Neurotoxin-Induced Neuropeptide Perturbations in Striatum
of Neonatal Rats
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Abstract
The
cyanobacterial toxin β-<i>N</i>-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