Neonatal Dexamethasone Treatment Increased Depression-like Behavior in Adult Rats
| Autor: | Ko Meng Chang, 柯孟昌 |
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| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 103 Synthetic glucocorticoid dexamethasone (DEX) is frequently used as a therapeutic agent to lessen the morbidity of chronic lung disease in premature infants. Previous studies suggested that neonatal DEX treatment altered brain development and cognitive function. It has been recognized that the amygdala is involved in emotional processes and also a critical site of neuronal plasticity for fear conditioning. Little is known about the possible long-term adverse effect of neonatal DEX treatment on amygdala function. The present study was aimed to evaluate the possible effect of neonatal DEX treatment on the synaptic function of amygdala in adult rats. Newborn Wistar rats were subjected to subcutaneous injection of tapering dose of DEX (0.5 mg/kg, 0.3 mg/kg and 0.1 mg/kg) from postnatal day 1 to 3, PN1~PN3. The animals were then studied by forced swim test (FST) and electrophysiological recording at the age of 8 weeks. Results showed neonatal DEX treatment increased depression-like behavior in adulthood which had been determined by FST. After acute stress evoking, the percentage of time spent in free floating was significantly increased in the DEX treated group as compared with the control animals. Furthermore, neonatal DEX treatment elevated long-term potentiation (LTP) response and the phosphorylation level of MAPK in lateral nucleus of amygdala (LA). Compared with control group, corticosterone (CORT) in plasma was significantly increased in DEX treated group after acute stress pre-exposed FST without influencing amygdaloid total amount of glucocorticoid receptor (GR). Intracerebroventricular infusion of MAPK inhibitor, PD98059 exhibited certain reverse effects, including the reduction of depression-like behavior and the restoration of LTP to normal range, implying that the behavior disorder could be reduced through a modification of the ionic conduction of the neuron cell. Pre-treatment of the potent inhibitor of histone deacetylase (HDAC) trichostatin A (TSA) prevented the adverse effects caused by neonatal DEX treatment. This finding implied that the defective effects of neonatal DEX treatment might be mediated by the epigenetic regulatory processes. In conclusion, our results suggested that neonatal DEX treatment may disrupt amygdala development and gene expression which then let to an resulted in adverse consequence in the adult age, such as the enhancement of the susceptibility for depression disorder in later life. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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