Distribution and Long-term Effects of the Environmental Neurotoxin β-N-methylamino-L-alanine (BMAA): Brain changes and behavioral impairments following developmental exposure

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Distribution and Long-term Effects of the Environmental Neurotoxin β-N-methylamino-L-alanine (BMAA) : Brain changes and behavioral impairments following developmental exposure

Karlsson, Oskar, 1980- (författare): Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Toxikologi

Brittebo, Eva, Professor (preses): Uppsala universitet,Institutionen för farmaceutisk biovetenskap

Lindquist, Nils Gunnar, Professor (preses): Uppsala universitet,Institutionen för farmaceutisk biovetenskap

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Roman, Erika, Docent (preses): Uppsala universitet,Institutionen för farmaceutisk biovetenskap

Ceccatelli, Sandra, Professor (opponent): Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden

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ISBN 9789155479848
Uppsala : Acta Universitatis Upsaliensis, 2010
Engelska 79 s.
Serie: Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, 1651-6192 ; 134

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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)

Abstract Ämnesord

Stäng

Many cyanobacteria are reported to produce the nonprotein amino acid β-N-methylamino-L-alanine (BMAA). Cyanobacteria are extensively distributed in terrestrial and aquatic environments and recently BMAA was detected in temperate aquatic ecosystems, e.g. the Baltic Sea. Little is known about developmental effects of the mixed glutamate receptor agonist BMAA. Brain development requires an optimal level of glutamate receptor activity as the glutamatergic system modulates many vital neurodevelopmental processes. The aim of this thesis was to investigate the developmental neurotoxicity of BMAA, and its interaction with the pigment melanin. Autoradiography was utilized to determine the tissue distribution of 3H-labelled BMAA in experimental animals. Behavioral studies and histological techniques were used to study short and long-term changes in the brain following neonatal exposure to BMAA. Long-term changes in protein expression in the brain was also investigated using matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS). A notable targeting of 3H-BMAA to discrete brain regions e.g. hippocampus and striatum in mouse fetuses and neonates was determined by autoradiography. BMAA treatment of neonatal rats on postnatal days 9–10 induced acute but transient ataxia and hyperactivity. Postnatal exposure to BMAA also gave rise to reduced spatial learning and memory abilities in adulthood. Neonatal rat pups treated with BMAA at 600 mg/kg showed early neuronal cell death in the hippocampus, retrosplenial and cingulate cortices. In adulthood the CA1 region of the hippocampus displayed neuronal loss and astrogliosis. Lower doses of BMAA (50 and 200 mg/kg) caused impairments in learning and memory function without any acute or long-term morphological changes in the brain. The MALDI IMS studies, however, revealed changes in protein expression in the hippocampus and striatum suggesting more subtle effects on neurodevelopmental processes. The studies also showed that BMAA was bound and incorporated in melanin and neuromelanin, suggesting that pigmented tissues such as in the substantia nigra and eye may be sequestering BMAA. In conclusion, the findings in this thesis show that BMAA is a developmental neurotoxin in rodents. The risks posed by BMAA as a potential human neurotoxin merits further consideration, particularly if the proposed biomagnifications in the food chain are confirmed.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)

Nyckelord

ALS/PDC
Guam
Developmental neurotoxicity
Brain growth spurt
Behavior
Nonprotein amino acid
Excitotoxic
Cyanobacteria
Apoptosis
BMAA
environmental toxin
Algal blooming
Algblomning
algtoxin
alggift
hjärnutveckling
Toxicology
Toxikologi
Toxicology
Toxikologi

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