Experimental neurology
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Experimental neurology · Sep 2013
Functional consequences of ethidium bromide demyelination of the mouse ventral spinal cord.
Ethidium bromide (EB) has been extensively used in the rat as a model of spinal cord demyelination. However, this lesion has not been addressed in the adult mouse, a model with unlimited genetic potential. Here we characterize behavioral function, inflammation, myelin status and axonal viability following bilateral injection of 0.20 mg/mL ethidium bromide or saline into the ventral white matter (VWM) of female C57Bl/6 mice. ⋯ As these data suggest that EB-injection in the mouse spinal cord is a non-remyelinating lesion, we sought to ask whether wheel running could promote recovery by enhancing plasticity of local lumbar circuitry independent of remyelination. This did not occur as BMS and Treadscan assessment revealed no significant effect of wheel running on recovery. However, this study defines the importance of descending ventral motor pathways to locomotor function in the mouse as VWM loss results in a chronic hindlimb deficit.
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Experimental neurology · Sep 2013
The interaction between the dopaminergic forebrain projections and the medial prefrontal cortex is critical for memory of objects: implications for Parkinson's disease.
Neuropsychological and neuroimaging studies have implicated the dopaminergic nigrostriatal pathway and the prefrontal cortex in learning and memory deficits in patients with Parkinson's disease. However, little is known about how these two brain regions interact in the processing of learning and memory. We employed a disconnection procedure to test whether interaction of these regions contributes to performance in various memory tasks. ⋯ No differences between groups were found in the spatial working memory test. Our data indicate that locomotor, emotional and sensorimotor factors are not likely to confound the results of the memory tests. Thus, the interaction between the dopaminergic forebrain projections, particularly the nigrostriatal dopamine, and the medial prefrontal cortex is critical for object recognition memory but not for spatial working memory in rats.
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Experimental neurology · Sep 2013
Reticulospinal plasticity after cervical spinal cord injury in the rat involves withdrawal of projections below the injury.
Restoring voluntary fine motor control of the arm and hand is one of the main goals following cervical spinal cord injury (SCI). Although the functional improvement achievable with rehabilitative training in rat models is frequently accompanied by corticospinal tract (CST) plasticity, CST rewiring alone seems insufficient to account for the observed recovery. Recent investigations in animal models of SCI have suggested that the reticulospinal tract (RtST) might contribute to mediating improved motor performance of the forelimb. ⋯ However, all analyses directly below the injured spinal level consistently point to a significant decrease of RtST projections. The mechanism and the functional relevance behind this new finding warrant further study. Our results also suggest that mechanisms other than anatomical plasticity, such as plastic changes on a cellular level, might be responsible for the observed spontaneous recovery.
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Experimental neurology · Sep 2013
Endoplasmic reticulum stress contributes to prediabetic peripheral neuropathy.
Growing evidence suggests that prediabetes and metabolic syndrome are associated with increased risk for the development of microvascular complications including retinopathy, nephropathy, and, most commonly, peripheral painful neuropathy and/or autonomic neuropathy. The etiology of these disabling neuropathies is unclear, and several clinical and experimental studies implicated obesity, impaired fasting glycemia/impaired glucose tolerance, elevated triglyceride and non-esterified fatty acids, as well as oxidative-nitrative stress. Endoplasmic reticulum stress resulting from abnormal folding of newly synthesized proteins and leading to the impairment of metabolism, transcriptional regulation, and gene expression, is emerging as a key mechanism of metabolic diseases including obesity and diabetes. ⋯ A chemical chaperone, trimethylamine oxide, blunted endoplasmic reticulum stress and alleviated sensory nerve conduction velocity deficit, thermal and mechanical hypoalgesia, and tactile allodynia. A selective inhibitor of eukaryotic initiation factor-2α dephosphorylation, salubrinal, improved glucose intolerance and alleviated peripheral nerve dysfunction in high-fat diet fed mice. Our findings suggest an important role of endoplasmic reticulum stress in the neurobiology of prediabetic peripheral neuropathy, and identify a new therapeutic target.
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Experimental neurology · Sep 2013
Increased SMA-M1 coherence in Parkinson's disease - Pathophysiology or compensation?
Parkinson's disease (PD) is a common neurodegenerative disorder owing to loss of dopaminergic cells. Akinesia - one of the core symptoms of PD - is associated with exaggerated oscillations at beta frequency (13-30 Hz) within the subthalamic nucleus (STN). Thus, enhanced oscillations below 30 Hz are assumed to represent a pathophysiological marker of PD. ⋯ During rest a significant positive correlation between disease duration and SMA-M1 coherence was found ON but not OFF medication. Conversely, during isometric contraction SMA-M1 coherence and UPDRS III were inversely correlated OFF but not ON medication explaining more than 80% of variance. The results favor the hypothesis that OFF medication exaggerated cortical coherence at beta frequency represents a compensatory mechanism rather than a pathophysiological marker per se.