Developmental Increase (developmental + increase)

Distribution by Scientific Domains

Selected Abstracts

Neural agrin increases postsynaptic ACh receptor packing by elevating rapsyn protein at the mouse neuromuscular synapse

Jennifer Brockhausen
Abstract Fluorescence resonance energy transfer (FRET) experiments at neuromuscular junctions in the mouse tibialis anterior muscle show that postsynaptic acetylcholine receptors (AChRs) become more tightly packed during the first month of postnatal development. Here, we report that the packing of AChRs into postsynaptic aggregates was reduced in 4-week postnatal mice that had reduced amounts of the AChR-associated protein, rapsyn, in the postsynaptic membrane (rapsyn+/, mice). We hypothesize that nerve-derived agrin increases postsynaptic expression and targeting of rapsyn, which then drives the developmental increase in AChR packing. Neural agrin treatment elevated the expression of rapsyn in C2 myotubes by a mechanism that involved slowing of rapsyn protein degradation. Similarly, exposure of synapses in postnatal muscle to exogenous agrin increased rapsyn protein levels and elevated the intensity of anti-rapsyn immunofluorescence, relative to AChR, in the postsynaptic membrane. This increase in the rapsyn-to-AChR immunofluorescence ratio was associated with tighter postsynaptic AChR packing and slowed AChR turnover. Acute blockade of synaptic AChRs with ,-bungarotoxin lowered the rapsyn-to-AChR immunofluorescence ratio, suggesting that AChR signaling also helps regulate the assembly of extra rapsyn in the postsynaptic membrane. The results suggest that at the postnatal neuromuscular synapse agrin signaling elevates the expression and targeting of rapsyn to the postsynaptic membrane, thereby packing more AChRs into stable, functionally-important AChR aggregates. 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008 [source]

GluR- and TrkB-mediated maturation of GABAA receptor function during the period of eye opening

Christian Henneberger
Abstract Synapse maturation includes the shortening of postsynaptic currents, due to changes in the subunit composition of respective transmitter receptors. Patch clamp experiments revealed that GABAergic inhibitory postsynaptic currents (ISPCs) of superior colliculus neurons significantly shorten from postnatal day (P)1 to P21. The change started after P6 and was steepest between P12 and P15, i.e. around eye opening. It was accompanied by enhanced sensitivity to zolpidem and increased expression of GABAAR ,1 mRNA, whereas the level of ,3 mRNA decreased. This result is consistent with the hypothesis that the IPSC kinetics of developing collicular neurons is determined by the level of ,1/,3. As ,1/,3 peaked when N -methyl-D-aspartate receptor (NMDAR)-mediated synaptic currents reached their maximum (P12) it was asked whether NMDAR activity can shape the kinetics of GABAergic IPSCs. Cultured collicular neurons were treated with NMDA or NMDAR block, and it was found that the former resulted in faster and the latter in slower IPSC decay. Group I mGluR blockade had no effect. Experiments with bdnf,/, mice revealed that, with some delay, the increase of ,1/,3 mRNA also occurred in the chronic absence of brain-derived neurotrophic factor (BDNF) and, again, this was accompanied by the shortening of IPSCs. In addition, there was an age-dependent depression of IPSC amplitudes by endogenous BDNF, which might reflect the developmental increase in the expression of GABAAR ,2L, as opposed to ,2S. Together, these experiments suggest that the GABAAR , subunit switch and the associated change in the IPSC kinetics were specifically controlled by NMDAR activity and independent on the signalling through group I mGluRs or TrkB. [source]

Developmental and environmental regulation of antifreeze proteins in the mealworm beetle Tenebrio molitor

FEBS JOURNAL, Issue 21 2000
Laurie A. Graham
The yellow mealworm beetle, Tenebrio molitor, contains a family of small Cys-rich and Thr-rich thermal hysteresis proteins that depress the hemolymph freezing point below the melting point by as much as 5.5 C (,T = thermal hysteresis). Thermal hysteresis protein expression was evaluated throughout development and after exposure to altered environmental conditions. Under favorable growth conditions, small larvae (11,13 mg) had only low levels of thermal hysteresis proteins or thermal hysteresis protein message, but these levels increased 10-fold and 18-fold, respectively, by the final larval instar (> 190 mg), resulting in thermal hysteresis >,3 C. Exposure of small larvae (11,13 mg) to 4 weeks of cold (4 C) caused an ,,20-fold increase in thermal hysteresis protein concentration, well in excess of the less than threefold developmental increase seen after 4 weeks at 22 C. Exposure of large larvae (100,120 mg) to cold caused 12-fold and sixfold increases in thermal hysteresis protein message and protein levels, respectively, approximately double the maximum levels they would have attained in the final larval instar at 22 C. Thus, thermal hysteresis increased to similar levels (> 4 C) in the cold, irrespective of the size of the larvae (the overwintering stage). At pupation, thermal hysteresis protein message levels decreased >,20-fold and remained low thereafter, but thermal hysteresis activity decreased much more slowly. Exposure to cold did not reverse this decline. Desiccation or starvation of larvae had comparable effects to cold exposure, but surprisingly, short daylength photoperiod or total darkness had no effect on either thermal hysteresis or message levels. As all environmental conditions that caused increased thermal hysteresis also inhibited growth, we postulate that developmental arrest is a primary factor in the regulation of T. molitor thermal hysteresis proteins. [source]

Oxygen resuscitation does not ameliorate neonatal hypoxia/ischemia-induced cerebral edema

Diana Carolina Ferrari
Abstract Neonatal hypoxia/ischemia (HI) is a common cause of cognitive and behavioral deficits in children with hyperoxia treatment (HHI) being the current therapy for newborn resuscitation. HI induces cerebral edema that is associated with poor neurological outcomes. Our objective was to characterize cerebral edema after HI and determine the consequences of HHI (40% or 100% O2). Dry weight analyses showed cerebral edema 1 to 21 days after HI in the ipsilateral cortex; and 3 to 21 days after HI in the contralateral cortex. Furthermore, HI increased blood-brain barrier (BBB) permeability 1 to 7 days after HI, leading to bilateral cortical vasogenic edema. HHI failed to prevent HI-induced increase in BBB permeability and edema development. At the molecular level, HI increased ipsilateral, but not contralateral, AQP4 cortical levels at 3 and up to 21 days after HI. HHI treatment did not further affect HI-induced changes in AQP4. In addition, we observed developmental increases of AQP4 accompanied by significant reduction in water content and increase permeability of the BBB. Our results suggest that the ipsilateral HI-induced increase in AQP4 may be beneficial and that its absence in the contralateral cortex may account for edema formation after HI. Finally, we showed that HI induced impaired motor coordination 21 days after the insult and HHI did not ameliorate this behavioral outcome. We conclude that HHI treatment is effective as a resuscitating therapy, but does not ameliorate HI-induced cerebral edema and impaired motor coordination. 2010 Wiley-Liss, Inc. [source]