergic abnormalities during cortical development may disturb the normal cortical organization; and, therefore, may be relevant for understanding neurological disorders in which abnormalities of the serotonergic system are accompanied by cortical pathology (such as autism).

show abstract

Section: Discussionmentioning

confidence: 99%

Early Serotonergic Projections to Cajal-Retzius Cells: Relevance for Cortical Development

Janušonis¹,

Glunčić²,

Rakić³

2004

J. Neurosci.

135

123

View full text Add to dashboard Cite

show abstract

“…Appropriate stimulation during a critical period of development is necessary for normal maturation, while inappropriate stimulation during these transitions causes abnormal development [227]. For example, dopamine [70,107,125,203,216] and serotonin [123,126,228] have trophic roles early in development (including neuroblast division, cell migration, and synapse formation). Dopamine increases neuronal branching and outgrowth [216] via the D2 receptor family [202].…”

Section: Neurotransmitters Themselves Serve Trophic Functions In the mentioning

confidence: 99%

Trajectories of brain development: point of vulnerability or window of opportunity?

Andersen

2003

Neuroscience & Biobehavioral Reviews

1,325

1,006

View full text Add to dashboard Cite

Brain development is a remarkable process. Progenitor cells are born, differentiate, and migrate to their final locations. Axons and dendrites branch and form important synaptic connections that set the stage for encoding information potentially for the rest of life. In the mammalian brain, synapses and receptors within most regions are overproduced and eliminated by as much as 50% during two phases of life: immediately before birth and during the transitions from childhood, adolescence, to adulthood. This process results in different critical and sensitive periods of brain development. Since Hebb (1949) first postulated that the strengthening of synaptic elements occurs through functional validation, researchers have applied this approach to understanding the sculpting of the immature brain. In this manner, the brain becomes wired to match the needs of the environment. Extensions of this hypothesis posit that exposure to both positive and negative elements before adolescence can imprint on the final adult topography in a manner that differs from exposure to the same elements after adolescence. This review endeavors to provide an overview of key components of mammalian brain development while simultaneously providing a framework for how perturbations during these changes uniquely impinge on the final outcome. q

show abstract

“…Furthermore, it suggests that blockade of 5-HT 2 receptors at these ages may be useful Prenatal Opiate Withdrawal and Serotonin 2 Receptors therapeutically in situations where excess 5-HT activity is deleterious. However, it is important to note that 5-HT plays multiple roles in the developing nervous system, including acting as a growth and trophic factor during early stages of development (e.g., Lauder and Krebs, 1978). Thus, disruption of 5-HT signaling via receptor blockade, even in the presence of excess 5-HT activity, may have deleterious consequences during certain stages of development (Schrott et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Prenatal Opiate Withdrawal Activates the Chick Embryo Hypothalamic-Pituitary-Adrenal Axis and Dilates Vitelline Blood Vessels via Serotonin₂ Receptors

Schrott¹,

Baumgart²,

Zhang³

et al. 2002

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Opiate withdrawal during pregnancy may occur because of voluntary or forced detoxification, or from rapid cycling associated with exposure to short-acting "street" opiates. Thus, animal modeling of prenatal withdrawal and development of potential therapeutic interventions is important. Direct developmental effects of opiates and/or withdrawal can be studied using a chick model. In ovo administration of the long-acting opiate N-desmethyl-l-␣-noracetylmethadol (NLAAM) induces opiate dependence in the chick embryo. We examined activation of the hypothalamic-pituitary-adrenal (HPA) axis (assessed via serum corticosterone) and hemodynamic changes (assessed as changes in apparent diameter of vitelline (extraembryonic) blood vessels) after chronic NLAAM exposure and naloxone (Nx)-precipitated withdrawal during late stages of embryogenesis. Nx-precipitated withdrawal increased corticosterone 2-to 4.5-fold and diameters of vitelline blood vessels by 15 to 45%. NLAAM exposure itself did not effect these measures. In a second set of experiments, isobutylmethylxanthine (IBMX), a phosphodiesterase inhibitor, was injected into eggs with embryos. IBMX similarly increased corticosterone and vitelline vessel diameter, with a similar time course and response magnitude. Previous studies found that serotonin 2 (5-HT 2 ) receptors were involved in other withdrawal manifestations, so we determined whether they were likewise involved. Pretreatment with the 5-HT 2 antagonist ritanserin completely blocked HPA axis activation and vasodilation associated with both Nx-precipitated withdrawal and IBMX administration. This indicates that 5-HT 2 receptors, directly or indirectly, mediate these withdrawal manifestations in the chick embryo.

show abstract

Serotonin as a Differentiation Signal in Early Neurogenesis

Cited by 441 publications

References 30 publications

Early Serotonergic Projections to Cajal-Retzius Cells: Relevance for Cortical Development

Early Serotonergic Projections to Cajal-Retzius Cells: Relevance for Cortical Development

Trajectories of brain development: point of vulnerability or window of opportunity?

Prenatal Opiate Withdrawal Activates the Chick Embryo Hypothalamic-Pituitary-Adrenal Axis and Dilates Vitelline Blood Vessels via Serotonin₂ Receptors

Contact Info

Product

Resources

About

Serotonin as a Differentiation Signal in Early Neurogenesis

Cited by 441 publications

References 30 publications

Early Serotonergic Projections to Cajal-Retzius Cells: Relevance for Cortical Development

Early Serotonergic Projections to Cajal-Retzius Cells: Relevance for Cortical Development

Trajectories of brain development: point of vulnerability or window of opportunity?

Prenatal Opiate Withdrawal Activates the Chick Embryo Hypothalamic-Pituitary-Adrenal Axis and Dilates Vitelline Blood Vessels via Serotonin2 Receptors

Contact Info

Product

Resources

About

Prenatal Opiate Withdrawal Activates the Chick Embryo Hypothalamic-Pituitary-Adrenal Axis and Dilates Vitelline Blood Vessels via Serotonin₂ Receptors