3-Nitropropionic acid animal model and Huntington' s disease

Borlongan, Cesario V.; Koutouzis, Theodore K.; Sanberg, Paul R.

doi:10.1016/s0149-7634(96)00027-9

Cited by 167 publications

(73 citation statements)

References 27 publications

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“…The depressive-like behavior or state does not appear to be related to the fatigue or general sickness after 3-NP intoxication, as the duration of immobility for 3-NP treated mice was increased more significantly in modified FST-1, in which mice was forced to swim for only 4 min, 2 min less than the program in routine FST [24,26,29] . According to the literatures, the recognition dysfunction could be seen in animals that systemically received 3-NP, and was dose-dependent [19] .…”

Section: Discussionmentioning

confidence: 95%

“…3-Nitropropionic acid (3-NP), a widely known plant-borne and fungal toxin and an irreversible inhibitor of succinate dehydrogenase of the mitochondrial complex II, induces selective damage to the striatum in humans and animals, and produces HD-like clinical features [19][20][21][22] . Fernagut et al found that subacute systemic administration of 3-NP in mice induced a distinct motor disorder, but most of affected mice strikingly recovered from this motor disorder within 7-10 d [20] .…”

Section: Introductionmentioning

confidence: 99%

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Depressive-like behavior in mice recently recovered from motor disorders after 3-nitropropionic acid intoxication

Zhu

et al. 2008

Neurosci. Bull.

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Objective Striatum may be involved in depressive disorders according to the neuroimaging analysis and clinical data. However, no animal model at present supported the possible role of striatum in the pathogenesis of depression. In the present study, we have investigated the depressive-like behavior in mice recently intoxicated with 3-nitropropionic acid (3-NP), a widely known toxin that selectively damages the striatum in the brain. Methods Mouse model was made with subacute systemic 3-NP treatment, and the depressive-like behavior was measured using the duration of immobility during forced swimming test (FST). Results When the mice at day 15 post-intoxication just totally recovered from motor deficits, the duration of immobility in FST was significantly longer than that in controls. The depressive-like behavior was not due to the fatigue or general sickness following 3-NP intoxication and could be reversed by the antidepressant, desipramine hydrochloride. In two successive FST in 24 h interval, the depressive-like behavior could be observed again in subsequent FST (at day 16 post-intoxication), and the mice presented a normal "learned helplessness". Conclusion A novel depression animal model could be established in mice during the initial period of recovery from 3-NP intoxication. The depression-like behavior might occur independently without involvement of cognitive defects, and the striatal lesions may underlie the depression-like behavior attributable to 3-NP intoxication.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Depressive-like behavior in mice recently recovered from motor disorders after 3-nitropropionic acid intoxication

Zhu

et al. 2008

Neurosci. Bull.

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“…A direct correlation between animal age and neural damage in 3-NP rodent model has been demonstrated in several previous studies [1,24,25] . In rodents less than 6 weeks old, systemic 3-NP injection had no adverse effects, while in older rodents aged over 7 weeks, more severe striatal damage was demonstrated [1] . Lohmann and Riepe found that spatial learning ability was far less affected in the young (4.5 months)…”

Section: Discussionmentioning

confidence: 52%

“…3-Nitropropionic acid (3-NP) is a widely known plantborne and fungal toxin, which could induce neurotoxicity [1][2][3][4] .…”

Section: Introductionmentioning

confidence: 99%

No spatial memory deficit exists in Kunming mice that recently recovered from motor defects following 3-nitropropionic acid intoxication

Zhu

et al. 2009

Neurosci. Bull.

