Cellular and Molecular Neurobiology

, Volume 14, Issue 6, pp 791–808

Studies of aluminum neurobehavioral toxicity in the intact mammal

  • Robert A. Yokel
  • David D. Allen
  • Jerome J. Meyer

DOI: 10.1007/BF02088685

Cite this article as:
Yokel, R.A., Allen, D.D. & Meyer, J.J. Cell Mol Neurobiol (1994) 14: 791. doi:10.1007/BF02088685


1. Aluminum (Al) has been implicated in neurotoxic syndromes in several conditions, including Alzheimer's disease (AD). The developmental stage of the mammalian brain most susceptible to Al was determined in rabbits systemically exposed to Al during the prenatal, postnatal, or second month or for 1 month as adults or as aged subjects. Eyeblink reflex classical conditioning showed an Al-induced learning deficit only in the adult and aged rabbits.

2. 4-Aminopyridine, which was reported to improve learning in AD subjects, attenuated this Al-induced learning deficit.

3. Conditioned eyeblink acquisition is slower in AD subjects than controls, supporting the Al-loaded rabbit as a model of some AD effects.

4. To determine if the Al-loaded rabbit modeled the AD cholinergic deficit, acetylcholine (Ach) overflow was measured in rabbit hippocampus using microdialysis. Aluminum pretreatment reduced basal and potassium-stimulated Ach overflow compared to controls.

5. Acetylcholine overflow increased as control rabbits acquired the conditioned eyeblink reflex, then subsequently decreased, although conditioned eyeblink performance continued. In contrast, Al-loaded rabbits showed a delay in conditioned eyeblink acquisition and greatly attenuated Ach overflow. The Al-induced attenuation of Ach overflow may contribute to the Al-induced learning deficit.

6. Brain Al entry was studied using microdialysis of blood, brain, and lateral ventricle. Aluminum rapidly entered the brain and lateral ventricle. Frontal cortical Al was greater than lateral ventricular Al, suggesting that Al primarily enters the brain through the cerebral microvasculature.

7. The brain/blood Al ratio was always significantly less than 1. This ratio was influenced by the Al form administered, brain site and animal species. Thus, there appears to be an active process moving Al out of brain extracellular fluid (ECF).

8. Brain and blood dialysate Ach concentrations were not different after cyanide addition to the dialysate, supporting the conclusion that an active process moves Al out of brain ECF.

Key words

acetylcholinealuminumblood-brain barrierclassical conditioninglearningmicrodialysisrabbitrat

Copyright information

© Plenum Publishing Corporation 1994

Authors and Affiliations

  • Robert A. Yokel
    • 1
    • 2
  • David D. Allen
    • 1
  • Jerome J. Meyer
    • 1
  1. 1.Division of Pharmacology & Experimental Therapeutics, College of PharmacyUniversity of KentuckyLexington
  2. 2.Graduate Center for ToxicologyUniversity of KentuckyLexington
  3. 3.Laboratory of Neurosciences, National Institute on AgingNational Institutes of HealthBethesda