RESUMO
Electroacupuncture (EA) is a clinically useful physiological therapy that has been recently adopted to treat several brain disorders. However, the potential role of early EA intervention in the prevention of posttraumatic stress disorder (PTSD) as well as its potential cellular and molecular mechanism has never been investigated previously. In the present study, we used an enhanced single prolonged stress (ESPS) model to access the effects of early EA intervention on the prevention of anxiety-like and fear learning behaviors, as well as the influence of the expression of post-synaptic density protein 95 (PSD95), synaptophysin (Syn), brain derived neurotrophic factor (BDNF), diacylglycerol lipase alpha (DAGLα) and cannabinoid type 1 receptor (CB1R) in the hippocampus with or without DAGLα or CB1R knockdown by a short hairpin RNA (shRNA) in the hippocampus. Moreover, the effects of electrical stimulation with different parameters on the expression of DAGLα and CB1R in the hippocampal astrocytes were also observed. The results showed that Early EA intervention improved hippocampal synaptic plasticity and ameliorated PTSD-like behaviors and also increased expression of BDNF, DAGLα and CB1R. However, either DAGLα or CB1R knockdown by a short hairpin RNA (shRNA) eliminated the neuroprotective effects of early EA intervention. Furthermore, electrical stimulation with 2/15â¯Hz 1â¯mA elevated the expression of DAGLα and CB1R. Altogether, our findings provide new insights regarding the possibility of using early EA intervention in the prevention of PTSD, and the protective effects of EA is involving the activation of DAGLα and CB1R.
Assuntos
Eletroacupuntura , Endocanabinoides/metabolismo , Hipocampo/metabolismo , Transtornos de Estresse Pós-Traumáticos/prevenção & controle , Animais , Western Blotting , Modelos Animais de Doenças , Eletroacupuntura/métodos , Masculino , Aprendizagem em Labirinto , Plasticidade Neuronal , Testes Neuropsicológicos , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais , Transtornos de Estresse Pós-Traumáticos/terapiaRESUMO
To determine the role of toll-like receptors (TLRs) myeloid differentiation factor 88 (MyD88) dependent pathway in the spinal cord secondary injury, compression injury was made at T8 segment of the spinal cord in adult male Sprague-Dawley rats. Shown by RT-PCR, TLR4 mRNA in the spinal cord was quickly elevated after compression injury. Intramedullary injection of MyD88 inhibitory peptide (MIP) resulted in significant improvement in locomotor function recovery at various time points after surgery. Meanwhile, injury area, p38 phosphorylation, and proinflammation cytokines in the injured spinal cord were significantly reduced in MIP-treated animals, compared with control peptide (CP) group. These data suggest that TLRs MyD88-dependent pathway may play an important role in the development of secondary spinal cord injury, and inhibition of this pathway at early time after primary injury could effectively protect cells from inflammation and apoptosis and therefore improve the functional recovery.