Department of Biochemistry and Microbiology, Nelson Mandela University, P.O. Box 77 000, Port Elizabeth 6031, South Africa.
Toxins (Basel). 2017 Dec 27;10(1):16. doi: 10.3390/toxins10010016.
Cyanobacterial β--methylamino--alanine (BMAA) has been suggested as a causative or contributory factor in the development of several neurodegenerative diseases. However, no BMAA animal model has adequately shown clinical or behavioral symptoms that correspond to those seen in either Alzheimer's Disease (AD), Amyotrophic Lateral Sclerosis (ALS) or Parkinson's Disease (PD). We present here the first data that show that when neonatal rats were exposed to BMAA on postnatal days 3, 4 and 5, but not on gestational day 14 or postnatally on days 7 or 10, several AD and/or PD-related behavioral, locomotor and cognitive deficits developed. Male rats exhibited severe unilateral hindlimb splay while whole body tremors could be observed in exposed female rats. BMAA-exposed rats failed to identify and discriminate a learned odor, an early non-motor symptom of PD, and exhibited decreased locomotor activity, decreased exploration and increased anxiety in the open field test. Alterations were also observed in the rats' natural passive defense mechanism, and potential memory deficits and changes to the rat's natural height avoidance behavior could be observed as early as PND 30. Spatial learning, short-term working, reference and long-term memory were also impaired in 90-day-old rats that had been exposed to a single dose of BMAA on PND 3-7. These data suggest that BMAA is a developmental neurotoxin, with specific target areas in the brain and spinal cord.
蓝藻衍生的β-甲基氨基-L-丙氨酸（BMAA）被认为是几种神经退行性疾病发展的原因或促成因素。然而，没有任何 BMAA 动物模型充分显示出与阿尔茨海默病（AD）、肌萎缩侧索硬化症（ALS）或帕金森病（PD）中所见相符的临床或行为症状。我们在此首次提供的数据表明，当新生大鼠在出生后第 3、4 和 5 天接触 BMAA，但不在妊娠第 14 天或出生后第 7 或 10 天接触时，会出现几种 AD 和/或 PD 相关的行为、运动和认知缺陷。雄性大鼠表现出严重的单侧后肢伸展，而暴露的雌性大鼠则可观察到全身震颤。接触 BMAA 的大鼠无法识别和区分已习得的气味，这是 PD 的早期非运动症状，并且在旷场试验中表现出运动活性降低、探索减少和焦虑增加。大鼠的自然被动防御机制也发生了改变，在 PND 30 时就可以观察到潜在的记忆缺陷和大鼠自然高度回避行为的变化。在出生后第 3-7 天接受单剂量 BMAA 暴露的 90 天大鼠中，空间学习、短期工作、参考和长期记忆也受损。这些数据表明，BMAA 是一种发育神经毒素，在大脑和脊髓中有特定的靶区。
