β-adrenergic receptors regulate astrogliosis and cell proliferation in the central nervous system in vivo

Hodges-Savola, Cheryl; Rogers, Scott D.; Ghilardi, Joseph R.; Timm, David R.; Mantyh, Patrick W.

doi:10.1002/(sici)1098-1136(199605)17:1<52::aid-glia5>3.0.co;2-9

Cited by 58 publications

(22 citation statements)

References 46 publications

(48 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although we did not perform dose-response or antagonist studies to provide definitive demonstration that the effects are mediated through ␤ 2 ARs within the developing brain, the fact that the pattern of alterations mirrors the regional and temporal distribution of the receptors, incorporates the known consequences of ␤AR overstimulation on cell replication and cell death, and parallels the effects of terbutaline on cell signaling all point to a receptor-mediated origin (Joseph et al, 1983;Lorton et al, 1988;Erdtsieck-Ernste et al, 1991;Teerlink et al, 1994;Hodges-Savola et al, 1996;Communal et al, 1998;Shizukuda et al, 1998;Gu et al, 2000;Yan et al, 2000;Singh et al, 2001;Slotkin et al, 2001Slotkin et al, , 2003Garofolo et al, 2003). Using neuroprotein biomarkers for astroglia (GFAP) and proximal neuronal projections (NF68), we obtained patterns that are typical of neuronal damage and reactive gliosis: initial increases in GFAP that eventually resolve and are replaced by elevated NF68, which is associated with reactive sprouting in response to injury (O'Callaghan, 1988;Schroeder et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

“…␤ARs are prominently expressed on both developing neurons and glia (Lorton et al, 1988;Hodges-Savola et al, 1996), so that terbutaline is likely to target either cell type. Accordingly, we conducted quantitative morphometric studies in the cerebellum, hippocampus, and somatosensory cortex after exposure of neonatal rats to terbutaline in two developmental periods, postnatal days PN2 to 5 and PN11 to 14.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Terbutaline Is a Developmental Neurotoxicant: Effects on Neuroproteins and Morphology in Cerebellum, Hippocampus, and Somatosensory Cortex

Rhodes

Seidler²,

Abdel-Rahman³

et al. 2003

J Pharmacol Exp Ther

View full text Add to dashboard Cite

␤ 2 -Adrenoceptor agonists, especially terbutaline, are widely used to arrest preterm labor, but they also cross the placenta to stimulate fetal ␤-adrenoceptors that control neural cell differentiation. We evaluated the effects of terbutaline administration in neonatal rats, a stage of neurodevelopment corresponding to human fetal development. Terbutaline administered on postnatal days PN2 to 5 elicited neurochemical changes indicative of neuronal injury and reactive gliosis: immediate increases in glial fibrillary acidic protein and subsequent induction of the 68-kDa neurofilament protein. Quantitative morphological evaluations carried out on PN30 indicated structural abnormalities in the cerebellum, hippocampus, and somatosensory cortex. In the cerebellum, PN2 to 5 terbutaline treatment reduced the number of Purkinje cells and elicited thinning of the granular and molecular layers. The hippocampal CA3 region also displayed thinning, along with marked gliosis, effects that were restricted to females. In the somatosensory cortex, terbutaline evoked a reduction in the proportion of pyramidal cells and an increase in smaller, nonpyramidal cells; again, females were affected more than males. Although abnormalities were obtained with later terbutaline treatment (PN11 to 14), in general the effects were smaller than those seen with PN2 to 5 exposure. Our results indicate that terbutaline is a neurotoxicant that elicits biochemical alterations and structural damage in the immature brain during a critical period. These effects point to a causal relationship between fetal terbutaline exposure and the higher incidence of cognitive and neuropsychiatric disorders reported for the offspring of women receiving terbutaline therapy for preterm labor.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Terbutaline Is a Developmental Neurotoxicant: Effects on Neuroproteins and Morphology in Cerebellum, Hippocampus, and Somatosensory Cortex

Rhodes

Seidler²,

Abdel-Rahman³

et al. 2003

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

“…and Rompun (tiazine⅐HCl, 10 mg͞kg body weight, i.m.). Surgical procedures were as previously described (12). Vehicle and drugs were continuously delivered through a catheter (24G) implanted under the dura mater enwrapping one optic nerve.…”

