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Roszkowska, M.

Publications and source records attributed to Roszkowska, M..

3 recordsLinked to original sources

Serum response factor is essential for synaptic maturation in the hippocampus

Disturbances of gene expression patterns that occur during brain development can severely affect signal transmission, connectivity, and plasticity--key features that underlie memory formation and storage in neurons. Abnormalities at the molecular level can manifest as changes in the structural and functional plasticity of dendritic spines that harbor excitatory synapses. This can lead to such developmental neuropsychiatric conditions as Autism spectrum disorders, intellectual disabilities, and schizophrenia. The present study investigated the role of the major transcriptional regulator serum response factor (SRF) in synapse maturation and its impact on behavioral phenotypes. Using in vitro and in vivo models of early postnatal SRF deletion, we studied its influence on key morphological and physiological hallmarks of spine development. The elimination of SRF in developing neurons resulted in a phenotype of immature dendritic spines and impairments in excitatory transmission. Moreover, using a combination of molecular and imaging techniques, we showed that SRF-depleted neurons exhibited a lower level of specific glutamate receptor mRNAs and a decrease in their surface expression. Additionally, the early postnatal elimination of SRF in hippocampal CA1 excitatory neurons caused spine immaturity and a specific social deficit that is frequently observed in autism patients. Altogether, our data suggest that the regulation of structural and functional dendritic spine maturation begins at the stage of gene transcription, which underpins the crucial role of such transcription factors as SRF. Moreover, disturbances of the postnatal expression of SRF translate to behavioral changes in adult animals.

neuroscience

The tardigrade Hypsibius exemplaris as an emerging model to study the mitochondrial alternative oxidase at animal organismal level

Mitochondrial alternative oxidase (AOX) is present in mitochondria of many invertebrates. Independently of the reason concerning the enzyme occurrence in animal mitochondria, expression of AOX in human mitochondria is regarded as a potential therapeutic strategy. Till now, relevant data were obtained due to heterologous AOX expression in cells and animals without natively expressed AOX. Application of animals natively expressing AOX importantly contribute the research. Thus, we investigated Hypsibius exemplaris as a model for AOX activity analysis. We observed that H. exemplaris tolerance to the blockage of the MRC complexes was diminished in the presence of AOX inhibitor and the inhibitor-sensitive respiration enabled the tardigrade respiration under condition of the blockage. Furthermore, although detection of AOX at protein level and pronounced oxygraphic registration of its activity required the MRC complex blockage, the obtained data indicated that AOX clearly contributed animal functioning. We demonstrated that AOX activity in tardigrades, can be monitored by measurement of intact specimen whole-body respiration. Furthermore, it was also possible to monitor the impact of the MRC complex IV blockage on AOX expression and AOX inhibition in the absence of the blockage on animal functioning. Thus, H. exemplaris is applied as a whole-animal model suitable to study AOX.

molecular biology

Mitochondrial alternative oxidase contributes to successful tardigrade anhydrobiosis

Anhydrobiosis can be described as an adaptation to lack of water. This adaptation provides some organisms including tardigrades with a set of capabilities allowing them to survive extreme conditions that even do not exist on Earth. However, the underlying cellular mechanisms are still not explained. Available data assumes important contribution of mitochondrial proteins. Since mitochondrial alternative oxidase (AOX) described as a drought response element has recently been proposed for various invertebrates including tardigrades, we have decided to check if AOX is involved in successful anhydrobiosis of tardigrades. Milnesium inceptum was used as a model for the study. We confirmed functionality of M. inceptum AOX and estimated its activity contribution to anhydrobiosis of different duration. We observed that AOX activity was particularly important for M. inceptum revival after longer-term anhydrobiosis but did not affect rehydration stage. The results may contribute to explanation and then application of anhydrobiosis underlying mechanisms.

cell biology