Assuntos
Transtorno Depressivo/diagnóstico , Pacientes Internados/psicologia , Questionário de Saúde do Paciente/normas , Escalas de Graduação Psiquiátrica/normas , Psicometria/normas , Adolescente , Adulto , Idoso , Argentina/epidemiologia , Comorbidade , Estudos Transversais , Transtorno Depressivo/epidemiologia , Feminino , Hospitalização , Hospitais Gerais , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria/instrumentação , Adulto JovemRESUMO
Sustained motor improvement in human patients with idiopathic Parkinson's disease has been described following electroconvulsive shock (ECS) treatment. In rats, ECS stimulates the expression of various trophic factors (TFs), some of which have been proposed to exert neuroprotective actions. We previously reported that ECS protects the integrity of the rat nigrostriatal dopaminergic system against 6-hydroxydopamine (6-OHDA)-induced toxicity; in order to shed light into its neuroprotective mechanism, we studied glial cell-line derived neurotrophic factor (GDNF) levels (the most efficient TF for dopaminergic neurons) in the substantia nigra (SN) and striatum of 6-OHDA-injected animals with or without ECS treatment. 6-OHDA injection decreased GDNF levels in the SN control animals, but not in those receiving chronic ECS, suggesting that changes in GDNF expression may participate in the ECS neuroprotective mechanism. To evaluate this possibility, we inhibit GDNF by infusion of GDNF function blocking antibodies in the SN of 6-OHDA-injected animals treated with ECS (or sham ECS). Animals were sacrificed 7 days after 6-OHDA infusion, and the integrity of the nigrostriatal system was studied by tyrosine hydroxylase immunohistochemistry and Cresyl Violet staining. Neuroprotection observed in ECS-treated animals was inhibited by GDNF antibodies in the SN. These results robustly demonstrate that GDNF is essential for the ECS neuroprotective effect observed in 6-OHDA-injected animals.
Assuntos
Eletrochoque , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Transtornos Parkinsonianos/metabolismo , Transtornos Parkinsonianos/terapia , Animais , Sobrevivência Celular , Eletroconvulsoterapia , Imuno-Histoquímica , Masculino , Neurônios/metabolismo , Ratos , Ratos WistarRESUMO
In neuronal cultures it has been demonstrated that neurotrophins can elicit neuronal death through the p75 neurotrophic receptor (p75ntr) in the absence of concomitant Trk signaling. However, it was suggested that p75ntr induces neuronal death after status epilepticus (SE) in neuronal populations that express relatively high quantities of tropomyosin receptor kinase B (TrkB). Here, using Western blot and immunohistochemistry analyses in the hippocampus, we found that 3-h SE caused a remarkable decrease in TrkB expression and phosphorylation, and a significant increase in p75ntr. TrkB modification occurs before the overexpression of the tumor suppressor protein p53, accompanies the cell damage taking place in the dentate gyrus, and precedes the CA1 neuronal injury as assessed by Fluoro-Jade B and Nissl staining. Co-immunoprecipitation of brain-derived neurotrophic factor (BDNF) or its immature form proBDNF showed increased interaction with p75ntr after its binding to TrkB was reduced. Interestingly, proBDNF also increases its binding with p75ntr after seizures that do not cause neuronal death (animals injected with pilocarpine that fail to enter SE). However, in those animals, TrkB protein levels remained unchanged and its phosphorylation increased. Our results indicate an intrinsic capacity of neurons in vivo to modify final neurotrophin output by changing the proportion of their receptors' expression and the receptors' interaction with their ligands. These early events support the idea that neurotrophins may be involved in the induction of neuronal death in vivo under pathological conditions.