Section: Methodsmentioning

confidence: 99%

Glutamate receptor-mediated toxicity in optic nerve oligodendrocytes

Matute

Sánchez‐Gómez

Martínez‐Millán

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

328

267

View full text Add to dashboard Cite

In cultured oligodendrocytes isolated from perinatal rat optic nerves, we have analyzed the expression of ionotropic glutamate receptor subunits as well as the effect of the activation of these receptors on oligodendrocyte viability. Reverse transcription-PCR, in combination with immunocytochemistry, demonstrated that most oligodendrocytes differentiated in vitro express the ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits GluR3 and GluR4 and the kainate receptor subunits GluR6, GluR7, KA1 and KA2. Acute and chronic exposure to kainate caused extensive oligodendrocyte death in culture. This effect was partially prevented by the AMPA receptor antagonist GYKI 52466 and was completely abolished by the non-N-methyl-Daspartate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), suggesting that both AMPA and kainate receptors mediate the observed kainate toxicity. Furthermore, chronic application of kainate to optic nerves in vivo resulted in massive oligodendrocyte death which, as in vitro, could be prevented by coinfusion of the toxin with CNQX. These findings suggest that excessive activation of the ionotropic glutamate receptors expressed by oligodendrocytes may act as a negative regulator of the size of this cell population.The main function of oligodendrocytes is to myelinate axons in the vertebrate central nervous system. This cell type develops mostly soon after the majority of neurons are generated and have extended their axons and, therefore, it is likely that neurons play an important role in regulating oligodendrocyte development. In the rat optic nerve, the first fully differentiated oligodendrocytes appear after birth, and the definitive mature population of oligodendrocytes is reached around 6 weeks later (1, 2). The proliferation and the survival of oligodendrocytes depend, respectively, on the electrical activity of neighboring axons and in the reciprocal contacts they establish (for a recent review, see ref.3). Axon to oligodendrocyte signaling results in the generation of the precise number of oligodendrocytes necessary to myelinate entirely a given population of axons. Unfortunately, little information is available about the molecules participating in this signaling process.Oligodendrocytes express neurotransmitter receptors including those activated by glutamate (4). This excitatory amino acid acts at various types of receptors, which can be grouped into two major categories: ionotropic receptors, which gate membrane ion channels permeable to cations; and metabotropic receptors, which are coupled to G proteins. Ionotropic receptors are classified into ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate, and N-methyl-Daspartate (NMDA) subtypes, according to their preferred agonist. Molecular cloning has revealed that each receptor subtype is composed of several subunits with high homology within each receptor class (reviewed in ref. 5). Thus, AMPA receptors are formed by GluR1-4, kainate receptors by GluR5-7 and KA1-2, and NMDA rece...

show abstract

“…We also characterized three neurotransmitter receptor-binding sites, b-adrenoceptor (bAR), a 2 -adrenoceptor (a 2 AR), and m 2 -muscarinic acetylcholine receptor (m 2 AChR). Each receptor has been implicated in the control of neural cell acquisition and differentiation (Duncan et al, 1990;Garofolo et al, 2003;Hodges-Savola et al, 1996;Kreider et al, 2004;Lidow and Rakic, 1995;Slotkin et al, 1988;Zhou et al, 2004) and, like the HC3-binding site, the bAR and a 2 AR are overexpressed in the fetal brain (Kreider et al, 2004;Lidow et al, 1991;Slotkin et al, 1994b;Zahalka et al, 1993a). Notably, glucocorticoids have a direct effect on bAR expression (Davies and Lefkowitz, 1984;Tseng et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Disruption of Rat Forebrain Development by Glucocorticoids: Critical Perinatal Periods for Effects on Neural Cell Acquisition and on Cell Signaling Cascades Mediating Noradrenergic and Cholinergic Neurotransmitter/Neurotrophic Responses

Kreider

Aldridge

Cousins

et al. 2005

Neuropsychopharmacol

View full text Add to dashboard Cite

Glucocorticoids are the consensus treatment for the prevention of respiratory distress in preterm infants, but there is evidence for increased incidence of neurodevelopmental disorders as a result of their administration. We administered dexamethasone (Dex) to developing rats at doses below or within the range of those used clinically, evaluating the effects on forebrain development with exposure in three different stages: gestational days 17-19, postnatal days 1-3, or postnatal days 7-9. At 24 h after the last dose, we evaluated biomarkers of neural cell acquisition and growth, synaptic development, neurotransmitter receptor expression, and synaptic signaling mediated by adenylyl cyclase (AC). Dex impaired the acquisition of neural cells, with a peak effect when given in the immediate postnatal period. In association with this defect, Dex also elicited biphasic effects on cholinergic presynaptic development, promoting synaptic maturation at a dose (0.05 mg/kg) well below those used therapeutically, whereas the effect was diminished or lost when doses were increased to 0.2 or 0.8 mg/kg. Dex given postnatally also disrupted the expression of adrenergic receptors known to participate in neurotrophic modeling of the developing brain and evoked massive induction of AC activity. As a consequence, disparate receptor inputs all produced cyclic AMP overproduction, a likely contributor to disrupted patterns of cell replication, differentiation, and apoptosis. Superimposed on the heterologous AC induction, Dex impaired specific receptor-mediated cholinergic and adrenergic signals. These results indicate that, during a critical developmental period, Dex administration leads to widespread interference with forebrain development, likely contributing to eventual, adverse neurobehavioral outcomes.

show abstract

β-adrenergic receptors regulate astrogliosis and cell proliferation in the central nervous system in vivo

Cited by 58 publications

References 46 publications

Terbutaline Is a Developmental Neurotoxicant: Effects on Neuroproteins and Morphology in Cerebellum, Hippocampus, and Somatosensory Cortex

Terbutaline Is a Developmental Neurotoxicant: Effects on Neuroproteins and Morphology in Cerebellum, Hippocampus, and Somatosensory Cortex

Glutamate receptor-mediated toxicity in optic nerve oligodendrocytes

Disruption of Rat Forebrain Development by Glucocorticoids: Critical Perinatal Periods for Effects on Neural Cell Acquisition and on Cell Signaling Cascades Mediating Noradrenergic and Cholinergic Neurotransmitter/Neurotrophic Responses

Contact Info

Product

Resources

About