Two peptides derived from the nerve growth factor precursor enhance cholinergic enzyme activities in vivo

LIP1, a 29-amino acid (aa) peptide, and LIP2, a 38aa peptide, corresponding to sequences within the nerve growth factor (NGF) precursor that are flanked by basic amino acid processing sites, were shown to be present in the rat intestine and to induce in PC12 cells several early cellular events, such as F-actin rearrangement and tyrosine phosphorylation of the Trk protein. In this report, we provide evidence that the two propeptides can affect cholinergic enzyme activities in vivo. Intracerebroventricular injections of LIP1 or LIP2 in neonatal hypothyroid rats significantly increased choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities in forebrain regions with an apparent regional specificity. Moreover, antibodies against LIP1 or LIP2 injected intracerebroventricularly in neonatal rats significantly decreased ChAT and AChE in the same regions of the brain. These data suggest a physiological role for the two propeptides derived from the proNGF in the development of forebrain cholinergic neurons.