Evidence for multiple mechanisms responsible for 2,5-hexanedione-induced neuropathy

Lapadula, Daniel M.; Suwita, Elizabeth; Abou‐Donia, Mohamed B.

doi:10.1016/0006-8993(88)90503-3

Cited by 42 publications

(21 citation statements)

References 30 publications

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“…The crosslinking of neurofilaments is assumed to lead to impairment of their transport along the axon, resulting in the accumulation 1,[8][9][10][11][12][13][14] . It is unclear whether such change is a single cause of axonal degeneration, however.…”

Section: Discussionmentioning

confidence: 99%

“…Ten rats were fed for 4 weeks with drinking water containing 2.5% (w/v) of 2,5-HD (HD-exposed rats); this dosing was expected to cause definite neurological changes within a period shorter than those reported using lower concentrations of 2,5-HD in drinking water, i.e. 0.4% for 78 days 29) , 0.5% for 5 weeks 21) , 6 weeks 30) , 2 months 15) and 10-12 weeks 17) , and 1% for 70 days 11) . The remaining rats were fed for the same period without administration of 2,5-HD (control rats).…”

Section: Animalsmentioning

confidence: 93%

“…Although pyrrole-mediated crosslinking of neurofilament proteins by 2,5-HD probably initiates the accumulation of neurofilaments 1,[8][9][10][11][12][13][14] , a bulk of investigations [15][16][17][18][19][20] suggested that a direct effect of 2,5-HD on the nervous tissue is the inhibition of enzymes in glycolysis, leading to studies on glucose utilization rate (GUR, the rate of glucose utilization in the tissue) in experimental 2,5-HD poisoning. Griffiths et al 21) observed reduction in GUR in the superior colliculus of rats exposed to 0.5% 2,5-HD in drinking water for 3 weeks, preceding the morphological changes in the optic pathways to the superior colliculs which were seen after 5 weeks of exposure.…”

Section: Introductionmentioning

confidence: 99%

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Decrease of Glucose Utilization Rate in the Spinal Cord of Experimental 2,5-Hexanedione Poisoning Rats. Application of Microdetermination Technique.

et al. 2000

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To examine the effects of 2,5-hexanedione (HD) on the glucose metabolism in the spinal cord, glucose utilization rate (GUR) and distribution volume of glucose (DV) were measured in the white matter and anterior horn of the spinal cord in 8 rats exposed to HD for 4 weeks and in 10 control rats. The GUR and DV were determined by the quantitative microdetermination method using non-tracer 2-deoxyglucose based on the three-compartments model of Sokoloff. GURs in the white matter and anterior horn and DV in the anterior horn in the HD-exposed rats were significantly lower than those in the control rats. In the multiple regression analysis, GUR in the white matter of HD-exposed rats was significantly related to blood HD concentration. It is suggested that the decrease of GUR in the white matter is a major effect of HD in the spinal cord.

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Section: Discussionmentioning

confidence: 99%

Section: Animalsmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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Decrease of Glucose Utilization Rate in the Spinal Cord of Experimental 2,5-Hexanedione Poisoning Rats. Application of Microdetermination Technique.

et al. 2000

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“…Both these proteins have previously been used to estimate effects on nerve and gtial cells in a variety of neuropathological as well as neul:otoxicological conditions (30)(31)(32)(33)(34)(35)(36). Even so, whereas earlier studies have described the results of 2,5-HD or n-hexane on neuronal and glial intermediate filaments (13,14,16,17), little is known about the consequences of these agents on neuronal and glial marker proteins such as NSE and S-100. In the work of Huang et al (37) increased levels of S-100 protein concentrations were observed in the tail nerve of the rat after long-term n-hexane exposure, while NSE remained and unchanged.…”

Section: Introductionmentioning

confidence: 95%

“…This occurs by the formation of pyrrole adducts with amino groups on amino acid residues (9) enabling cross-linking of NF Institute of Neurobiology, University of Gfteborg, G6teborg, Sweden, 203 proteins (10)(11)(12)(13). The physicochemical properties of the NF are changed (13)(14)(15)(16)(17) interfering with its function and altering axonal transport necessary to maintain normal neuronal function (18)(19)(20). It has also been shown that 2,5-HD inhibits glyceraldehyde-3-phosphate dehydrogenase (21), as well as other glycolytic enzymes, e.g.…”

Section: Introductionmentioning

confidence: 99%

Quantitative alterations of S-100 protein and neuron specific enolase in the rat nervous system after chronic 2,5-hexanedione exposure

et al. 1993

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The regional changes in quantities of the glial S-100 protein and the neuron specific enolase in the rat nervous system have been studied after long-term exposure to 2,5-hexanedione. The wet weights of most of the examined nervous tissues were found to be reduced, with an extensive effect seen in the brain stem. Using dot immunobinding assays, the concentrations of S-100 were found to be increased in most of the examined tissues, but unaffected in the brain stem. The total amount of S-100 per tissue was markedly reduced in the brain stem. The content of neuron specific enolase was reduced only in the brain stem. Thus the effects of 2,5-hexanedione on the nervous system varied regionally. The brain stem was severely atrophied with a reduction of neuronal as well as of glial marker proteins. Other brain regions contained increased glial cell marker proteins as signs of progressive astroglial reactions.

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Triton-soluble phosphovariants of the heavy neurofilament subunit in developing and mature mouse central nervous system

Shea

Dahl²,

Nixon

et al. 1997

J. Neurosci. Res.

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The low abundance of soluble neurofilament (NF) subunits in mature axons has suggested that newly synthesized NF proteins rapidly assemble into highly stable polymers and associate with the Triton X-100-insoluble cytoskeleton. The dynamic nature of these subunit associations in vivo remains unresolved, and the applicability of this assembly model to NFs in other neuronal compartments or to developing neurons is unknown. Here, we report that a unique pool of Triton X-100-soluble, extensively phosphorylated, high molecular weight NF subunits (NF-H, or H-200) are abundantly expressed in the mouse CNS during early postnatal development and persist in the perikaryal compartment of some mature neurons. Triton-soluble H-200 subunits appeared at postnatal day 14 (P14) and remained high through P60, beyond which the percentage declined to marginal levels by P120. Medium and low molecular weight NF (NF-M and NF-L, respectively) were at all times only detectable within the cytoskeleton. Comparison of soluble and cytoskeleton-associated H-200 immunoreactivity indicated that certain phosphorylation-dependent epitopes were confined to the cytoskeleton. Pulse-chase radiolabeling analyses in optic pathway demonstrated that some Triton-soluble NF-H subunits are extensively phosphorylated within retinal perikarya before they are incorporated into Triton-insoluble structures. These findings indicate that the assembly behaviors of NF-H differ substantially from those of NF-M and NF-L, and that the interaction of NF-H with NFs may be more dynamic than is generally recognized, especially during brain development and within specific compartments of mature neurons.

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Evidence for multiple mechanisms responsible for 2,5-hexanedione-induced neuropathy

Cited by 42 publications

References 30 publications

Decrease of Glucose Utilization Rate in the Spinal Cord of Experimental 2,5-Hexanedione Poisoning Rats. Application of Microdetermination Technique.

Decrease of Glucose Utilization Rate in the Spinal Cord of Experimental 2,5-Hexanedione Poisoning Rats. Application of Microdetermination Technique.

Quantitative alterations of S-100 protein and neuron specific enolase in the rat nervous system after chronic 2,5-hexanedione exposure

Triton-soluble phosphovariants of the heavy neurofilament subunit in developing and mature mouse central nervous system

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