| Summary: | 碩士 === 國立陽明大學 === 生物醫學工程學系 === 107 === Cognitive function impairment was shown that associated with metabolic syndrome (MetS). Nucleus accumbens (NAc) was responsible for dopamine sensing and glucose metabolism which deep brain stimulation (DBS) at NAc could improve mitochondrial function in prefrontal cortex, whereas NAc-DBS for memory-related cognitive function was yet to be investigated. This study explored whether NAc-DBS changed mitochondria function of dopaminergic pathway in two species of mice, including C57BL/6 mice as wild-type (WT) mice and CCL5/RANTES knock out (k.o.) mice as MetS model. In WT mice, the ratio of oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) significantly increased in medial prefrontal cortex (mPFC) (p = 0.004) and ventral hippocampus (vHIPP) (p = 0.007), but decreased in NAc (p = 0.008) after NAc-DBS; phosphorylated 5' adenosine monophosphate-activated protein kinase (pAMPK) significantly decreased in mPFC (p = 0.006), NAc (p = 0.002) and VTA (p = 0.004); peroxisome proliferator activated receptor gamma coactivator 1 alpha (PGC-1α) significantly increased in mPFC (p = 0.006) and vHIPP (p = 0.020) with cognitive function improvement by novel object recognition test (NOR) (p = 0.009). In CCL5/RANTES k.o. mice, the OCR and ECAR significantly increased in mPFC (p = 0.012) and VTA (p = 0.007), but decreased in NAc (p = 0.016); the pAMPK significantly decreased in mPFC (p = 0.032), vHIPP (p = 0.027) and VTA (p = 0.002) but significantly increased in NAc (p = 0.032); the PGC-1α significantly increased in NAc (p = 0.042) and vHIPP (p = 0.008); the presynaptic protein, synaptophysin significantly increased in mPFC (p = 0.038), NAc (p = 0.021) and vHIPP (p = 0.041). In addition, cognitive function significantly improved in NOR (p = 0.042) and restored functional connectivity (FC) of dopaminergic pathway after NAc-DBS was reported (p < 0.05). Taken together, NAc-DBS improved cognitive function in both C57BL/6 and CCL5/RANTES mice, associating with improved metabolic function and mitochondrial biogenesis of dopaminergic pathway.
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