Distribution and levels of insulin-like growth factor (IGF-I and IGF-II) and insulin receptor binding sites in the spinal cords of amyotrophic lateral sclerosis (ALS) patients.
The structurally related peptides, insulin and insulin-like growth factors (IGF-I and IGF-II), have neurotrophic properties and potentially could be of therapeutic value in human neurodegenerative disorders. In this study, we compared the anatomical distribution of [125I]IGF-I, [125I]IGF-II and [125I]insulin binding sites in thoracic spinal cords from patients who died of amyotrophic lateral sclerosis (ALS) and normal controls. For these three ligands, the greatest amounts of specific binding were located in the deeper layers of the dorsal horn > intermediate zone > lamina X > ventral horn > superficial layers of the dorsal horn > white matter of the spinal cord. Highly significant (P < 0.001) increases in the density of [125I]IGF-I and [125I]IGF-II binding were apparent in various laminae of the cord of ALS patients with increased binding being particularly evident in the ventral horn and the intermediate zone. Significant (P < 0.05) increases were also seen in lamina X and in the dorsal horn. In contrast, no significant differences in [125I]insulin binding were observed between ALS and control spinal cords. Taken together, these data reveal significant increases in both [125I]IGF-I and [125I]IGF-II binding levels in the spinal cords of ALS patients albeit to different extents. These findings may be of relevance for future therapeutic strategies aimed at slowing the progression of this chronic neurodegenerative disease, as recently suggested by the beneficial therapeutic effects of an IGF-I treatment in ALS patients.
Doré
S
S
Douglas Hospital Research Centre, Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
Krieger
C
C
Kar
S
S
Quirion
R
R
D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007328:Insulin / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D007335:Insulin-Like Growth Factor II / Q000502:physiology; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000032:analysis*; D017526:Receptor, IGF Type 1 / Q000032:analysis*; D017527:Receptor, IGF Type 2 / Q000032:analysis*; D011972:Receptor, Insulin / Q000032:analysis*; D013116:Spinal Cord / Q000737:chemistry*
D007328:Insulin; D009419:Nerve Tissue Proteins; D017527:Receptor, IGF Type 2; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin