| Title : A nerve growth factor mimetic TrkA antagonist causes withdrawal of cortical cholinergic boutons in the adult rat - Debeir_1999_Proc.Natl.Acad.Sci.U.S.A_96_4067 |
| Author(s) : Debeir T , Saragovi HU , Cuello AC |
| Ref : Proc Natl Acad Sci U S A , 96 :4067 , 1999 |
| Abstract : Cholinergic neurons respond to the administration of nerve growth factor (NGF) in vivo with a prominent and selective increase of choline acetyl transferase activity. This suggests the possible involvement of endogenous NGF, acting through its receptor TrkA, in the maintenance of central nervous system cholinergic synapses in the adult rat brain. To test this hypothesis, a small peptide, C(92-96), that blocks NGF-TrkA interactions was delivered stereotactically into the rat cortex over a 2-week period, and its effect and potency were compared with those of an anti-NGF monoclonal antibody (mAb NGF30). Two presynaptic antigenic sites were studied by immunoreactivity, and the number of presynaptic sites was counted by using an image analysis system. Synaptophysin was used as a marker for overall cortical synapses, and the vesicular acetylcholine transporter was used as a marker for cortical cholinergic presynaptic sites. No significant variations in the number of synaptophysin-immunoreactive sites were observed. However, both mAb NGF30 and the TrkA antagonist C(92-96) provoked a significant decrease in the number and size of vesicular acetylcholine transporter-IR sites, with the losses being more marked in the C(92-96) treated rats. These observations support the notion that endogenously produced NGF acting through TrkA receptors is involved in the maintenance of the cholinergic phenotype in the normal, adult rat brain and supports the idea that NGF normally plays a role in the continual remodeling of neural circuits during adulthood. The development of neurotrophin mimetics with antagonistic and eventually agonist action may contribute to therapeutic strategies for central nervous system degeneration and trauma. |
| ESTHER : Debeir_1999_Proc.Natl.Acad.Sci.U.S.A_96_4067 |
| PubMedSearch : Debeir_1999_Proc.Natl.Acad.Sci.U.S.A_96_4067 |
| PubMedID: 10097164 |
Debeir T, Saragovi HU, Cuello AC (1999)
A nerve growth factor mimetic TrkA antagonist causes withdrawal of cortical cholinergic boutons in the adult rat
Proc Natl Acad Sci U S A
96 :4067
Debeir T, Saragovi HU, Cuello AC (1999)
Proc Natl Acad Sci U S A
96 :4067