Carrier mediated delivery of NGF: alterations in basal forebrain neurons in aged rats revealed using antibodies against low and high affinity NGF receptors.
The distribution of low and high affinity nerve growth factor (NGF) receptors was investigated in the basal forebrain during aging and NGF treatment. A peripheral administration model for NGF was utilized. NGF was conjugated to a transferrin receptor antibody (OX-26-NGF), and this conjugate was injected into the tail vein of aged Fischer 344 male rats (24 months) twice weekly for 5 weeks (equivalent to 50 microg of NGF/injection). Controls were injected with a non-conjugated mixture of OX-26 and NGF. The aged rats treated with conjugate showed a significant increase in cell size of p75- and trkA-immunoreactive neurons in the medial septal nucleus and vertical limb of the diagonal band as compared to controls. A significant increase in cell size of trkA-immunoreactive neurons was also observed in the horizontal limb of the diagonal band in rats treated with conjugate. Rats treated with conjugate also showed a significant increase in overall staining density for p75 and trkA antibodies in the medial septal nucleus as compared to controls. A significant increase in staining density of p75-immunoreactive structures was also observed in the vertical and horizontal limbs of the diagonal band. Therefore, treatment with OX-26-NGF conjugate has regional effects on both the low and high affinity NGF receptors in terms of cell body size and staining density in the basal forebrain of aged rats. The current findings support the idea that this delivery system might be useful in therapeutic approaches involving the delivery of neurotrophic factors and other large molecules into the brain.
Bäckman
C
C
Department of Basic Science, University of Colorado HSC, Denver 80262, USA.
Rose
G M
GM
Bartus
R T
RT
Hoffer
B J
BJ
Mufson
E J
EJ
Granholm
A C
AC
D000375:Aging / Q000473:pathology*; D000818:Animals; D000911:Antibodies, Monoclonal; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008297:Male; D009414:Nerve Growth Factors / Q000008:administration & dosage*; D009474:Neurons / Q000737:chemistry / Q000187:drug effects*; D016548:Prosencephalon / Q000166:cytology / Q000187:drug effects*; D011518:Proto-Oncogene Proteins / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000032:analysis*
D000911:Antibodies, Monoclonal; D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA