Front Cell Neurosci
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Front Cell Neurosci · Jan 2016
tACS Phase Locking of Frontal Midline Theta Oscillations Disrupts Working Memory Performance.
Frontal midline theta (FMT) oscillations (4-8 Hz) are strongly related to cognitive and executive control during mental tasks such as memory processing, arithmetic problem solving or sustained attention. While maintenance of temporal order information during a working memory (WM) task was recently linked to FMT phase, a positive correlation between FMT power, WM demand and WM performance was shown. However, the relationship between these measures is not well understood, and it is unknown whether purposeful FMT phase manipulation during a WM task impacts FMT power and WM performance. Here we present evidence that FMT phase manipulation mediated by transcranial alternating current stimulation (tACS) can block WM demand-related FMT power increase (FMTΔpower) and disrupt normal WM performance. ⋯ tACS-related manipulation of FMT phase can disrupt WM performance and influence WM task-related FMTΔpower. This finding may have important implications for the treatment of brain disorders such as depression and attention deficit disorder associated with abnormal regulation of FMT activity or disorders characterized by dysfunctional coupling of brain activity, e.g., epilepsy, Alzheimer's or Parkinson's disease (AD/PD).
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Front Cell Neurosci · Jan 2016
Fractalkine Signaling Attenuates Perivascular Clustering of Microglia and Fibrinogen Leakage during Systemic Inflammation in Mouse Models of Diabetic Retinopathy.
Fractalkine (FKN) is a chemokine expressed constitutively by healthy neurons and signals to microglia upon interaction with the FKN receptor, CX3CR1. Signaling between FKN and CX3CR1 transduces inhibitory signals that ameliorate microglial activation and proinflammatory cytokine release in neuroinflammatory conditions. The aim of this study is to determine the mechanisms associated with microglial activation and vascular leakage during diabetic retinopathy (DR) and under conditions of low-level endotoxemia, common in diabetic patients. ⋯ Lastly, we determined a protective effect of modulating FKN/CX3CR1 signaling in the diabetic retina. We show that intravitreal (iv) administration of recombinant FKN into diabetic FKN-KO mice, reduced fibrinogen deposition and perivascular clustering of microglia in the retina during systemic inflammation. These data suggest that dysregulated microglial activation via loss of FKN/CX3CR1 signaling disrupts the vascular integrity in retina during systemic inflammation.
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Front Cell Neurosci · Jan 2016
Mitochondrial Translocation of High Mobility Group Box 1 Facilitates LIM Kinase 2-Mediated Programmed Necrotic Neuronal Death.
High mobility group box 1 (HMGB1) acts a signaling molecule regulating a wide range of inflammatory responses in extracellular space. HMGB1 also stabilizes nucleosomal structure and facilitates gene transcription. Under pathophysiological conditions, nuclear HMGB1 is immediately transported to the cytoplasm through chromosome region maintenance 1 (CRM1). ⋯ The efficacy of LMB was less effective to attenuate SE-induced neuronal death than that of LIMK2 siRNA. These findings indicate that nuclear HMGB1 release and the subsequent mitochondrial import may facilitate and deteriorate programmed necrotic neuronal deaths. The present data suggest that the nuclear HMGB1 release via CRM1 may be a potential therapeutic target for the programmed necrotic neuronal death induced by SE.
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Front Cell Neurosci · Jan 2016
C1q/Tumor Necrosis Factor-Related Protein-3 Attenuates Brain Injury after Intracerebral Hemorrhage via AMPK-Dependent Pathway in Rat.
C1q/tumor necrosis factor (TNF)-related protein-3 (CTRP3) is a recently discovered adiponectin paralog with established metabolic regulatory properties. However, the role of CTRP3 in intracerebral hemorrhage (ICH) is still mostly unresolved. The aim of the present report was to explore the possible neuroprotective effect of CTRP3 in an ICH rat model and to elucidate the fundamental mechanisms. ⋯ Furthermore, CTRP3 greatly intensified phosphorylation of AMP-activated protein kinase (AMPK) in addition to expression of hypoxia inducing factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF). Finally, the protective effects of CTRP3 could be blocked by either AMPK or VEGF inhibitors. Our findings give the first evidence that CTRP3 is a new proangiogenic and neuroprotective adipokine, which may exert its protective effects at least partly through an AMPK/HIF-1α/ VEGF-dependent pathway, and suggest that CTRP3 may provide a new therapeutic strategy for ICH.