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The Journal of Neuroscience, November 15, 1999, 19(22):9687-9697

Functional Blockade of Tyrosine Kinase A in the Rat Basal Forebrain by a Novel Antagonistic Anti-Receptor Monoclonal Antibody

Antonino Cattaneo¹, Simona Capsoni¹, Elisa Margotti¹, Massimo Righi¹, Eva Kontsekova², Peter Pavlik², Peter Filipcik², and Michal Novak^{1, 2}

¹ Neuroscience Programme, International School for Advanced Studies, 34014 Trieste, Italy, and ² Institute of Neuroimmunology, Slovak Academy of Sciences, 842-46 Bratislava, Slovak Republic

We have exploited a new monoclonal antibody against the tyrosine kinase A (TrkA) nerve growth factor (NGF) receptor to block the NGF-TrkA interaction in the rat basal forebrain. The monoclonal antibody MNAC13 is a potent antagonist that prevents the binding of NGF to TrkA in a variety of systems. This antibody was used to study the maintenance of the cholinergic phenotype in the rat basal forebrain in vivo, by the implant of antibody-secreting cells. Basal forebrain cholinergic neurons (BFCNs) are greatly affected by the antibody treatment, both in terms of cell number and of cell soma size. When antibody-secreting cells are implanted at postnatal day 2 (P2), the effects observed at P8 are as severe as those obtained with anti-NGF antibodies and, interestingly, are observed also if anti-TrkA cells are implanted at P8, when anti-NGF antibodies, delivered by the same route, are no longer effective (Molnar et al., 1998). The effects induced by anti-TrkA, as those induced by anti-NGF, are reversible, but the time required for recovery and the critical period in the sensitivity of BFCNs to the functional inactivation of TrkA is twice as long than that observed when NGF is intercepted. These results demonstrate that BFCNs are more sensitive to the block of TrkA activation than they are to the block of NGF. The cloning of MNAC13 variable regions and their assembly into a functional polypeptide of reduced size (single chain Fv fragment) will allow its use in gene transfer applications.

Key words: TrkA; NGF receptors; antagonist monoclonal antibody; basal forebrain cholinergic neurons; recombinant antibody fragment; rat

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Copyright © 1999 Society for Neuroscience  0270-6474/99/19229687-11$05.00/0

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				G. Ugolini, S. Marinelli, S. Covaceuszach, A. Cattaneo, and F. Pavone The function neutralizing anti-TrkA antibody MNAC13 reduces inflammatory and neuropathic pain PNAS, February 20, 2007; 104(8): 2985 - 2990. [Abstract] [Full Text] [PDF]

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