Neurobehavioral toxic effects of perinatal oral exposure to aluminum on the developmental motor reflexes, learning, memory and brain neurotransmitters of mice offspring

Pharmacol Biochem Behav. 2012 Mar;101(1):49-56. doi: 10.1016/j.pbb.2011.11.003. Epub 2011 Nov 13.


Aluminum (Al) is a known neurotoxicant and circumstantial evidence has linked this metal with several neurodegenerative disorders like Alzheimer's disease, but no causal relationship has yet been proved. Al-induced behavioral alterations as well as cognitive deficits and rodent brain neurotransmitter level, are well known in adults but the exact mechanism in the offspring of perinatally Al exposed dams is not yet understood properly and needs more attention. In the present study, the perinatal oral exposure of the dams to 300 and 600mg/kg/day Al (aluminum chloride) resulted in significant and deleterious effects in the offspring inflicting a dose-dependent reduction in postnatal body weight gain, delays in opening of the eyes and appearance of body hair fuzz, and deficits in the sensory motor reflexes of the mice pups during weaning period (from the day of birth to postnatal day 21). During adolescent ages of the male offspring, a significant and dose-dependent deficit was also observed in their locomotor activity at postnatal day 22 (PD 22), learning capability (at PD 25), and cognitive behavior (at PD 30-36). Furthermore, a significant and dose-dependent disturbance in the levels of neurotransmitters like dopamine (DA) and serotonin (5-HT) was also observed in the forebrain region of the offspring at PD 7, PD 14, PD 21, PD 30, and PD 36. Thus, perinatal Al exposure, particularly during pregnancy and lactation period, can affect the in utero developing fetus and postnatal developing sucklings, raising the concerns that during a critical perinatal period of brain development, Al exposure has potential and long lasting neurotoxic hazards and might modify the properties of the dopaminergic system and thus can change the threshold of that system or other related systems at later ages. A reduced use of Al during pregnancy is of crucial importance in preventing Al-induced delayed neurotoxicity in the offspring.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology
  • Aluminum / administration & dosage
  • Aluminum / toxicity*
  • Animals
  • Avoidance Learning / drug effects
  • Behavior, Animal / drug effects*
  • Biogenic Monoamines / metabolism
  • Body Weight / drug effects
  • Brain Chemistry / drug effects*
  • Dose-Response Relationship, Drug
  • Eye / growth & development
  • Female
  • Hair / drug effects
  • Learning / drug effects*
  • Male
  • Maze Learning / drug effects
  • Memory / drug effects*
  • Mice
  • Motor Activity / drug effects
  • Neurotoxicity Syndromes / metabolism
  • Neurotoxicity Syndromes / physiopathology*
  • Neurotoxicity Syndromes / psychology*
  • Neurotransmitter Agents / metabolism*
  • Pregnancy
  • Prenatal Exposure Delayed Effects
  • Reflex / drug effects*
  • Rotation


  • Biogenic Monoamines
  • Neurotransmitter Agents
  • Aluminum