The Role of Growth Retardation in Lasting Effects of Neonatal Dexamethasone Treatment on Hippocampal Synaptic Function
Abstract
nullBackground: Dexamethasone (DEX), a synthetic glucocorticoid, is commonly used to prevent or lessen the morbidity of chronic lung disease in preterm infants. However, evidence is now increasing that this clinical practice negatively affects somatic growth and may result in long-lasting neurodevelopmental deficits. We therefore hypothesized that supporting normal somatic growth may overcome the lasting adverse effects of neonatal DEX treatment on hippocampal function.
Methodology/Principal Findings: To test this hypothesis, we developed a rat model using a schedule of tapering doses of DEX similar to that used in premature infants and examined whether the lasting influence of neonatal DEX treatment on hippocampal synaptic plasticity and memory performance are correlated with the deficits in somatic growth. We confirmed that neonatal DEX treatment switched the direction of synaptic plasticity in hippocampal CA1 region, favoring low-frequency stimulation- and group I metabotropic glutamate receptor agonist (S)-3,5,-dihydroxyphenylglycine
Conclusion/Significance: Our results demonstrate that growth retardation plays a crucial role in DEX-induced long-lasting influence of hippocampal function. Our findings suggest that therapeutic strategies designed to support normal development and somatic growth may exert beneficial effects to reduce lasting adverse effects following neonatal DEX treatment.
Citation
PLoS One. 2010 Sep 21; 5(9):e12806Scopus Count
Related items
Showing items related by title, author, creator and subject.
-
Ndel1 Promotes Axon Regeneration via Intermediate FilamentsFailure of axons to regenerate following acute or chronic neuronal injury is attributed to both the inhibitory glial environment and deficient intrinsic ability to re-grow. However, the underlying mechanisms of the latter remain unclear. In this study, we have investigated the role of the mammalian homologue of aspergillus nidulans NudE, Ndel1, emergently viewed as an integrator of the cytoskeleton, in axon regeneration. Ndel1 was synthesized de novo and upregulated in crushed and transected sciatic nerve axons, and, upon injury, was strongly associated with neuronal form of the intermediate filament (IF) Vimentin while dissociating from the mature neuronal IF (Neurofilament) light chain NF-L. Consistent with a role for Ndel1 in the conditioning lesion-induced neurite outgrowth of Dorsal Root Ganglion (DRG) neurons, the long lasting in vivo formation of the neuronal Ndel1/Vimentin complex was associated with robust axon regeneration. Furthermore, local silencing of Ndel1 in transected axons by siRNA severely reduced the extent of regeneration in vivo. Thus, Ndel1 promotes axonal regeneration; activating this endogenous repair mechanism may enhance neuroregeneration during acute and chronic axonal degeneration.
-
The Beeper [1998 Vol. 8, No. 14]Features this week include: MCG's family-centered approach praised; Faculty and staff come first as planning process begins; Stem cell transplant unit celebrates first anniversary; Anticipation builds as move to new CMC approaches; Keep guns away from children; MCG certified to receive gamma knife.
-
The Beeper [1999 Vol. 9, No. 18]Features this week include: Annual SCCC is launched; Campaign under way to "fix" excessive cuts; Access to neurologists enhanced in ACC; The magnolia ball and show scheduled; Mrs. Troiano wins award of excellence; MCG partners with Boys and Girls Club; CMC carnival set for Saturday; Teamwork nets $450,000 cost reduction; Food service director wins award for 'parking lot kitchen'; Q&A: Early retirement; 1,000th pediatric transport reached by service; Lunchtime series focuses on healthy lifestyles; Horse show to benefit Camp Rainbow; E-mail launches German student's visit.
