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Synaptic plasticity of the hippocampus-prefrontal cortex pathway and its relations with behavioral and molecular changes in rats submitted to febrile seizures during development

Grant number: 12/23918-0
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): May 01, 2013
Effective date (End): June 30, 2016
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:João Pereira Leite
Grantee:Rafael Naime Ruggiero
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated scholarship(s):14/22817-1 - Modulation of prefrontal cortex activity by optogenetic stimulation of ventral tegmental area during fixed interval task: examining how neuronal firing codes timing, BE.EP.DR

Abstract

Febrile seizures are the most common seizure event during childhood and adolescence, although is still a controversial matter if these seizures can lead to subsequent temporal lobe epilepsy (TLE). Experimental studies demonstrate that seizures in the immature brain do not induce classical ELT physiopathology. However, subtle changes in the biochemical machinery and hippocampal synaptic plasticity are found and correlated with impaired memory and learning, behavioral changes and susceptibility to new seizures. Moreover, depression, anxiety, hyperactivity and attention deficits are common findings in children with epilepsy. However, no extra-hippocampal electrophysiological data is available to date in models of early-life seizures. Given the key role of the prefrontal cortex (PFC) in psychiatric symptoms and in cognitive functions such as decision making, attention and working memory, the aim of our study is to characterize the changes generated by two types of febrile seizures (a single prolonged seizure or repeated brief seizures) in synaptic plasticity of hippocampus-PFC and correlate these findings with molecular and behavioral alterations in order to investigate the mechanisms related to these changes. We will assess: (1) changes in synaptic plasticity in the hippocampus-PFC pathway, (2) changes in behavioral memory tasks (object recognition and radial maze) and the taste preference test, (3) neuropathological (neuronal density) and molecular changes (NR1, IL-1², pCREB, CREB, and HLA-DR expression), (4) hippocampal excitability via induction of post-discharge, (5) a possible attenuation of these changes mediating the inflammatory response elicited by the febrile seizures. Our study may contribute to a better understanding of the consequences of seizures during the development and to elucidate further clinically relevant cognitive deficits. (AU)

Scientific publications (5)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
BUENO-JUNIOR, LEZIO S.; PEIXOTO-SANTOS, JOSE E.; RUGGIERO, RAFAEL N.; AVILA, MILTON A. V.; MARQUES, DANILO B.; LOPES-AGUIAR, CLEITON; LEITE, JOAO P. Interaction between hippocampal-prefrontal plasticity and thalamic-prefrontal activity. SCIENTIFIC REPORTS, v. 8, JAN 22 2018. Web of Science Citations: 4.
RUGGIERO, RAFAEL N.; ROSSIGNOLI, MATHEUS T.; DE ROSS, JANA B.; HALLAK, JAIME E. C.; LEITE, JOAO P.; BUENO-JUNIOR, LEZIO S. Cannabinoids and Vanilloids in Schizophrenia: Neurophysiological Evidence and Directions for Basic Research. FRONTIERS IN PHARMACOLOGY, v. 8, JUN 21 2017. Web of Science Citations: 7.
ESTEVES, I. M.; LOPES-AGUIAR, C.; ROSSIGNOLI, M. T.; RUGGIERO, R. N.; BROGGINI, A. C. S.; BUENO-JUNIOR, L. S.; KANDRATAVICIUS, L.; MONTEIRO, M. R.; ROMCY-PEREIRA, R. N.; LEITE, J. P. CHRONIC NICOTINE ATTENUATES BEHAVIORAL AND SYNAPTIC PLASTICITY IMPAIRMENTS IN A STREPTOZOTOCIN MODEL OF ALZHEIMER'S DISEASE. Neuroscience, v. 353, p. 87-97, JUN 14 2017. Web of Science Citations: 5.
ROSSIGNOLI, MATHEUS TEIXEIRA; LOPES-AGUIAR, CLEITON; RUGGIERO, RAFAEL NAIME; DO VAL DA SILVA, RAQUEL ARAUJO; BUENO-JUNIOR, LEZIO SOARES; KANDRATAVICIUS, LUDMYLA; PEIXOTO-SANTOS, JOSE EDUARDO; CRIPPA, JOSE ALEXANDRE; CECILIO HALLAK, JAIME EDUARDO; ZUARDI, ANTONIO WALDO; SZAWKA, RAPHAEL ESCORSIM; ANSELMO-FRANCI, JANETE; LEITE, JOAO PEREIRA; ROMCY-PEREIRA, RODRIGO NEVES. SELECTIVE POST-TRAINING TIME WINDOW FOR MEMORY CONSOLIDATION INTERFERENCE OF CANNABIDIOL INTO THE PREFRONTAL CORTEX: REDUCED DOPAMINERGIC MODULATION AND IMMEDIATE GENE EXPRESSION IN LIMBIC CIRCUITS. Neuroscience, v. 350, p. 85-93, MAY 14 2017. Web of Science Citations: 12.
BUENO-JUNIOR, LEZIO S.; RUGGIERO, RAFAEL N.; ROSSIGNOLI, MATHEUS T.; DEL BEL, ELAINE A.; LEITE, JOAO P.; UCHITEL, OSVALDO D. Acetazolamide potentiates the afferent drive to prefrontal cortex in vivo. PHYSIOLOGICAL REPORTS, v. 5, n. 1 JAN 2017. Web of Science Citations: 1.

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