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Outline
To explore the effect of rotenone exposure on the metabolic homeostasis of nicotinamide adenine dinucleotide (NAD+) in dopaminergic neurons of the rat mid-brain striatum, and investigate the effect of exogenous NAD+ intervention on the cellular damage response of dopaminergic neurons induced by rotenone.
Male SD rats (8 weeks old, 200~250 g) were divided into a control group using a table of random numbers, a rotenone exposure group, an NAD+-intervention group, and an NAD+ group. An intoxication model was established in the rotenone exposure group. NAD+ (250 mg/kg) was administered simultaneously with rotenone exposure in the NAD+ -intervention group. The NAD+ group was only given NAD+, while the control group received no intervention. After modeling, open field test was performed to evaluate behavioral changes. After scarification, serum samples and mid-brain striatal tissues were collected. HE staining was used to observe the morphology of dopaminergic neurons in the striatum. The NAD+ content in the tissues was detected with NAD+/NADH kit. Western blotting was employed to determine the contents of tyrosine hydroxylase (TH), nicotinamide phosphoribosyltransferase (NAMPT), nicotinamide mononucleotide adenylyltransferase (NMNAT), and solute carrier family 25 member A51 (SLC25A51). ELISA was utilized to measure the content of dopamine in the striatal tissues. Immunohistochemical staining was applied to observe the distribution and contents of TH proteins in the striatal tissues of each group.
Rotenone exposure significantly affected the vital signs and motor abilities of rats, induced disorderly-arranged, atrophy and deformed neurons in the striatal tissue, decreased the content of TH, rate-limiting enzyme for dopamine synthesis, by approximately 29% (P<0.01), the content of dopamine by about 42%, and that of NAD+ by almost 50% (P<0.01), while increased the NADH/NAD+ ratio (P<0.01). After exposure, the content of NAMPT, an enzyme related to NAD+ synthesis, was decreased by 26% (P<0.05), the contents of NMNAT1-3 and SLC25A51, mitochondrial transporters of NAD+ by approximately 21%, 38%, 43%, and 21%, respectively (P<0.01). Exogenous NAD+ intervention improved the motor function of exposure rats and the morphology of dopaminergic neurons in the mid-brain striatal tissue, and restored the content of TH in the striatal tissue significantly by 12.8% (P<0.05), and the content of dopamine by 20.9% (P<0.05).
Rotenone disrupts the NAD+ homeostasis in dopaminergic neurons by inhibiting the NAD+ synthesis and transport pathways in the mid-brain striatal tissues, while exogenous NAD+ intervention can effectively alleviate the dopaminergic neuron damage induced by rotenone exposure.
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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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