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Although it has been recognized that energy metabolism and mitochondrial structure and functional activity in the immature brain differs from that of the adult, few studies have examined mitochondria specifically at the neuronal synapse during postnatal brain development. In this study, we examined the presynaptic mitochondrial proteome in mice at postnatal day 7 and 42, a period that involves the formation and maturation of synapses. Application of two independent quantitative proteomics approaches - SWATH-MS and super-SILAC - revealed a total of 40 proteins as significantly differentially expressed in the presynaptic mitochondria. In addition to elevated levels of proteins known to be involved in ATP metabolic processes, our results identified increased levels of mitoNEET (Cisd1), an iron-sulfur containing protein that regulates mitochondrial bioenergetics. We found that mitoNEET overexpression plays a cell-type specific role in ATP synthesis and in neuronal cells promotes ATP generation. The elevated ATP levels in SH-SY5Y neuroblastoma cells were associated with increased mitochondrial membrane potential and a fragmented mitochondrial network, further supporting a role for mitoNEET as a key regulator of mitochondrial function.

HIV-related neurocognitive impairment (NCI) may increase the risk of death. However, a survival disadvantage for patients with NCI has not been well studied in the post-combination antiretroviral therapy (cART) era. Specifically, limited research has been conducted considering the reversible nature and variable progression of the impairment and this area demands further evaluation. We performed multivariable Cox proportional hazards modeling to assess the association between baseline NCI (global T scores) and mortality. A joint modeling approach was then used to model the trajectory of global neurocognitive functioning over time and the association between neurocognitive trajectory and mortality. Among the National NeuroAIDS Tissue Consortium’s (NNTC) HIV-infected participants, we found a strong negative association between NCI and mortality in the older age groups (e.g., at age = 55, HR = 0.79; 95% CI 0.64–0.99). Three neurocognitive sub-domains (abstraction and executive functioning, speed of information processing, and motor) had the strongest negative association with mortality. Joint modelling indicated a 33% lower hazard for every 10-unit increase in global T scores (HR = 0.67; 95% CI 0.56–0.80). The study identified older HIV-infected individuals with NCI as a group needing special attention for the longevity of life. The study has considerable prognostic utility by not only predicting mortality hazard, but also future cognitive status.

Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta. Gait abnormalities, including decreased arm swing, slower walking speed, and shorter steps are common in PD patients and appear early in the course of disease. Thus, the quantification of motor patterns in animal models of PD will be important for phenotypic characterization during disease course and upon therapeutic treatment. Most cases of PD are idiopathic; however, the identification of hereditary forms of PD uncovered gene mutations and variants, such as loss-of-function mutations in Pink1 and Parkin, two proteins involved in mitochondrial quality control that could be harnessed to create animal models. While mice are resistant to neurodegeneration upon loss of Pink1 and Parkin (single and combined deletion), in rats, Pink1 but not Parkin deficiency leads to nigral DA neuron loss and motor impairment. Here, we report the utility of FTIR imaging to uncover gait changes in freely walking young (2 months of age) male rats with combined loss of Pink1 and Parkin prior to the development of gross visually apparent motor abnormality as these rats age (observed at 4-6 months), characterized by hindlimb dragging as previously reported in Pink1 knockout (KO) rats.

Herein we present major updates to the National NeuroAIDS Tissue Consortium (NNTC) database. The NNTC's ongoing multisite clinical research study was established to facilitate access to ante-mortem and post-mortem data, tissues and biofluids for the neurohuman immunodeficiency virus (HIV) research community. Recently, the NNTC has expanded to include data from the central nervous system HIV Antiretroviral Therapy Effects Research (CHARTER) study. The data and biospecimens from CHARTER and NNTC cohorts are available to qualified researchers upon request. Data generated by requestors using NNTC biospecimens and tissues are returned to the NNTC upon the conclusion of requestors' work, and this external, experimental data are annotated and curated in the publically accessible NNTC database, thereby extending the utility of each case. A flexible and extensible database ontology allows the integration of disparate data sets, including external experimental data, clinical neuropsychological and neuromedical testing data, tissue pathology and neuroimaging data.