Chronic administration of aluminum–fluoride or sodium–fluoride to rats in drinking water: alterations in neuronal and cerebrovascular integrity
Varner JA, Jensen KF, Horvath W, Isaacson RL. Brain Res. 1998 Feb 16;784(1-2):284-98. (See study)


This study describes alterations in the nervous system resulting from chronic administration of the fluoroaluminum complex (AlF3) or equivalent levels of fluoride (F) in the form of sodium–fluoride (NaF). Twenty seven adult male Long–Evans rats were administered one of three treatments for 52 weeks: the control group was administered double distilled deionized drinking water (ddw). The aluminum-treated group received ddw with 0.5 ppm AlF3 and the NaF group received ddw with 2.1 ppm NaF containing the equivalent amount of F as in the AlF3 ddw. Tissue aluminum (Al) levels of brain, liver and kidney were assessed with the Direct Current Plasma (DCP) technique and its distribution assessed with Morin histochemistry. Histological sections of brain were stained with hematoxylin & eosin (H&E), Cresyl violet, Bielschowsky silver stain, or immunohistochemically for b-amyloid, amyloid A, and IgM. No differences were found between the body weights of rats in the different treatment groups although more rats died in the AlF3 group than in the control group. The Al levels in samples of brain and kidney were higher in both the AlF3 and NaF groups relative to controls. The effects of the two treatments on cerebrovascular and neuronal integrity were qualitatively and quantitatively different. These alterations were greater in animals in the AlF3 group than in the NaF group and greater in the NaF group than in controls.


“A progressive general decline in appearance of the AlF3 animals was noted throughout the experiment. In addition
to the yellowing of the hair that occurs with age, the hair of animals in the AlF group became sparse revealing the underlying skin which was dry, flaky, and of a copper color. Although the body weights did not differ among the
groups, there was a greater number of deaths in the AlF3 group than in the control group…”

Fluoride increases aluminium accumulation in the brain

“The brains of the AlF and NaF groups had higher levels of Al compared to controls.”

“In all groups there were consistent treatment-related differences in the intensity and extent of Al-fluorescence.”

“Ratings by observers blind to the experimental groups confirmed the AlF group exhibited greater fluorescence in layer 6 of the left hemisphere than the controls.”

“Greater Al-fluorescence also occurred in layer 5 of the left hemisphere of the AlF3 group compared to the same region of brains from the NaF group and controls.”

“CA3 and CA4 regions of the hippocampus of the left hemisphere of the brains from the AlF3 group also exhibited increased fluorescence compared to controls.”

Damaged and abnormal cells in aluminium-containing brains

“In neocortical layers 2 and 3 of the right hemisphere, a significant difference was found between the AlF and the NaF groups. The AlF group had more moderately damaged cells than the NaF group which had more normal cells. In neocortical layers 2 and 3 of the left hemisphere, the AlF group had more abnormal cells than did controls.”

“In addition to differences in the frequency of abnormal neurons there were also differences between the treatment
groups in neuronal density in the hippocampus and neocortex. In the hippocampus, neuronal density was decreased
in area CA3 in the left hemisphere of the AlF group relative to controls.”

“There was a significant decrease in neuronal density of neocortical layers 2 and 3 in the left hemisphere of AlF group relative to the controls and to the NaF groups.”

“Significant reductions of cell density were found in layers 5 and 6 of the AlF group compared to controls in the left hemisphere.”

“In control animals, the localization of IgM was largely restricted to the vascular lumen, indicative of the integrity of the BBB to IgM. Staining of the neuronal parenchyma in the AlF and NaF groups was significantly increased in the right hemisphere.”

Differences in the amount of immunoreactivity for bamyloid
relative to that for amyloid A were most promi-
nent in the vasculature of the dorsal thalamus Figs. 11 and
12.. The control group had few instances of immunoreactivity
while the tissue of animals from the AlF group 3
demonstrated a bimodal distribution of reaction product—
the animals had an absence of reaction product staining or
a high level. A significant difference was found between
the AlF and the control group in the lateral posterior 3
thalamic areas in both hemispheres

The NaF group
also differed significantly from the control group in the
right lateral posterior thalamic area: the controls demonstrated
low immunoreactivity while rats in the NaF group
had either no or high levels of immunoreactivity


“The kidneys of the AlF group exhibited elevated Al levels compared to both the control and NaF groups.”

“In the kidney, glomerular hypercellularity and mesangial proliferation was apparent in animals from both the
NaF and AlF treatment groups.”

“Congruent with the glomerular changes was deposition of protein in the tubules.”

“There was a significant increase in the extent of monocyte infiltration in the animals treated with AlF compared to controls.”