The renin-angiotensin system is upregulated in the cortex and hippocampus of patients with temporal lobe epilepsy related to mesial temporal sclerosis.
OBJECTIVE
As reported by several authors, angiotensin II (AngII) is a proinflammatory molecule that stimulates the release of inflammatory cytokines and activates nuclear factor kappaB (NFkappaB), being also associated with the increase of cellular oxidative stress. Its production depends on the activity of the angiotensin converting enzyme (ACE) that hydrolyzes the inactive precursor angiotensin I (AngI) into AngII. It has been suggested that AngII underlies the physiopathological mechanisms of several brain disorders such as stroke, bipolar disorder, schizophrenia, and disease. The aim of the present work was to localize and quantify AngII AT1 and AT2 receptors in the cortex and hippocampus of patients with temporal lobe epilepsy related to mesial temporal sclerosis (MTS) submitted to corticoamygdalohippocampectomy for seizure control.


METHODS
Immunohistochemistry, Western blot, and real-time PCR techniques were employed to analyze the expression of these receptors.


RESULTS
The results showed an upregulation of AngII AT1 receptor as well as its messenger ribonucleic acid (mRNA) expression in the cortex and hippocampus of patients with MTS. In addition, an increased immunoexpression of AngII AT2 receptors was found only in the hippocampus of these patients with no changes in its mRNA levels.


CONCLUSIONS
These data show, for the first time, changes in components of renin-angiotensin system (RAS) that could be implicated in the physiopathology of MTS.
Argañaraz
Gustavo Adolfo
GA
Department of Neurology and Neurosurgery, Federal University of Sao Paulo, Sao Paulo, Brazil.
Konno
Ana Carla
AC
Perosa
Sandra Regina
SR
Santiago
Joselita Ferreira Carvalho
JF
Boim
Mirian A
MA
Vidotti
Daniela Berguio
DB
Varella
Pedro Paulo Vasconcelos
PP
Costa
Luciana Gilbert
LG
Canzian
Mauro
M
Porcionatto
Marimélia Aparecida
MA
Yacubian
Elza Márcia
EM
Sakamoto
Américo Ceiki
AC
Carrete
Henrique
H
Centeno
Ricardo Silva
RS
Amado
Débora
D
Cavalheiro
Esper Abrão
EA
Junior
José Antonio Silva
JA
Mazzacoratti
Maria da Graça Naffah
Mda G
D000328:Adult; D000804:Angiotensin II / Q000235:genetics; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics; D012083:Renin; D012084:Renin-Angiotensin System / Q000502:physiology*; D012598:Sclerosis / Q000378:metabolism* / Q000473:pathology*; D013702:Temporal Lobe / Q000378:metabolism* / Q000473:pathology*; D015854:Up-Regulation; D000097782:NF-kappaB-Inducing Kinase
D000804:Angiotensin II; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D012083:Renin; D000097782:NF-kappaB-Inducing Kinase