Prenatal Exposure of Mice to Beta‐methyl‐amino‐L‐alanine (BMAA) as a Model for Amyotrophic Lateral Sclerosis‐Parkinson’s Dementia Complex (ALS‐PDC).

Amyotrophic Lateral Sclerosis‐Parkinson’s Dementia Complex (ALS‐PDC) is a severe neurological disorder, caused by degeneration of upper motor glutamine (UMG), nigrostriatal dopamine (NSDA) and basal forebrain acetylcholine (BFbA) neurons, and locally called Lytico‐bodig in Guam. The incidence of ALS‐PDC has decline, but the cause is still unknown. Several studies indicate that beta‐methylamino‐L‐alanine (BMAA), a non‐protein amino acid, consumed in food prepared from the cycad plant, is the cause of ALS‐PDC. The consumption of BMAA has been reduced, as well as the incidence of ALS‐PDC, and these implicate BMAA as a likely cause for ALS‐PDC, Studies, however, had produced no good model of ALS‐PDC. Since UMG, NSDA and MFbA neurons are impaired in ALS‐PDC, we targeted these neuronal groups in the fetus, by exposing C57BL/6J pregnant mice to BMAA during gestation day 8–18, the birth or neurogenesis of these neurons in the fetus. The goal was to produce impaired neurons that will succumb/die early during aging. The outcomes showed post‐natal changes in weight, behaviors, muscle functions as well as specific neurotransmitters and other neurochemicals. BMAA administered at 10, 50 and 100 mg/kg to the pregnant dams caused dose‐dependent reduction in the weight of two weeks pups by 12.5, 20.0 and 27.5% of the control. Body weight, however, recovered at 4–5 weeks post‐weaning. Prenatal BMAA also reduced open field motor activity: e.g. the total distance travelled was reduced by 8.8, 11.6 and 19% by the respective doses of BMAA. On the Rota‐Rod, the latency to fall was dramatically reduced to 71.4, 17.4 and 8.7% by the 10, 50 and 100 mg/kg of prenatal BMAA, as compared to control. Likewise, the no of revolution per min that the mice endured were reduced from the control value of 100%, to 67.8%, 25.4% and 16.9% for the 10, 50 and 100 mg/kg of BMAA. The data show that BMAA has effects on motor performance of offspring exposed prenatally. The continuation of the study will reveal underlying neurochemical changes that may be related to ALS‐PDC. The indication is that ALSPDC may have a fetal basis in which early subtle neuronal impairments occurred and symptoms precipitated later in life when UMN, NSDA and MFbA are impaired during aging. Support or Funding Information NIH