Survival and mitogenesis of neuroepithelial cells are influenced by noradrenergic but not cholinergic innervation in cultured embryonic rat neopallium

Popovik, Elvira; Haynes, Laurence W.

doi:10.1016/s0006-8993(99)02242-8

Cited by 43 publications

(32 citation statements)

References 38 publications

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“…A postulated role for AChE in neurite formation does not entail effects that would be exclusive to ACh neurons, so we would therefore expect a dichotomy in the impact on the two markers. Further, effects of neonatal 6-OHDA lesioning on ChAT can provide corroborating evidence for a specific trophic role of norepinephrine itself in forebrain assembly, as postulated in earlier work [19,30,39,41]. Finally, we examined sex differences in the response to neonatal 6-OHDA lesioning.…”

Section: Introductionsupporting

confidence: 78%

Nonenzymatic role of acetylcholinesterase in neuritic sprouting: Regional changes in acetylcholinesterase and choline acetyltransferase after neonatal 6-hydroxydopamine lesions

Slotkin

Ryde

Wrench

et al. 2009

Neurotoxicology and Teratology

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Acetylcholinesterase (AChE) is postulated to play a nonenzymatic role in the development of neuritic projections. We gave the specific neurotoxin, 6-OHDA to rats on postnatal day (PN) 1, a treatment that destroys noradrenergic nerve terminals in the forebrain while producing reactive sprouting in the brainstem. AChE showed profound decreases in the forebrain that persisted in males over the entire phase of major synaptogenesis, from PN4 through PN21; in the brainstem, AChE was increased. Parallel examinations of choline acetyltransferase, an enzymatic marker for cholinergic nerve terminals, showed a different pattern of 6-OHDA-induced alterations, with initial decreases in both forebrain and brainstem in males and regression toward normal by PN21; females were far less affected. The sex differences are in accord with the greater plasticity of the female brain and its more rapid recovery from neurotoxic injury; our findings indicate that these differences are present well before puberty. These results support the view that AChE is involved in neurite formation, unrelated to its enzymatic role in cholinergic neurotransmission. Further, the results for choline acetyltransferase indicate that early depletion of norepinephrine compromises development of acetylcholine systems, consistent with a trophic role for this neurotransmitter.

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Section: Introductionsupporting

confidence: 78%

Nonenzymatic role of acetylcholinesterase in neuritic sprouting: Regional changes in acetylcholinesterase and choline acetyltransferase after neonatal 6-hydroxydopamine lesions

Slotkin

Ryde

Wrench

et al. 2009

Neurotoxicology and Teratology

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“…In either case, the sexselective effects of Dex on adrenergic receptors and corresponding cell signaling during this critical period are likely to contribute to long-term effects. Both a 2 ARs and bARs exert direct control over neural cell replication and apoptotic cell elimination as required for architectural assembly of the brain (Duncan et al, 1990;Garofolo et al, 2003;Kreider et al, 2004;Lidow and Rakic, 1995;Popovik and Haynes, 2000;Slotkin et al, 1988;Zhu et al, 1998). Glucocorticoid effects on adrenergic receptor expression and signaling may thus provide a contributory mechanism to the sex-selectivity seen for the ultimate behavioral outcomes (Bowman et al, 2004;Kreider et al, 2005).…”

Section: Discussionmentioning

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

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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.

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“…Other adrenoceptors may also play a role, however. Postsynaptic alpha1-adrenoceptors were also reported to have antiapoptotic activity in some cellular systems (Popovik and Haynes, 2000). The role of postsynaptic beta-adrenoceptors has not been evaluated.…”

Section: What Mechanism Underlies the Effects Of Dexefaroxan On The Smentioning

confidence: 99%

The Alpha2-Adrenoceptor Antagonist Dexefaroxan Enhances Hippocampal Neurogenesis by Increasing the Survival and Differentiation of New Granule Cells

Rizk

Salazar

Raisman‐Vozari

et al. 2005

Neuropsychopharmacol

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The generation of new neurons in the hippocampus is a dynamic process regulated by environmental, endocrine, and pharmacological factors. Since enhancement of hippocampal neurogenesis has been associated with learning and memory, and the locus coeruleusnoradrenergic system has been shown to modulate these cognitive functions, we hypothesized that activation of noradrenergic neurotransmission might enhance neurogenesis in the adult hippocampus. To test this hypothesis in vivo, we induced the release of noradrenaline in the hippocampus by blocking presynaptic inhibitory autoreceptors with the selective alpha2-adrenoceptor antagonist dexefaroxan. Confocal microscopy showed that noradrenergic afferents make contact with proliferating and differentiating cells, suggesting a direct noradrenergic influence on neurogenesis. Chronic systemic treatment of rats with dexefaroxan did not affect cell proliferation per se in the dentate gyrus (as monitored by bromodeoxyuridine-labeling), but promoted the long-term survival of newborn neurons by reducing apoptosis. Dexefaroxan treatment also enhanced the number and complexity of the dendritic arborizations of polysialated neural cell adhesion molecule-positive neurons. The trophic effects of dexefaroxan on newborn cells might involve an increase in brain-derived neurotrophic factor, which was upregulated in afferent noradrenergic fiber projection areas and in neurons in the granule cell layer. By promoting the survival of new endogenously formed neurons, dexefaroxan treatment represents a potential therapeutic strategy for maintaining adult neurogenesis in neurodegenerative conditions, such as Alzheimer's disease, that affect the hippocampus.

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Survival and mitogenesis of neuroepithelial cells are influenced by noradrenergic but not cholinergic innervation in cultured embryonic rat neopallium

Cited by 43 publications

References 38 publications

Nonenzymatic role of acetylcholinesterase in neuritic sprouting: Regional changes in acetylcholinesterase and choline acetyltransferase after neonatal 6-hydroxydopamine lesions

Nonenzymatic role of acetylcholinesterase in neuritic sprouting: Regional changes in acetylcholinesterase and choline acetyltransferase after neonatal 6-hydroxydopamine lesions

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

The Alpha2-Adrenoceptor Antagonist Dexefaroxan Enhances Hippocampal Neurogenesis by Increasing the Survival and Differentiation of New Granule Cells

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