Neuroscience
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Increasing evidence indicates that Huntington's disease (HD) produces postural control impairments even before the clinical diagnosis. It has been suggested that postural disorders of HD patients are explained by deficits in the processing and integration of sensory information, but this hypothesis has been under-explored. In the present study, we evaluated the amplitude of the center of pressure (COP) displacement during maximum leaning in four directions (forward, backward, rightward and leftward) and under three sensory conditions (eyes open, eyes closed and eyes closed standing on foam). ⋯ Together, these findings demonstrate that HD reduces the limits of stability even before the clinical disease onset. Furthermore, our results indicate that dynamic postural tasks with high demand for sensorimotor integration and especially the use of proprioception are highly sensitive to early HD disease processes. This dynamic postural task may become a useful biomarker of HD progression.
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Epilepsy is a highly common chronic neurological disorder. Although symptomatic treatment is available, 30-40% of epilepsy patients still remain resistant to anti-epileptic drugs. The primary identification and extensive characterization of the pathological substrates underlying epilepsy would facilitate the development of novel treatments, including disease-modifying and anti-epileptogenic therapies. ⋯ Secondly, we review the available approaches for molecular imaging of brain inflammation in general and finally present the current research on the imaging of brain inflammation in patients and experimental models of epilepsy. The current imaging toolbox is limited by the range of neuroinflammatory targets, which can be visualized at present, and in addition, the often indirect approaches used. We believe that research in this field will further advance as highly specific ligands, and producible and practical imaging approaches will become available.
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Toll-like receptor-4 (TLR4) has been identified in primary sensory neurons, both in vivo and in vitro, but is reportedly absent from satellite glial cells (SGCs). Herein we reveal that, in rat dorsal root ganglia (DRG), SGCs do express TLR4 but this expression is inhibited by direct contact with neurons. Thus, TLR4 mRNA and protein is strongly up-regulated in isolated DRG glial cells in the absence of neurons. ⋯ In addition to LPS, conditioned medium from heat-shocked DRG neurons also increased COX-2 mRNA expression in DRG glial cells in a partially TLR4-dependent manner. We therefore hypothesize that neuronal suppression of glial TLR4 activity is a protective mechanism to prevent uncontrolled inflammation within the DRG. Under conditions where DRG neuronal viability is compromised, DRG glial cells become responsive to PAMPs (pathogen-associated molecular patterns) and DAMPs (danger-associated molecular patterns) and generate a range of classical inflammatory responses.
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CCAAT/enhancer binding protein-beta (C/EBP-beta) is a transcription factor that belongs to the C/EBP family. To understand the role of C/EBP-beta in the peripheral nervous system, we investigated the expression of C/EBP-beta in the dorsal root ganglion. C/EBP-beta was weakly detected in nuclei of naive dorsal root ganglion (DRG) neurons. ⋯ Treatment with anti-TNF-alpha prevented SNL-induced pain hypersensitivity and C/EBP-beta expression in the DRG. Injection of TNF-alpha into the sciatic nerve produced transient pain hypersensitivity and induction of C/EBP-beta expression in the DRG. These results demonstrate that C/EBP-beta is activated in the DRG neurons by a TNF-alpha-dependent manner and might be involved in the activation of primary afferent neurons after nerve injury.
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Occurrence of the epileptic seizures during gestation might affect the neurodevelopment of the fetus resulting in cognitive problems for the child later in life. We have previously reported that prenatal pentylenetetrazol (PTZ)-kindling induces learning and memory deficits in the children born to kindled mothers, later in life but the mechanisms involved in this processes are unknown. The cholinergic system plays a major role in learning and memory. ⋯ Our data showed that the retention latencies of pups that received scopolamine (2 or 3μg) were significantly reduced compared to those received normal saline (p<0.05). Interestingly, post training ICV administration of pilocarpine (2μg) retrieved pups' memory deficits (p<0.001). These results demonstrate for the first time, the importance of the central muscarinic cholinergic receptors in learning and memory deficits in pups born to kindled dams and suggest a central mechanism for the cognitive and memory dysfunction, associated with seizures during pregnancy.