Neurobiology of disease
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Neurobiology of disease · Feb 2001
The gene for slow Wallerian degeneration (Wld(s)) is also protective against vincristine neuropathy.
Neurological diseases are frequently associated with axonal degeneration, which leads to dysfunction though separation of neurons from their targets. The mechanisms of axonal degeneration are largely unknown and in many cases are independent of those occurring within cell bodies in neurodegenerative disorders. The Wld(s) mouse mutant demonstrates the unique phenotype of resistance to axonal degeneration after axotomy (slow Wallerian degeneration), making it a powerful tool for studying mechanisms of axonal degeneration. ⋯ Using cultured dorsal root ganglion neurons we compared the course of axonal degeneration in response to exposure to the neurotoxin vincristine and found that Wld(s) neurites were relatively resistant to vincristine neuropathy. These findings suggest common pathophysiologic mechanisms between axotomy-induced Wallerian degeneration and toxic neuropathy. The implications are wide-ranging and are relevant to the pathophysiology of axonal degeneration seen in a wide spectrum of neurological diseases ranging from stroke and head trauma to spinal cord injury and peripheral neuropathy.
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Neurobiology of disease · Dec 2000
Brain-derived neurotrophic factor in astrocytes, oligodendrocytes, and microglia/macrophages after spinal cord injury.
Recent studies suggest that the injured adult spinal cord responds to brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3) with enhanced neuron survival and axon regeneration. Potential neurotrophin sources and cellular localization in spinal cord are largely undefined. We examined glial BDNF localization in normal cord and its temporospatial distribution after injury in vivo. ⋯ Ten millimeters from the lesion, astrocyte and microglia/macrophage BDNF-immunolabeling resembled that at the injury at all times examined. Twenty millimeters from injury, BDNF localization in all three glial subtypes resembled controls, regardless of time postlesion. Our findings suggest that in normal adult cord, astrocytes, oligodendrocytes, and microglia/macrophages play roles in local trophin availability and in trophin-mediated injury and healing responses directly within and surrounding the wound site.
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Neurobiology of disease · Oct 1999
The T102C polymorphism of the 5-HT2A-receptor gene in fibromyalgia.
Based on a possible involvement of serotonergic dysfunction in the pathophysiology of fibromyalgia (FM) and on preliminary reports of a possible genetically driven vulnerability for this disorder we investigated the silent T102C polymorphism of the 5-HT2A-receptor gene in 168 FM patients and 115 healthy controls. Our results showed a significantly different genotype distribution in FM patients with a decrease in T/T and an increase in both T/C and C/C genotypes as compared to the control population (Fisher's Exact test, two-sided, P = 0.008). However, the increase in allele-C102 frequency felt short of significance (P = 0.07). ⋯ In contrast to that the pain score, being a self reported information on pain severity, was significantly higher in patients of the T/T genotype (Mann-Whitney U test, P = 0.028). This suggests that the T102-allele might be involved in the complex circuits of nociception. However, the T102C polymorphism is not directly involved in the aetiology of FM but might be in linkage dysequilibrium with the true functional variant, which has to be unravelled.
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Neurobiology of disease · Jun 1999
Involvement of oxidative stress on the impairment of energy metabolism induced by A beta peptides on PC12 cells: protection by antioxidants.
Alzheimer's disease is widely held to be associated with oxidative stress due, in part, to the membrane action of amyloid beta-peptide (A beta) aggregates. In this study, the involvement of oxidative stress on A beta-induced energy metabolism dysfunction was evaluated on PC12 cells. ⋯ Taken together, these data suggest that exposure of PC12 cells to A beta results in an impairment of energy metabolism, leading to a deficit in ATP levels and to the compromise of cellular viability. Furthermore, the generation of ROS seems to be a crucial event responsible for the energetic metabolic dysfunction induced by A beta.
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The use of cannabis for the management of a wide range of painful disorders has been well documented in case reports throughout history. However, clinical evaluations of cannabis and its psychoactive constituent THC have not led to a consensus regarding their analgesic effectiveness. ⋯ The endogenous ligand, anandamide, is also an effective antinociceptive agent. The extent to which the endogenous cannabinoid system is involved in the modulation of pain is currently unknown.