Publications by authors named "José Maurício Siqueira"

4 Publications

  • Page 1 of 1

PI3K, mTOR and GSK3 modulate cytokines' production in peripheral leukocyte in temporal lobe epilepsy.

Neurosci Lett 2021 May 9;756:135948. Epub 2021 May 9.

Neuroscience Program, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil; Department of Pharmacology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. Electronic address:

Introduction: Epilepsy is a common pathological condition that predisposes individuals to seizures, as well as cognitive and emotional dysfunctions. Different studies have demonstrated that inflammation contributes to the pathophysiology of epilepsy. Indeed, seizures change the peripheral inflammatory pattern, which, in turn, could contribute to seizures. However, the cause of the altered production of peripheral inflammatory mediators is not known. The PI3K/mTOR/GSK3β pathway is important for different physiological and pharmacological phenomena. Therefore, in the present study, we tested the hypothesis that the PI3K/mTOR/GSK3β pathway is deregulated in immune cells from patients with epilepsy and contributes to the abnormal production of inflammatory mediators.

Methods: Patients with temporal lobe epilepsy presenting hippocampal sclerosis and controls aged between 18 and 65 years-old were selected for this study. Peripheral blood was collected for the isolation of peripheral mononuclear blood cells (PBMC). Cells were pre-incubated with different PI3K, mTOR and GSK-3 inhibitors for 30 min and further stimulated with phytohaemaglutinin (PHA) or vehicle for 24 h. The supernatant was used to evaluate the production of IL-1β, IL-6, IL-10, TNF e IL-12p70.

Results: Non-selective inhibition of PI3K, as well as inhibition of PI3Kγ and GSK-3, reduced the levels of TNF and IL-10 in PHA-stimulated cells from TLE individuals. This stimulus increased the production of IL-12p70 only in cells from TLE individuals, while the inhibition of PI3K and mTOR enhanced the production of this cytokine. On the other hand, inhibition of GSK3 reduced the PHA-induced production of IL-12p70.

Conclusions: Herein we demonstrated that the production of cytokines by immune cells from patients with TLE differs from non-epileptic patients. This differential regulation may be associated with the altered activity and responsiveness of intracellular molecules, such as PI3K, mTOR and GSK-3, which, in turn, might contribute to the inflammatory state that exists in epilepsy and its pathogenesis.
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http://dx.doi.org/10.1016/j.neulet.2021.135948DOI Listing
May 2021

NLRP3 and NLRP1 inflammasomes are up-regulated in patients with mesial temporal lobe epilepsy and may contribute to overexpression of caspase-1 and IL-β in sclerotic hippocampi.

Brain Res 2021 Feb 29;1752:147230. Epub 2020 Dec 29.

Neuropsychiatry Program, Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, TX, United States.

Inflammation plays a role in the pathophysiology of mesial temporal lobe epilepsy (MTLE). Inflammasome pathways, including the NLRP1 and NLRP3-induced ones, promote neuroinflammation and pyroptosis through interleukin (IL)-1β and caspase-1 action. Evaluation of NLRP1 in sclerotic hippocampi is scarce and there are no data on NLRP3 in human TLE. The aim of this study was to evaluate the expression of these proteins alongside caspase-1 and IL-1β in the hippocampi of patients with TLE compared to control samples. We also sought to investigate peripheral levels of caspase-1 and IL-1β in an independent cohort. Sclerotic and control hippocampi were collected for both histological and immunohistochemical analyses of NLRP1, NLRP3, caspase-1 and IL-1β; plasma was sampled for the measurement of caspase-1 and IL-1β levels through enzyme-linked immunoassay (ELISA) and cytometric bead array (CBA). Sclerotic hippocampi displayed higher expression of the measured proteins than control. Both glia and neurons showed activation of these pathways. Additionally, increased expression of NLRP1 and NLRP3 was associated with elevated plasma levels of IL-1β and in TLE, and increased levels of peripheral caspase-1 were associated with bilateral hippocampal sclerosis (HS). In conclusion, NLRP1 and NLRP3 are up-regulated in sclerotic hippocampi, what may be responsible, at least in part, for the increased hippocampal expression of caspase-1 and IL-1β. Our data suggest a role for inflammasome activation in central and peripheral inflammation in TLE.
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http://dx.doi.org/10.1016/j.brainres.2020.147230DOI Listing
February 2021

Prefrontal cognitive dysfunction following brainstem lesion.

Clin Neurol Neurosurg 2007 May 2;109(4):379-82. Epub 2007 Feb 2.

Department of Neuroscience, Fumec University, Brazil.

Prefrontal cortex (PFC) dysfunction can lead to impairment in planning and behavioral inhibition, as well as personality changes. As ascending monoaminergic brainstem systems modulate PFC functioning, it is possible that lesions in the brainstem lead to symptoms similar to prefrontal dysfunction. A 29-year-old man developed several cognitive and behavioral symptoms after neurosurgery for resection of a pilocytic astrocytoma in the pontine-mesencephalic area. A careful analysis of symptoms indicated PFC dysfunction that could be attributed to lesions in the ascending monoaminergic brainstem systems. Interestingly, the cognitive symptoms improved after treatment with methylphenidate, which is a drug that modules catecholaminergic neurotransmission, thereby supporting this hypothesis. This is a unique case of PFC dysfunction that may be related to post-operative lesion of the catecholaminergic nuclei in the brainstem.
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http://dx.doi.org/10.1016/j.clineuro.2007.01.002DOI Listing
May 2007

Olanzapine for recurrent excessive irritability and psychotic symptoms after mesial temporal lobectomy in a patient with temporal lobe epilepsy.

Epilepsy Behav 2006 Nov 28;9(3):532-4. Epub 2006 Aug 28.

Department of Psychiatry, Raul Soares Institute, Belo Horizonte, Brazil.

We report the case of a patient with temporal lobe epilepsy, nonresponsive to antiepileptic drugs, who became seizure-free, but developed recurrent excessive irritability and psychotic symptoms after successful mesial temporal lobectomy. This patient was refractory to various pharmacological treatments including antipsychotics, mood stabilizers, and benzodiazepines before being successfully treated with olanzapine.
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http://dx.doi.org/10.1016/j.yebeh.2006.07.015DOI Listing
November 2006