Brain-derived neurotrophic factor promotes the survival and sprouting of serotonergic axons in rat brain.

Abstract

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.

• Authors: L A Mamounas, M E Blue, J A Siuciak, C A Altar
• Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 15 Issue 12 Pg. 7929-39 (Dec 1995) ISSN: 0270-6474 [Print] United States
• PMID: 8613731 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Brain-Derived Neurotrophic Factor
• Nerve Growth Factors
• Nerve Tissue Proteins
• Neurotrophin 3
• Serotonin
• Hydroxyindoleacetic Acid
• p-Chloroamphetamine

Topics

• Animals
• Axons (physiology)
• Brain (cytology, drug effects, physiology)
• Brain-Derived Neurotrophic Factor
• Cell Survival (drug effects)
• Hydroxyindoleacetic Acid (metabolism)
• Immunohistochemistry
• Male
• Nerve Growth Factors (pharmacology)
• Nerve Regeneration (drug effects)
• Nerve Tissue Proteins (pharmacology)
• Neurotrophin 3
• Rats
• Rats, Sprague-Dawley
• Serotonin (metabolism, pharmacokinetics)
• p-Chloroamphetamine (pharmacology)