Neurobiology of disease
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Neurobiology of disease · Mar 2014
Cortistatin attenuates inflammatory pain via spinal and peripheral actions.
Clinical pain, as a consequence of inflammation or injury of peripheral organs (inflammatory pain) or nerve injury (neuropathic pain), represents a serious public health issue. Treatment of pain-related suffering requires knowledge of how pain signals are initially interpreted and subsequently transmitted and perpetuated. To limit duration and intensity of pain, inhibitory signals participate in pain perception. ⋯ The analgesic effects of cortistatin were independent of its anti-inflammatory activity and directly exerted on peripheral and central nociceptive terminals via Gαi-coupled somatostatin-receptors (mainly sstr2) and blocking intracellular signaling that drives neuronal plasticity including protein kinase A-, calcium- and Akt/ERK-mediated release of nociceptive peptides. Moreover, cortistatin could modulate, through its binding to ghrelin-receptor (GHSR1), pain-induced sensitization of secondary neurons in spinal cord. Therefore, cortistatin emerges as an anti-inflammatory factor with potent analgesic effects that offers a new approach to clinical pain therapy, especially in inflammatory states.
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Neurobiology of disease · Mar 2014
D1 receptor agonist improves sleep-wake parameters in experimental parkinsonism.
Both excessive daytime sleepiness (EDS) and rapid eye movement (REM) sleep deregulation are part of Parkinson's disease (PD) non-motor symptoms and may complicate dopamine replacement therapy. We report here that dopamine agonists act differentially on sleep architecture in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine macaque monkey. Continuous sleep and wake electroencephalographic monitoring revealed no effect of the selective dopamine D2 receptor agonist quinpirole on EDS, whereas the selective dopamine D1 receptor agonist SKF38393 efficiently alleviated EDS and restored REM sleep to baseline values. The present results question the relevance of abandoning D1 receptor agonist treatment in PD as it might actually improve sleep-related disorders.
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Neurobiology of disease · Mar 2014
MiR-139-5p inhibits HGTD-P and regulates neuronal apoptosis induced by hypoxia-ischemia in neonatal rats.
Human growth transformation dependent protein (HGTD-P) is a newly identified protein that promotes neuronal apoptosis in hypoxia-ischemia brain damage (HIBD) in neonatal rats. However, the mechanisms regulating HGTD-P expression are not clear. Here we describe microRNAs targeted to HGTD-P and examine their effects on regulating neuronal apoptosis in HIBD. ⋯ In conclusion, HI induces inhibitors which block the processing step of pre-miR-139, resulting in the down-regulation of mature miR-139-5p. The down-regulation of miR-139-5p plays a critical role in the up-regulation of HGTD-P expression. MiR-139-5p agomir attenuates brain damage when used 12h after HI, providing a longer therapeutic window than anti-apoptosis compounds currently available.
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Neurobiology of disease · Mar 2014
Longitudinal assessment of blood-brain barrier leakage during epileptogenesis in rats. A quantitative MRI study.
The blood-brain barrier (BBB) plays an important role in the homeostasis of the brain. BBB dysfunction has been implicated in the pathophysiology of various neurological disorders, including epilepsy in which it may contribute to disease progression. Precise understanding of BBB dynamics during epileptogenesis may be of importance for the assessment of future therapies, including BBB leakage blocking-agents. ⋯ Furthermore, our MRI data revealed non-uniform BBB leakage throughout epileptogenesis. This study demonstrates BBB leakage in specific brain regions during epileptogenesis, which can be quantified using MRI. Therefore, MRI may be a valuable tool for experimental or clinical studies to elucidate the role of the BBB in epileptogenesis.