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Objective To investigate the mechanism of nootkatone (NKT) in mitigating depression-like behavior caused by blast traumatic brain injury (TBI). Methods The rat bTBI depression-like model was established by simulating the shock wave parameters of blast overpressure (BOP of 60 kPa, 90 kPa, and 120 kPa) with a biological shock wave tube. After 14 days of exposure, we evaluated the depression-like behavior of rats using the tail suspension test and forced swimming test. We identified that the BOP (120 kPa) condition caused the most noticeable depressive behavior and used this condition for subsequent experiments. Thirty male SD rats were randomly divided into sham operation group, bTBI group (BOP of 120 kPa), and bTBI+NKT group [at 1 d after exposure to BOP of 120 kPa, giving NKT 10 mg/(kg·d) orally for 14 days], 10 in each group. After 14 days of exposure, the depression-like behavior of rats was evaluated by tail suspension test and forced swimming test. The expression levels of protein kinase A (PKA), phosphorylated cyclic adenosine monophosphate effector binding protein (pCREB), and brain-derived neurotrophic factor (BDNF) in the hippocampus of rat were determined by Western blotting. Immunohistochemistry was used to detect the generation of proliferating cell nuclear antigen (PCNA)-labeled neurons in the hippocampal dentate gyrus (DG). Results BOP of 90 kPa can cause depression-like in rats and BOP of 120 kPa can cause the most noticeable depressive behavior (P<0.05). Therefore, we selected the BOP exposure of 120 kPa for subsequent experiments. After 14 days of BOP exposure, compared with sham operation group, the immobility time of tad suspension test in bTBI group was prolonged (P<0.05), the latency of for ced swimming test was shortened, the immobility time was prolonged (P<0.05), the expression levels of PKA, pCREB and BDNF protein in hippocampus were lowered (P<0.05), and the number of PCNA-labeled neurons in hippocampal DG area was reduced (P<0.05); compared with the bTBI group, the immobility time of tail suspension test in bTBI+NKT group was shortened (P<0.05), the latency of forced swimming test was prolonged, the immobility time was shortened (P<0.05), the expression levels of PKA, pCREB and BDNF protein in hippocampus were increased (P<0.05), and the number of PCNA-labeled neurons in hippocampal DG area was increased (P<0.05). Conclusions Early treatment with NKT can improve depression-like behavior in mild bTBI rats. The mechanism may be related to the up-regulation of the PKA-CREB-BDNF signaling pathway and increased expression levels of pCREB and BDNF in the hippocampus, which results in increased neuron numbers in the DG region of the hippocampus.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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