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Contenuto archiviato il 2022-12-23

Effect of severe hypoxia and hypoxic preconditioning on expression of metalloproteases and their role in learning and memory

Obiettivo

The project is designed to investigate the role of specific enzymes, namely metalloproteases, especially belonging to the ADAMs (a disintegrin and metalloprotease) family, in the development of the brain, learning and memory under normal conditions and after severe hypoxia, which is one of the most common complications accompanying impaired brain metabolism caused by various internal and environmental factors. The hypothesis is that there may be various types of correlation between the levels of expression of different metalloproteases of the ADAMs and NEP families in the brain structures participating in the control of motor behaviour, learning and memory (sensorimotor cortex, striatum, amygdala and, hippocampus) of the brain at different stages of postnatal development that will be significantly influenced by hypoxia with and without preconditioning. To this end the analysis of expression of several metalloproteases (ADAMs 9, 10, 15 and 17) and DINE (damage induced neuronal endopeptidase) in brain structures regulating learning and memory at different stages of development under normal conditions and after severe hypoxia with and without preconditioning will be performed.

This complex study of the problem at molecular, morphological and behavioural levels will reveal a correlation between the expression of different metalloproteases in various brain structures with the level of motor behaviour and learning abilities of animals before and after severe hypoxia. The specific characteristics of ADAM expression in vulnerable (CA1/CA2 of hippocampus, striatum, neocortex) and tolerant (dentate gyrus, thalamus) regions will also be explored. Administration of specific inhibitors of metalloproteases into the structures controlling motor behaviour and formation of new reflexes with analysis of short-term memory of rats will testify exactly which metalloproteases might be involved in the process of learning and memory. These data will be further interpreted from the point of view of their possible implication for the development of a therapeutic strategy for the treatment of impaired brain functions caused by ischemic insults and neurodegenerative diseases.

Invito a presentare proposte

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Meccanismo di finanziamento

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Coordinatore

University of Leeds
Contributo UE
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Indirizzo
Mount Preston Street
LS2 9JT Leeds
Regno Unito

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Partecipanti (3)