Role of the cholinergic system in the regulation of neurotrophin synthesis.
Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) are members of the family of neurotrophins that are highly expressed in the adult hippocampus, and to a lesser extent, in the cerebral cortex and olfactory bulb. Since neuronal expression of neutrophins is controlled by some neurotransmitters and there is a topographical correlation between neurotrophin expression and cholinergic terminal distribution from the cholinergic basal forebrain (CBF) neurons in these areas, the question arises as to whether the cholinergic system can also regulate neurotrophin gene expression in the CNS. When CBF neurons were selectively and completely destroyed by intraventricular injection of 192 IgG-saporin, resulting in a cholinergic deafferentation of the hippocampus, cortex, and olfactory bulb, there were no significant changes in NGF, BDNF and/or NT-3 mRNA levels in these areas from 1 week to 5 months after the lesion. These results suggest that afferents from CBF neurons may not play a significant role in maintaining basal levels of neurotrophin gene expression in the adult rat brain under physiological conditions. However, potential cholinergic regulation of brain neurontrophin expression may occur under other circumstances.
Yu
J
J
Department of Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston 77555-0652, USA.
Pizzo
D P
DP
Hutton
L A
LA
Perez-Polo
J R
JR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D018678:Cholinergic Agents / Q000494:pharmacology; D002799:Cholinergic Fibers / Q000502:physiology*; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D000922:Immunotoxins / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D009699:N-Glycosyl Hydrolases; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D009474:Neurons / Q000378:metabolism; D020933:Neurotrophin 3; D009830:Olfactory Bulb / Q000166:cytology / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D020917:Receptor, trkA; D011950:Receptors, Cholinergic / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000235:genetics; D012260:Ribonucleases; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D012680:Sensitivity and Specificity; D012686:Septal Nuclei / Q000166:cytology / Q000378:metabolism
C085696:192 IgG-saporin; D000911:Antibodies, Monoclonal; D019208:Brain-Derived Neurotrophic Factor; D018678:Cholinergic Agents; D000922:Immunotoxins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020933:Neurotrophin 3; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011950:Receptors, Cholinergic; D017475:Receptors, Nerve Growth Factor; D054789:Ribosome Inactivating Proteins, Type 1; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA; D012260:Ribonucleases; D009699:N-Glycosyl Hydrolases; D000076985:Saporins