Tags

Type your tag names separated by a space and hit enter

Neuropathological and behavioral changes induced by various treatment paradigms with MPTP and 3-nitropropionic acid in mice: towards a model of striatonigral degeneration (multiple system atrophy).
Acta Neuropathol. 2003 Aug; 106(2):157-66.AN

Abstract

We characterized two models of dual nigral and striatal lesions replicating the lesion pattern of striatonigral degeneration, the neuropathological hallmark of parkinsonism associated with multiple system atrophy (SND/MSA-P). For this purpose, we used systemic administration of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) and 3-nitropropionic acid (3-NP) in C57BL mice. One group of animals was first injected with MPTP followed by 3NP (MPTP+3-NP model). In the second group 3-NP was injected first, followed by MPTP (3-NP+MPTP model). The behavioral and neuropathological characteristics of these two models were compared to those observed after single 3-NP or MPTP intoxication. Results showed that, compared to control mice, spontaneous nocturnal locomotor activity was preserved in the MPTP+3-NP model, whereas it was reduced by 27% (P<0.05) in the 3-NP+MPTP model and in animals treated with either 3-NP (27%, P<0.05) or MPTP (23%, P<0.05) alone. Quantitative histological evaluation based on Nissl staining and DARPP-32 immunohistochemistry revealed that 3-NP alone and 3-NP+MPTP treatment produced a marked (greater than 50%) loss of striatal neurons, whereas MPTP+3-NP treatment attenuated loss of striatal neurons by 43%. Further, loss of tyrosine hydroxylase-positive neurons in substantia nigra pars compacta (SNc) was attenuated after 3-NP+MPTP treatment compared to that observed after MPTP (40% vs 74%, P<0.001) and MPTP+3NP treatment (55% vs 74%, P<0.01). Our results show that MPTP-induced nigral lesions attenuate 3-NP toxicity and, reciprocally, that 3-NP-induced striatal lesions reduce MPTP toxicity. This suggests that complex integrative mechanisms are likely to regulate the vulnerability of the striatum and SNc to cell death in SND/MSA-P.

Authors+Show Affiliations

Department of Neurology, University Hospital of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12764627

Citation

Stefanova, Nadia, et al. "Neuropathological and Behavioral Changes Induced By Various Treatment Paradigms With MPTP and 3-nitropropionic Acid in Mice: Towards a Model of Striatonigral Degeneration (multiple System Atrophy)." Acta Neuropathologica, vol. 106, no. 2, 2003, pp. 157-66.
Stefanova N, Puschban Z, Fernagut PO, et al. Neuropathological and behavioral changes induced by various treatment paradigms with MPTP and 3-nitropropionic acid in mice: towards a model of striatonigral degeneration (multiple system atrophy). Acta Neuropathol. 2003;106(2):157-66.
Stefanova, N., Puschban, Z., Fernagut, P. O., Brouillet, E., Tison, F., Reindl, M., Jellinger, K. A., Poewe, W., & Wenning, G. K. (2003). Neuropathological and behavioral changes induced by various treatment paradigms with MPTP and 3-nitropropionic acid in mice: towards a model of striatonigral degeneration (multiple system atrophy). Acta Neuropathologica, 106(2), 157-66.
Stefanova N, et al. Neuropathological and Behavioral Changes Induced By Various Treatment Paradigms With MPTP and 3-nitropropionic Acid in Mice: Towards a Model of Striatonigral Degeneration (multiple System Atrophy). Acta Neuropathol. 2003;106(2):157-66. PubMed PMID: 12764627.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuropathological and behavioral changes induced by various treatment paradigms with MPTP and 3-nitropropionic acid in mice: towards a model of striatonigral degeneration (multiple system atrophy). AU - Stefanova,Nadia, AU - Puschban,Zoe, AU - Fernagut,Pierre-Olivier, AU - Brouillet,Emmanuel, AU - Tison,François, AU - Reindl,Markus, AU - Jellinger,Kurt A, AU - Poewe,Werner, AU - Wenning,Gregor K, Y1 - 2003/05/23/ PY - 2003/02/18/received PY - 2003/04/11/revised PY - 2003/04/11/accepted PY - 2003/5/24/pubmed PY - 2003/10/2/medline PY - 2003/5/24/entrez SP - 157 EP - 66 JF - Acta neuropathologica JO - Acta Neuropathol VL - 106 IS - 2 N2 - We characterized two models of dual nigral and striatal lesions replicating the lesion pattern of striatonigral degeneration, the neuropathological hallmark of parkinsonism associated with multiple system atrophy (SND/MSA-P). For this purpose, we used systemic administration of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) and 3-nitropropionic acid (3-NP) in C57BL mice. One group of animals was first injected with MPTP followed by 3NP (MPTP+3-NP model). In the second group 3-NP was injected first, followed by MPTP (3-NP+MPTP model). The behavioral and neuropathological characteristics of these two models were compared to those observed after single 3-NP or MPTP intoxication. Results showed that, compared to control mice, spontaneous nocturnal locomotor activity was preserved in the MPTP+3-NP model, whereas it was reduced by 27% (P<0.05) in the 3-NP+MPTP model and in animals treated with either 3-NP (27%, P<0.05) or MPTP (23%, P<0.05) alone. Quantitative histological evaluation based on Nissl staining and DARPP-32 immunohistochemistry revealed that 3-NP alone and 3-NP+MPTP treatment produced a marked (greater than 50%) loss of striatal neurons, whereas MPTP+3-NP treatment attenuated loss of striatal neurons by 43%. Further, loss of tyrosine hydroxylase-positive neurons in substantia nigra pars compacta (SNc) was attenuated after 3-NP+MPTP treatment compared to that observed after MPTP (40% vs 74%, P<0.001) and MPTP+3NP treatment (55% vs 74%, P<0.01). Our results show that MPTP-induced nigral lesions attenuate 3-NP toxicity and, reciprocally, that 3-NP-induced striatal lesions reduce MPTP toxicity. This suggests that complex integrative mechanisms are likely to regulate the vulnerability of the striatum and SNc to cell death in SND/MSA-P. SN - 0001-6322 UR - https://www.unboundmedicine.com/medline/citation/12764627/Neuropathological_and_behavioral_changes_induced_by_various_treatment_paradigms_with_MPTP_and_3_nitropropionic_acid_in_mice:_towards_a_model_of_striatonigral_degeneration__multiple_system_atrophy__ L2 - https://dx.doi.org/10.1007/s00401-003-0717-y DB - PRIME DP - Unbound Medicine ER -