The Role of Growth Retardation in Lasting Effects of Neonatal Dexamethasone Treatment on Hippocampal Synaptic Function

BACKGROUND: 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-induced long-term depression (LTD), and opposing the induction of long-term potentiation (LTP) by high-frequency stimulation in the adolescent period. The effects of DEX on LTP and LTD were correlated with an increase in the autophosphorylation of Ca(2+)/calmodulin-dependent protein kinase II at threonine-286 and a decrease in the protein phosphatase 1 expression. Neonatal DEX treatment resulted in a disruption of memory retention subjected to object recognition task and passive avoidance learning. The adverse effects of neonatal DEX treatment on hippocampal synaptic plasticity and memory performance of the animals from litters culled to 4 pups were significantly less than those for the 8-pup litters. However, there was no significant difference in maternal care between groups. 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

Measurements of mitochondrial pH in cultured cortical neurons clarify contribution of mitochondrial pore to the mechanism of glutamate-induced delayed Ca2+ deregulation

To clarify the role of the mitochondrial permeability transition pore (MPT) in the mechanism of the glutamate-induced delayed calcium deregulation (DCD) and mitochondrial depolarization (MD), we studied changes in cytosolic (pH(m)) and mitochondrial pH (pH(c)) induced by glutamate in cultured cortical neurons expressing pH-sensitive fluorescent proteins. We found that DCD and MD were associated with a prominent pH(m) decrease which presumably resulted from MPT opening. This pH(m) decrease occurred with some delay after the onset of DCD and MD. This argued against the hypothesis that MPT opening plays a dominant role in triggering of DCD. This conclusion was also supported by experiments in which Ca2+ was replaced with antagonist of MPT opening Sr2+. We found that in Sr2+-containing medium glutamate-induced delayed strontium deregulation (DSD), similar to DCD, which was accompanied by a profound MD. Analysis of the changes in pH(c) and pH(m) associated with DSD led us to conclude that MD in Sr2+-containing medium occurred without involvement of the pore. In contrast, in Ca2+-containing medium such "non-pore mechanism" was responsible only for MD initiation while in the final stages of MD development the MPT played a major role. (C) 2007 Elsevier Ltd. All rights reserved

Influence of neutron irradiation on magnetic field sensors

Parameters of modern experimental set-ups depend on the precision of the magnetic field monitoring under real experimental conditions. As a rule, the conditions of modern experiments (ATLAS, CMS, ALISE, LRC-B) have their special requirements to radiation hardness of the magnetometric apparatus, Specialized magnetic-calibration stands have been manifactured to investigate magnetic field sensors for radiation hardness at the Joint Institute for Nuclear Research (JINR) and at the State University "Lviv Politechnic" (SULP). Characteristics of different magnetic field sensors were studied before and after exposure. The sensors were irradiated at the IBR-2 reactor, JINR, by fast neutrons with the mean energy much less than E much greater than=1.35 MeV up to the fluence of 10(19) n/m(2).</p

Influence of neutron irradiation on magnetic field sensors

Parameters of modern experimental set-ups depend on the precision of the magnetic field monitoring under real experimental conditions. As a rule, the conditions of modern experiments (ATLAS, CMS, ALISE, LRC-B) have their special requirements to radiation hardness of the magnetometric apparatus, Specialized magnetic-calibration stands have been manifactured to investigate magnetic field sensors for radiation hardness at the Joint Institute for Nuclear Research (JINR) and at the State University "Lviv Politechnic" (SULP). Characteristics of different magnetic field sensors were studied before and after exposure. The sensors were irradiated at the IBR-2 reactor, JINR, by fast neutrons with the mean energy much less than E much greater than=1.35 MeV up to the fluence of 10(19) n/m(2)

The Modified Rockwell Test: A New Probe for Mechanical Properties of Metals

In the present work a novel methodology is proposed, based on the combination of the Rockwell and the Vickers tests, to provide estimates of the mechanical properties of metal substrates. The analysis is based on some novel invariants obtained from the finite element solution of the Vickers indentation (the imprint diagonal relates to the maximum indentation depth and the residual indentation depth with the average pressure and the elastic modulus). Several other useful results are discussed and experiments are performed with a modified Rockwell apparatus on steel and aluminium alloys. The results are important for the interpretation of micro indentation tests. Inverting the indentation data, reasonably accurate results can be obtained for strain hardening properties for "power law" behaviour, whereas more complex strain hardening would require further investigation