title: Neurotoxin-induced neuropeptide perturbations in striatum of neonatal rats.
abstract: 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.
authors: Department of Pharmaceutical Biosciences, Uppsala University , SE-751 24 Uppsala, Sweden.
authors: Oskar
authors: O
authors: Karlsson
authors: Kim
authors: K
authors: Kultima
authors: Henrik
authors: H
authors: Wadensten
authors: Anna
authors: A
authors: Nilsson
authors: Erika
authors: E
authors: Roman
authors: Per E
authors: PE
authors: Andrén
authors: Eva B
authors: EB
authors: Brittebo
mesh_terms: D000595:Amino Acid Sequence; D000599:Amino Acids, Diamino / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D002766:Cholecystokinin / Q000378:metabolism; D002864:Chromogranins / Q000378:metabolism; D000087522:Cyanobacteria Toxins; D004305:Dose-Response Relationship, Drug; D004745:Enkephalins / Q000378:metabolism; D005260:Female; D008297:Male; D008969:Molecular Sequence Data; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism*; D009479:Neuropeptides / Q000032:analysis / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012737:Sex Factors
chemical_list: D000599:Amino Acids, Diamino; D002864:Chromogranins; D000087522:Cyanobacteria Toxins; D004745:Enkephalins; D009479:Neuropeptides; D011498:Protein Precursors; C099323:cortistatin; C029992:proenkephalin; C001824:beta-N-methylamino-L-alanine; C060249:procholecystokinin; D002766:Cholecystokinin; C033660:preproenkephalin