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Background: Bradykinesia, tremor, rigidity and postural instability are the hallmark of Parkinson's disease (PD). Non-motor symptoms including cognitive, behavioral, and neuropsychiatric changes, sensory and sleep disturbances that may precede the motor symptoms by years. The peculiar pathological features of PD are decreased dopaminergic neurons and dopamine levels in the substantia nigra pars compacta and pontine locus coeruleus. Humanin is produced by a small gene peptide, which is located in the mitochondria genome. Inflammation, oxidative stress, mitochondrial dysfunction and altered transcription have been recognized as causative factors of PD. This evidence has prompted many researchers to focus on studying the functions of DNA and mitochondria. The purpose of the present study was to evaluate Humanin mRNA levels in peripheral blood mononuclear cells (PBMCs) of PD subjects, compared with those in PBMCs of normal control (NC) subjects. Methods and results: A total of 220 participants, including 154 PD patients (57 females and 97 males; mean age 71.54 years, SD 7.8) and 66 CN (28 females and 38 males; mean age 70.54 years, SD 9.45) were enrolled for the qRT-PCR analysis. Increased Humanin mRNA levels were found in PD samples, compared to controls. Conclusion: In conclusion, the present data confirm the tendency of mitochondria to overexpress mRNA in PD, which could be a cellular attempt to reduce apoptotic damage in PD subjects. Humanin might be useful as a marker for a better diagnosis of PD, and we cannot exclude that in the future it might also play a role on prognosis and in the possible therapies for PD. [ABSTRACT FROM AUTHOR]

It has recently been accepted that long-term high-fat diet (HFD) intake is a significant possible cause for prediabetes and cognitive and brain dysfunction through the disruption of brain mitochondrial function and dynamic balance. Although modulation of mitochondrial dynamics by inhibiting fission and promoting fusion has been shown to reduce the morbidity and mortality associated with a variety of chronic diseases, the impact of either pharmacological inhibition of mitochondrial fission (Mdivi-1) or stimulation of fusion (M1) on brain function in HFD-induced prediabetic models has never been studied. Thirty-two male Wistar rats were separated into 2 groups and fed either a normal diet (ND, n = 8) or HFD (n = 24) for 14 weeks. At week 12, HFD-fed rats were divided into 3 subgroups (n = 8/subgroup) and given an intraperitoneal injection of either saline, Mdivi-1 (1.2 mg/kg/day), or M1 (2 mg/kg/day) for 2 weeks. Cognitive function and metabolic parameters were determined toward the end of the protocol. The rats then were euthanized, and the brain was immediately removed in order to evaluate brain mitochondrial function and mitochondrial dynamics. HFD-fed rats experienced prediabetes, evidenced by elevated plasma insulin and the HOMA index, impaired mitochondrial function in the brain, altered dynamic regulation, and cognitive impairment were also found. Mdivi-1 and M1 treatment exerted neuroprotection to a similar extent by improving metabolic parameters, balancing mitochondrial dynamics, and reducing mitochondrial dysfunction, resulting in a gradual increase in cognitive function. Therefore, pharmacological targeting of mitochondrial fission and fusion protected the brain against chronic HFD-induced prediabetes. [ABSTRACT FROM AUTHOR]

Purpose: Garlic has been shown to exhibit antioxidant effects and cardioprotective properties. However, the effects of garlic extract on the heart in insulin resistance induced by long-term high-fat-diet consumption are not well defined. Therefore, we sought to determine the effects of garlic extract in the obese insulin-resistant rats. Methods: Male Wistar rats (180-200 g) were divided into two groups: normal-diet or high-fat-diet ( n = 24/group) fed for 12 weeks. Rats in each groups were divided into three subgroups ( n = 8 each): vehicle or garlic extract (250 or 500 mg/kg/day, respectively) treated for 28 days. At the end of the treatment, the metabolic parameters, heart rate variability (HRV), cardiac function, and cardiac mitochondrial function were determined. Results: Rats that received a high-fat-diet for 12 weeks had increased body weight, visceral fat, plasma insulin levels, total cholesterol, oxidative stress levels, depressed HRV, and cardiac mitochondrial dysfunction. Garlic extract at both concentrations significantly decreased the plasma insulin, total cholesterol, homeostasis model assessment index, and oxidative stress levels. Furthermore, garlic extract at both doses restored the HRV, cardiac function, and cardiac mitochondrial function. Conclusion: We concluded that garlic extract at both concentrations exerted cardioprotective effects against cardiac dysfunction and mitochondrial dysfunction in obese insulin-resistant rats. [ABSTRACT FROM AUTHOR]