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Neurotoxin-Induced Neuropeptide Perturbations in Striatum of Neonatal Rats
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology. (Drug Safety and Toxicology)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
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2013 (English)In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 12, no 4, 1678-1690 p.Article in journal (Refereed) Published
Abstract [en]

The cyanobacterial toxin β-N-methylamino-l-alanine (BMAA) is suggested to play a role in neurodegenerative disease. We have previously shown that although the selective uptake of BMAA in the rodent neonatal striatum does not cause neuronal cell death, exposure during the neonatal development leads to cognitive impairments in adult rats. The aim of the present study was to characterize the changes in the striatal neuropeptide systems of male and female rat pups treated neonatally (postnatal days 9-10) with BMAA (40-460 mg/kg). The label-free quantification of the relative levels of endogenous neuropeptides using mass spectrometry revealed that 25 peptides from 13 neuropeptide precursors were significantly changed in the rat neonatal striatum. The exposure to noncytotoxic doses of BMAA induced a dose-dependent increase of neurosecretory protein VGF-derived peptides, and changes in the relative levels of cholecystokinin, chromogranin, secretogranin, MCH, somatostatin and cortistatin-derived peptides were observed at the highest dose. In addition, the results revealed a sex-dependent increase in the relative level of peptides derived from the proenkephalin-A and protachykinin-1 precursors, including substance P and neurokinin A, in female pups. Because several of these peptides play a critical role in the development and survival of neurons, the observed neuropeptide changes might be possible mediators of BMAA-induced behavioral changes. Moreover, some neuropeptide changes suggest potential sex-related differences in susceptibility toward this neurotoxin. The present study also suggests that neuropeptide profiling might provide a sensitive characterization of the BMAA-induced noncytotoxic effects on the developing brain.

Place, publisher, year, edition, pages
2013. Vol. 12, no 4, 1678-1690 p.
Keyword [en]
neurotoxin, BMAA, neonatal striatum, neuropeptide, ALS/PDC, cyanobacteria, sex differences, cortistatin
National Category
Pharmacology and Toxicology
Research subject
Toxicology; Developmental Neurosciences
Identifiers
URN: urn:nbn:se:uu:diva-196966DOI: 10.1021/pr3010265ISI: 000317327500013PubMedID: 23410195OAI: oai:DiVA.org:uu-196966DiVA: diva2:611278
Note

De två första författarna delar förstaförfattarskapet.

Available from: 2013-03-15 Created: 2013-03-15 Last updated: 2017-12-06Bibliographically approved

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Karlsson, OskarKultima, KimWadensten, HenrikNilsson, AnnaRoman, ErikaAndrén, Per E.Brittebo, Eva B.

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Karlsson, OskarKultima, KimWadensten, HenrikNilsson, AnnaRoman, ErikaAndrén, Per E.Brittebo, Eva B.
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