A critical review of the postulated role of the non-essential amino acid, ß-N-methylamino-L-alanine, in neurodegenerative disease in humans.

The compound BMAA (ß-N-methylamino-L-alanine) has been postulated to play a significant role in four serious neurological human diseases: Amyotrophic Lateral Sclerosis/Parkinsonism Dementia Complex (ALS/PDC) found on Guam, and ALS, Parkinsonism, and dementia that occur globally. ALS/PDC with symptoms of all three diseases first came to the attention of the scientific community during and after World War II. It was initially associated with cycad flour used for food because BMAA is a product of symbiotic cycad root-dwelling cyanobacteria. Human consumption of flying foxes that fed on cycad seeds was later suggested as a source of BMAA on Guam and a cause of ALS/PDC. Subsequently, the hypothesis was expanded to include a causative role for BMAA in other neurodegenerative diseases including Alzheimer's disease (AD) through exposures attributed to proximity to freshwaters and/or consumption of seafood due to its purported production by most species of cyanobacteria. The hypothesis that BMAA is the critical factor in the genesis of these neurodegenerative diseases received considerable attention in the medical, scientific, and public arenas. This review examines the history of ALS/PDC and the BMAA-human disease hypotheses; similarities and differences between ALS/PDC and the other diseases with similar symptomologies; the relationship of ALS/PDC to other similar diseases, studies of BMAA-mediated effects in lab animals, inconsistencies and data gaps in the hypothesis; and other compounds and agents that were suggested as the cause of ALS/PDC on Guam. The review concludes that the hypothesis of a causal BMAA neurodegenerative disease relationship is not supported by existing data.

Effects of alcohol exposure during development on social behavior in rats.

In addition to the cognitive deficits associated with fetal alcohol syndrome (FAS), clinical and animal studies indicate that alcohol exposure might also have detrimental effects on social behavior. In a rat model of FAS, experimental rats were given alcohol from gestational day (GD) 1 to 22 and from postnatal day (PD) 2 to 10, a period roughly equivalent to all three trimesters in humans. Control groups consisted of rats exposed to the administration procedures but not to alcohol and nontreated rats. At 30 days of age, rats were tested for social behavior in an alley maze that contained its cagemate in the goal box. After varying periods of isolation, the animals' latencies to reach the goal box and their social behaviors once inside the goal box were recorded. Alcohol-exposed animals ran faster than control rats to the occupied goal box regardless of the amount of isolation. The alcohol-exposed animals also exhibited aberrant social interactions with their cagemate once inside the goal box compared to one or both of the control groups. Specifically, the alcohol-exposed animals showed greater amounts of anogenital sniffing, chasing, hopping and darting, and retrieving and lesser amounts of pinning and biting compared to one or both of the control groups. The alcohol-induced change in anogenital sniffing varied over increasing amounts of isolation compared to both control groups, but the alterations in the other behaviors did not. It is argued that the altered social behavior of alcohol-exposed animals is not the result of changes in the animals' motivational state or social learning and may be the result of an increased responsiveness to social stimuli.