PMID- 8613731 OWN - NLM STAT- MEDLINE DCOM- 19960606 LR - 20191101 IS - 0270-6474 (Print) IS - 1529-2401 (Electronic) IS - 0270-6474 (Linking) VI - 15 IP - 12 DP - 1995 Dec TI - Brain-derived neurotrophic factor promotes the survival and sprouting of serotonergic axons in rat brain. PG - 7929-39 AB - A pathology of brain serotonergic (5-HT) systems has been found in psychiatric disturbances, normal aging and in neurodegenerative disorders including Alzheimer's and Parkinson's disease. Despite the clinical importance of 5-HT, little is known about the endogenous factors that have neurotrophic influences upon 5-HT neurons. The present study examined whether chronic pain parenchymal administration of the neurotrophins brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) or NGF could prevent the severe degenerative loss of serotonergic axons normally caused by the selective 5-HT neurotoxin p-chloroamphetamine (PCA). The neurotrophins (5-12 micrograms/d) or the control substances (cytochrome c or PBS vehicle) were continuously infused into the rat frontoparietal cortex using an osmotic minipump. One week later, rats were subcutaneously administered PCA (10 mg/kg) or vehicle, and the 5-HT innervation was evaluated after two more weeks of neurotrophin infusion. As revealed with 5-HT immunocytochemistry, BDNF infusions into the neocortex of intact (non-PCA-lesioned) rats caused a substantial increase in 5-HT axon density in a 3 mm diameter region surrounding the cannula tip. In PCA-lesioned rats, intracortical infusions of BDNF completely prevented the severe neurotoxin-induced loss of 5-HT axons near the infusion cannula. In contrast, cortical infusions of vehicle or the control protein cytochrome c did not alter the density of serotonergic axons in intact animals, nor did control infusions prevent the loss of 5-HT axons in PCA-treated rats. NT-3 caused only a modest sparing of the 5-HT innervation in PCA-treated rats, and NGF failed to prevent the loss of 5-HT axon density. The immunocytochemical data were supported by neurochemical evaluations which showed that BDNF attenuated the PCA-induced loss of 5-HT and 5-HIAA contents and 3H-5-HT uptake near the infusion cannula. Thus, BDNF can promote the sprouting of mature, uninjured serotonergic axons and dramatically enhance the survival or sprouting of 5-HT axons normally damaged by the serotonergic neurotoxin PCA. FAU - Mamounas, L A AU - Mamounas LA AD - Laboratory of Cellular and Molecular Biology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. FAU - Blue, M E AU - Blue ME FAU - Siuciak, J A AU - Siuciak JA FAU - Altar, C A AU - Altar CA LA - eng GR - NS29167/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Nerve Growth Factors) RN - 0 (Nerve Tissue Proteins) RN - 0 (Neurotrophin 3) RN - 333DO1RDJY (Serotonin) RN - 54-16-0 (Hydroxyindoleacetic Acid) RN - 64-12-0 (p-Chloroamphetamine) SB - IM MH - Animals MH - Axons/*physiology MH - Brain/*cytology/*drug effects/physiology MH - Brain-Derived Neurotrophic Factor MH - Cell Survival/drug effects MH - Hydroxyindoleacetic Acid/metabolism MH - Immunohistochemistry MH - Male MH - Nerve Growth Factors/pharmacology MH - Nerve Regeneration/*drug effects MH - Nerve Tissue Proteins/*pharmacology MH - Neurotrophin 3 MH - Rats MH - Rats, Sprague-Dawley MH - Serotonin/*metabolism/pharmacokinetics MH - p-Chloroamphetamine/pharmacology PMC - PMC6577955 EDAT- 1995/12/01 00:00 MHDA- 1995/12/01 00:01 PMCR- 1996/06/01 CRDT- 1995/12/01 00:00 PHST- 1995/12/01 00:00 [pubmed] PHST- 1995/12/01 00:01 [medline] PHST- 1995/12/01 00:00 [entrez] PHST- 1996/06/01 00:00 [pmc-release] AID - 10.1523/JNEUROSCI.15-12-07929.1995 [doi] PST - ppublish SO - J Neurosci. 1995 Dec;15(12):7929-39. doi: 10.1523/JNEUROSCI.15-12-07929.1995.