Long-term Cognitive Impairments in Adult Rats Treated Neonatally with β-N-Methylamino-L-Alanine

Abstract

Most cyanobacteria (blue-green algae) can produce the neurotoxin beta-N-methylamino-L-alanine (BMAA). Dietary exposure to BMAA has been suggested to be involved in the etiology of the neurodegenerative disease amyotrophic lateral sclerosis/Parkinsonism-dementia complex (ALS/PDC). Little is known about BMAA-induced neurotoxicity following neonatal administration. Our previous studies have revealed an uptake of BMAA in the hippocampus and striatum of neonatal mice. Furthermore, rats treated with BMAA during the neonatal period displayed acute but transient motoric disturbances and failed to show habituation at juvenile age suggesting impairments in learning functions. In the present study, the aim was to investigate long-term behavioral effects of BMAA administration in neonatal rats. BMAA was administered on postnatal days 9-10 (200 or 600 mg/kg; subcutaneous injection). Spatial learning and memory was investigated in adulthood using the radial arm maze test. The results revealed impaired learning but not memory in BMAA-treated animals. The observed impairments were not due to alterations in motoric capacity, general activity, or behavioral profiles, as assessed in the multivariate concentric square field (MCSF) and open field tests. An aversive stimulus in the MCSF test revealed impairments in avoidance learning and/or memory. There was no difference in basal serum corticosterone levels in BMAA-treated animals, indicating that the observed long-term effects were not secondary to an altered basal hypothalamic-pituitary-adrenal axis function. The present data demonstrated long-term learning impairments following neonatal BMAA administration. Further studies on biochemical effects in various brain regions and subsequent behavioral alterations are needed to elucidate the mechanisms of BMAA-induced developmental neurotoxicity.

Transfer of a cyanobacterial neurotoxin within a temperate aquatic ecosystem suggests pathways for human exposure

“…Both free and proteinassociated BMAA also have been found in several tissue types, including brain, muscle, skin, intestine, kidney, and fur, in flying foxes (Pteropus mariannus and P. tonganus) (42). CNS uptake and long-term and short-term neurotoxic effects of BMAA have been demonstrated in rodents after perinatal administration (13,43). The mechanisms of entry to the CNS of BMAA remain unclear, however.…”

A Rank-Order Procedure Applied to an Ethoexperimental Behavior Model—The Multivariate Concentric Square Field<sup>TM </sup>(MCSF) Test

“…During the trial time of 20 min, the animal acquires experience of the experimental set-up that is manifested in the performance when repeatedly tested 40 -50 days after the first trial [11,20]. In addition, exposure to a presumed aversive air-puff resulted in longer latency in first visiting and fewer animals visiting the area associated with the air-puff when tested two weeks later [21].…”

Validation of an air-puff passive-avoidance paradigm for assessment of aversive learning and memory in rat models of chronic pain

“…The use of air-puff to induce avoidance responding and to evaluate cognition has been described previously Karlsson et al, 2009;Koistinaho et al, 2001). …”

“…Karlsson et al (2009) tested cognition in a multivariate concentric square-field paradigm, which was also used to investigate locomotor activity, exploration, risk assessment, risktaking and security-seeking. Air-puff was administered when rats entered a defined zone within the test apparatus.…”

“…A brief, non-noxious exposure to compressed air ("air-puff") applied to the head of a rodent induces fear-related behaviour such as a startle response (Engelmann et al, 1996), 22kHz ultrasonic vocalisation (Sanchez, 2003) and avoidance behaviour Karlsson et al, 2009;Koistinaho et al, 2001). Therefore, we hypothesised that the use of an air-puff stimulus may be a suitable non-noxious alternative to foot-shock in passiveavoidance paradigms designed to assess aversive memory in rodent models of chronic pain.…”