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Hippocampal pathological plasticity in neonatal anoxia

Grant number: 22/09277-4
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): December 01, 2022
Effective date (End): November 30, 2024
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Alexander Henning Ulrich
Grantee:Guilherme Shigueto Vilar Higa
Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:18/07366-4 - Purine and kinin receptors as targets of study and therapeutic interventions in neurological diseases, AP.TEM


Postnatal development events determine the establishment of neuronal networks and cognition. Neuronal network formation is based on synaptogenesis and synaptic refinement that occur intensely during the so-called critical period of development. Due to its properties, the period of establishment of the neuronal circuitry is highly susceptible to the occurrence of persistent changes in cognitive development. Oxygen deprivation during birth, known as anoxia or neonatal hypoxia, is a highly prevailing insult occurring during the critical period. Neonatal anoxia can trigger cognitive and motor disturbances, which makes neonatal anoxia an important public health burden worldwide. Therefore, the objective of this project is to evaluate the effects of neonatal anoxia on hippocampal synaptic plasticity, assessing in vitro and in vivo models that mimic the anoxia conditions that occur in human preterm infants. Our thesis is that anoxia promotes long-term synaptic potentiation (LTP) saturation by increasing the excitation-inhibition ratio, and by the increased release of ATP and adenosine. From this perspective, the global and dysfunctional increase in excitatory connections strength, caused by anoxia, would deplete LTP, preventing the availability and use of this form of plasticity during the critical period and thus limiting the correct postnatal neuronal development normally guided by experience-dependent plasticity. Thus, this project aims to promote a broad understanding of the impact of neonatal anoxia and the possible mechanisms by which this insult triggers cognitive problems in adult individuals, helping to identify possible therapeutic targets.

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