Experimental neurology
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Experimental neurology · Nov 2010
The effects of levodopa and ongoing deep brain stimulation on subthalamic beta oscillations in Parkinson's disease.
Local field potentials (LFPs) recorded through electrodes implanted in the subthalamic nucleus (STN) for deep brain stimulation (DBS) in patients with Parkinson's disease (PD) show that oscillations in the beta frequency range (8-20 Hz) decrease after levodopa intake. Whether and how DBS influences the beta oscillations and whether levodopa- and DBS-induced changes interact remains unclear. We examined the combined effect of levodopa and DBS on subthalamic beta LFP oscillations, recorded in nine patients with PD under four experimental conditions: without levodopa with DBS turned off; without levodopa with DBS turned on; with levodopa with DBS turned on; and with levodopa with DBS turned off. ⋯ Another difference was that whereas levodopa completely suppressed beta oscillations, DBS merely decreased them. When we combined levodopa and DBS, the levodopa-induced beta disruption prevailed and combining levodopa and DBS induced no significant additive effect (p=0.500). Our observations suggest that levodopa and DBS both modulate LFP beta oscillations.
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Experimental neurology · Nov 2010
Experience-dependent reactivation of ocular dominance plasticity in the adult visual cortex.
A crucial issue in neurobiology is to understand the main mechanisms restricting neural plasticity to brief windows of early postnatal life. The visual system is one of the paradigmatic models for studying experience-dependent plasticity. The closure of one eye (monocular deprivation, MD) causes a marked ocular dominance (OD) shift of neurons in the primary visual cortex only during the critical period. ⋯ We also found that EE leads to a reduced intracortical GABAergic inhibition and an increased BDNF expression and that the modulation of these molecular factors is neutralized by cortical infusion of the 5-HT synthesis inhibitor pCPA. Our results show that EE rejuvenates the adult visual cortex and that 5-HT is a crucial factor in this process, triggering a cascade of molecular events that allow the reinstatement of neural plasticity. The non-invasive nature of EE makes this paradigm particularly eligible for clinical application.
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Experimental neurology · Nov 2010
Sleep alterations in an environmental neurotoxin-induced model of parkinsonism.
Parkinson's disease (PD) is classically defined as a motor disorder resulting from decreased dopamine production in the basal ganglia circuit. In an attempt to better diagnose and treat PD before the onset of severe motor dysfunction, recent attention has focused on the early, non-motor symptoms, which include but are not limited to sleep disorders such as excessive daytime sleepiness (EDS) and REM behavioral disorder (RBD). However, few animal models have been able to replicate both the motor and non-motor symptoms of PD. ⋯ In addition, cycad-fed rats had significantly fewer orexin cells in the hypothalamus. Our results reveal a novel rodent model of parkinsonism that includes an EDS-like syndrome that may be associated with a dysregulation of orexin neurons. Further characterization of this early, non-motor symptom, may provide potential therapeutic interventions in the treatment of PD.
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Experimental neurology · Nov 2010
Reactive astrocytosis, microgliosis and inflammation in rats with neonatal hydrocephalus.
The deleterious effects of hydrocephalus, a disorder that primarily affects children, include reactive astrocytosis, microgliosis and inflammatory responses; however, the roles that these mechanisms play in the pathophysiology of hydrocephalus are still not clear in terms of cytopathology and gene expression. Therefore we have examined neuroinflammation at both the cellular and the molecular levels in an experimental model of neonatal obstructive hydrocephalus. On post-natal day 1, rats received an intracisternal injection of kaolin to induce hydrocephalus; control animals received saline injections. ⋯ Microarray analysis identified significant (1.5-fold) changes in 1729 of 33,951 genes, including 26 genes out of 185 genes (26/185) in the cytokine-cytokine receptor interaction pathway, antigen processing and presentation pathways (15/66), and the apoptosis pathway (10/69). Collectively, these results demonstrate alterations in normal physiology and an up-regulation of the inflammatory response. These findings lead to a better understanding of neonatal hydrocephalus and begin to form a baseline for future treatments that may reverse these effects.
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Experimental neurology · Oct 2010
Experimental colitis triggers the release of substance P and calcitonin gene-related peptide in the urinary bladder via TRPV1 signaling pathways.
Clinical data provide evidence of high level of co-morbidity among genitourinary and gastrointestinal disorders characterized by chronic pelvic pain. The objective of this study was to test the hypothesis that colonic inflammation can impact the function of the urinary bladder via activation of TRPV1 signaling pathways followed by alterations in gene and protein expression of substance P (SP) and calcitonin gene-related peptide (CGRP) in sensory neurons and in the bladder. Inflammation was induced by intracolonic instillation of trinitrobenzene sulfonic acid (TNBS, 12.5mg/kg), and desensitization of TRPV1 receptors was evoked by intracolonic resiniferatoxin (RTX, 10(-)(7)M). mRNA and protein concentrations of CGRP and SP were measured at 3, 5 and 30 days. ⋯ Protein concentration of CGRP in the spinal cord was diminished by 45-65% (p ≤ 0.05) during colitis. RTX pretreatment did not affect CGRP concentration in the urinary bladder; however, it caused a reduction in CGRP release from lumbosacral DRG neurons during acute phase (3 and 5 days post-TNBS). Our results clearly demonstrate that colonic inflammation triggers the release of pro-inflammatory neuropeptides SP and CGRP in the urinary bladder via activation of TRPV1 signaling mechanisms enunciating the neurogenic nature of pelvic organ cross-sensitization.