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Neuroprotective effects of 2,4-dinitrophenol in an acute model of Parkinson’s disease
Lee, Yujeong,Heo, Gwangbeom,Lee, Kyung Moon,Kim, Ah Hyun,Chung, Ki Wung,Im, Eunok,Chung, Hae Young,Lee, Jaewon Elsevier/North Holland 2017 Brain research Vol.1663 No.-
<P><B>Abstract</B></P> <P>Neurons depend on mitochondria for homeostasis and survival, and thus, mitochondrial dysfunction has been implicated in neurodegenerative diseases, including Parkinson’s disease (PD). Increasing evidence indicates the mitochondrial uncoupler, 2,4-dinitrophenol (DNP), protects neurons against neurodegeneration and enhances neural plasticity. Here, the authors evaluated the protective effects of intraperitoneally (i.p.) administered low dose DNP in an acute mouse model of PD. Mice were administered DNP (1 or 5mg/kg) for 12 consecutive days, and then on day 13, MPTP (20mg/kg, i.p.) was administered four times (with 2h intervals between injections) to induce PD. It was found that MPTP-induced motor dysfunction was ameliorated in the DNP-treated mice versus vehicle-treated controls. Additionally, DNP effectively attenuated dopaminergic neuronal loss observed in MPTP treated mice. Moreover, in primary cultured neurons, DNP at 10μM, but not at 100μM, prevented MPP<SUP>+</SUP>-induced cell death and mitochondrial membrane potential (MMP) reduction. In addition, DNP was observed to cause the nuclear translocation of Nrf2 in primary neurons. Taken together, these findings of the present study suggest that DNP protects dopaminergic neurons against neurodegeneration and maintains MMP integrity in PD by activating adaptive stress responses.</P> <P><B>Highlights</B></P> <P> <UL> <LI> DNP attenuates MPTP-induced motor dysfunction and dopaminergic neuronal death. </LI> <LI> DNP pretreatment protects primary neurons against MPP<SUP>+</SUP>-induced cell death. </LI> <LI> Neuroprotective effects of DNP involve stabilization of MMP and adaptive stress response via Nrf2 activation. </LI> </UL> </P>
( Kyoung Won Yoon ),( Hyo Jin Kim ),( Yujeong Im ),( Seul Gi Nam ),( Joo Yeon Lee ),( Hyo Gee Lee ),( Joong-min Park ) 한국정맥경장영양학회 2023 한국정맥경장영양학회지 Vol.15 No.2
Purpose: Parenteral nutrition (PN) is essential for the treatment of patients with malnutrition. The provision of central PN should be recommended by a nutrition support team (NST) made up of a team of experts, even in a newly established hospital. This study sought to evaluate the effectiveness of PN delivered by a multidisciplinary NST in a recently opened hospital. Methods: This was a retrospective study of the effectiveness of a central PN recommendation pop-up message by the electronic medical record (EMR) software to prompt physicians to either calculate the required calorie and protein intake or consult with the NST. The study period was divided into pre-NST and post-NST based on the time of recruitment of NST-dedicated personnel. Results: Patients in the 12-week pre-NST period (n=50) and 12-week post-NST period (n=74) were compared retrospectively. Baseline characteristics were not significantly different between the two groups, except for the median Acute Physiology and Chronic Health Evaluation II score (pre-NST group, 8 [interquartile range, IQR 5-15.5] vs. post-NST group, 15 [IQR 9-24], P=0.012) of the 45 patients total admitted to the intensive care unit. The percentage of patients for whom physicians requested a consultation with the NST for central PN was significantly higher in the post-NST group (52.0% vs. 75.7%, P=0.011). There was no significant difference in achievement of nutrition targets or mortality. Conclusion: Building a multidisciplinary NST may increase awareness of nutritional status and affect the behavior of physicians in recently-opened hospitals.