Distribution of radioiodinated recombinant human nerve growth factor in primate brain following intracerebroventricular infusion.
The distribution of radioiodinated recombinant human nerve growth factor ([125I]rhNGF) was evaluated in adult cynomolgus monkeys following unilateral intracerebroventricular (icv) administration. Animals were cannulated into the right ventricle and recovered for 7 days. Monkeys were infused with 1.2 micrograms of [125I]rhNGF or [125I]rhNGF with a 140-fold excess of rhNGF. Twenty-four hours after infusion, animals were anesthetized and transcardially perfused with an aldehyde fixative. Coronal brain sections were processed for quantitative film autoradiography or for choline-acetyltransferase immunohistochemistry and then emulsion dipped. Specific radiolabel was distributed bilaterally and, with equal density, throughout the basal forebrain and was colocalized with choline acetyltransferase-positive neurons. Specific labeling was also present in the superficial ventral cortex. Nonspecific binding was observed surrounding the ventricles and lining blood vessels. These results demonstrate that unilateral icv infusion is an effective approach for delivering NGF to basal forebrain cholinergic neurons in primates and represents a viable drug delivery strategy for the therapeutic use of NGF in Alzheimer's Disease.
Emmett
C J
CJ
Department of Neurobiology, Roche Bioscience, Palo Alto, California 94303, USA.
Stewart
G R
GR
Johnson
R M
RM
Aswani
S P
SP
Chan
R L
RL
Jakeman
L B
LB
D000818:Animals; D001345:Autoradiography; D001923:Brain Chemistry / Q000502:physiology*; D002421:Caudate Nucleus / Q000737:chemistry / Q000201:enzymology; D002552:Cerebral Ventricles / Q000737:chemistry; D002795:Choline O-Acetyltransferase / Q000032:analysis; D006801:Humans; D007276:Injections, Intraventricular; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008252:Macaca fascicularis; D009414:Nerve Growth Factors / Q000032:analysis / Q000493:pharmacokinetics*; D016548:Prosencephalon / Q000737:chemistry / Q000201:enzymology; D011994:Recombinant Proteins / Q000032:analysis / Q000493:pharmacokinetics
D007457:Iodine Radioisotopes; D009414:Nerve Growth Factors; D011994:Recombinant Proteins; D002795:Choline O-Acetyltransferase