RESUMO
A body of evidence supports a relevant role of brain-derived neurotrophic factor (BDNF) in temporal lobe epilepsy (TLE). Magnetic resonance data reveal that the cerebral atrophy extends to regions that are functionally and anatomically connected with the hippocampus, especially the temporal cortex. We previously reported an increased expression of BDNF messenger for the exon VI in the hippocampus of temporal lobe epilepsy patients compared to an autopsy control group. Altered levels of this particular transcript were also associated with pre-surgical use of certain psychotropic. We extended here our analysis of transcripts I, II, IV, and VI to the temporal cortex since this cerebral region holds intrinsic communication with the hippocampus and is structurally affected in patients with TLE. We also assayed the cyclic adenosine monophosphate response element-binding (CREB) and glucocorticoid receptor (GR) genes as there is experimental evidence of changes in their expression associated with BDNF and epilepsy. TLE and pre-surgical pharmacological treatment were considered as the primary clinical independent variables. Transcripts BDNF I and BDNF VI increased in the temporal cortex of patients with pharmacoresistant TLE. The expression of CREB and GR expression follow the same direction. Pre-surgical use of selective serotonin reuptake inhibitors, carbamazepine (CBZ) and valproate (VPA), was associated with the differential expression of specific BDNF transcripts and CREB and GR genes. These changes could have functional implication in the plasticity mechanisms related to temporal lobe epilepsy.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Córtex Cerebral/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Epilepsia do Lobo Temporal/metabolismo , Receptores de Glucocorticoides/metabolismo , Adolescente , Idoso , Fator Neurotrófico Derivado do Encéfalo/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Epilepsia do Lobo Temporal/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de Glucocorticoides/genética , Adulto JovemRESUMO
A putative role of the brain-derived neurotrophic factor (BDNF) in epilepsy has emerged from in vitro and animal models, but few studies have analyzed human samples. We assessed the BDNF expression of transcripts with exons I (BDNFI), II (BDNFII), IV (BDNFIV) and VI (BDNFVI) and methylation levels of promoters 4 and 6 in the hippocampi of patients with pharmaco-resistant temporal lobe epilepsy (TLE) (n=24). Hippocampal sclerosis (HS) and pre-surgical pharmacological treatment were considered as clinical independent variables. A statistical significant increase for the BDNFVI (p<0.05) was observed in TLE patients compared to the autopsy control group (n=8). BDNFVI was also increased in anxiety/depression TLE (N=4) when compared to autopsies or to the remaining group of patients (p<0.05). In contrast, the use of the antiepileptic drug Topiramate (TPM) (N=3) was associated to a decrease in BDNFVI expression (p<0.05) when compared to the remaining group of patients. Methylation levels at the BDNF promoters 4 and 6 were similar between TLE and autopsies and in relation to the use of either Sertraline (SRT) or TPM. These results suggest an up-regulated expression of a specific BDNF transcript in patients with TLE, an effect that seems to be dependent on the use of specific drugs.