Aluminum induces neurite elongation and sprouting in cultured hippocampal neurons

It has been reported that the aluminum content in the human brain increases with age, and it is particularly high in those with Alzheimer's disease. In this study, we found that a low aluminum concentration (100 mumol/L) in the culture media of opossum hippocampal neurons can induce extensive neurite outgrowth (ie, elongation and branching of neurites) and sprouting (ie, outgrowth of filiform processes from neurite varicosities) within 48 hours. Such changes in neurite morphology were remarkably similar to those described in the aged or Alzheimer's disease brain. Neurites that responded to aluminum varied greatly in length, thickness, and branching pattern. Many neurites appeared to have no clear directional growth pattern because they frequently changed their course and formed a meshwork of neurites with others originating from the same cell body. Sprouting neurites varied in length, thickness, and branching pattern, but they always originated from a globular enlargement of neurites along the neurite shaft or at the terminal end. Such growth pattern and extensive sprouting of neurites did not fit the growth pattern displayed by the control neurons. Our findings suggest that aluminum may be involved in the neuronal remodeling characteristic of aging and Alzheimer's disease.