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Objective Numerous studies have described both motor defects and cognitive impairments in several strains of rodents following 3-nitropropionic acid (3-NP) intoxication. In the present study, we investigated spatial recognition memory in Kunming mice that just recovered from motor defects induced by 3-NP. Methods Mouse model was made by systemic subacute 3-NP treatment, and spatial recognition memory was measured through the Y-maze Test, a simple two-trial recognition test. Results (1) On day 15 following 3-NP treatment, affected Kunming mice did not show motor defects in the Rotarod test and presented normal gait again. (2) In the following Y-maze test after 1h interval, the percentage (90.0%) of mice showing novel arm preference in 3-NP treatment group was significantly higher than the random chance level (50%), although it was only slightly higher than that (83.3%) in control group. On day 45 after 3-NP treatment, mice failed to choose unfamiliar novel arm as first choice, and the same occured in the control group. (3) For both post-intoxicated (on day 15 and day 45 following 3-NP treatment) and control groups, the duration in the novel arm and the frequency of entering it, were longer and higher compared with familiar start and other arms. For these mice that recently recovered from motor defects following 3-NP intoxication, no spatial memory deficits were observed through Y-maze Test. Conclusion Kunming mice used in our assays might possess resistance to cognitive impairment induced by 3-NP, which is consistent with previous findings in Swiss EPM-M1 mice.

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“…Thus, embryonic striatal primortoms in motor, cognitive, and psychiatric domains (34). dium will survive in the degenerative striatum of rats In early experimental animal models of the disease, exand monkeys following excitotoxic, metabolic, or ischecitotoxic or metabolic challenge of striatal neurons can mic lesions, where the implanted cells are seen to differsimilarly induce striatal neuronal degeneration and asentiate and express a wide range of markers appropriate sociated deficits in motor and cognitive domains in to a normal striatal phenotype (19), to extend neurites mice, rats, cats, and primates (8,16,61). Since the idenand establish reciprocal connections with the host brain tification of the genetic mutation in HD involving an (73), to exhibit electrophysical and neurochemical indiexpanded trinucleotide repeat in a novel gene on chroces of functional activity (13,69,75), and to alleviate mosome 4 (37), encoding an expanded polyglutamine both motor and cognitive deficits that result from the repeat in a protein, huntingtin, of unknown function, a initial lesions (23,39,54).…”

Section: Introductionmentioning

confidence: 99%

Transplanted hNT Cells (“LBS Neurons”) in a Rat Model of Huntington's Disease: Good Survival, Incomplete Differentiation, and Limited Functional Recovery

2004

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A variety of immortalized cell lines have been proposed to exhibit sufficient phenotypic plasticity to allow them to replace primary embryonic neurons for restorative cell transplantation. In the present experiments we evaluate the functional viability of one particular cell line, the hNT cells developed by Layton Bioscience, to replace lost neurons and alleviate asymmetrical motor deficits in a unilateral excitotoxic lesion model of Huntington's disease. Because the grafts involved implantation of human-derived cells into a rat host environment, all animals were immunosuppressed. Cyclosporin A and FK-506 were similar in providing effective immunoprotection of the hNT xenografts, and whereas the lesions induced a marked inflammatory response in the host brain, this was not exacerbated by the presence of xenograft cells. The presence of grafted cells was determined with the human-specific antigen HuNu, and good graft survival was demonstrated in almost all animals up to the longest survival examined, 16 weeks posttransplantation. Although the cells exhibited progressively greater maturation and differentiation at 10-day, 4-and 16-week time points, staining for the mature neuronal marker NeuN was at best very weak, and we were unable to detect unequivocal staining with any markers of mature striatal phenotype, including DARPP-32, calbindin, parvalbumin, choline acetyl transferase, or NADPH diaphorase (with in all cases positive control provided by good staining on the intact contralateral side of the brain). Nor were we able to detect any differences between rats with lesions alone and rats with grafts in the contralateral motor deficits exhibited in a test of skilled paw reaching or cylinder placing. These results suggest that further and more extensive studies should be undertaken to assess whether hNT neurons can show more extensive and appropriate maturation and be associated with recovery in appropriate behavioral models, before they may be considered a suitable replacement for primary embryonic cells for clinical application in Huntington's disease.

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3-Nitropropionic acid animal model and Huntington' s disease

Cited by 167 publications

References 27 publications

Depressive-like behavior in mice recently recovered from motor disorders after 3-nitropropionic acid intoxication

Depressive-like behavior in mice recently recovered from motor disorders after 3-nitropropionic acid intoxication

No spatial memory deficit exists in Kunming mice that recently recovered from motor defects following 3-nitropropionic acid intoxication

Transplanted hNT Cells (“LBS Neurons”) in a Rat Model of Huntington's Disease: Good Survival, Incomplete Differentiation, and Limited Functional Recovery

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