PMID- 10632606
OWN - NLM
STAT- MEDLINE
DCOM- 20000209
LR  - 20240420
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 20
IP  - 2
DP  - 2000 Jan 15
TI  - BDNF promotes the regenerative sprouting, but not survival, of injured 
      serotonergic axons in the adult rat brain.
PG  - 771-82
AB  - Brain-derived neurotrophic factor (BDNF) has trophic effects on serotonergic 
      (5-HT) neurons in the adult brain and can prevent the severe loss of cortical 
      5-HT axons caused by the neurotoxin p-chloroamphetamine (PCA). However, it has 
      not been determined whether BDNF promotes the survival of 5-HT axons during 
      PCA-insult or facilitates their regenerative sprouting after injury. We show here 
      that BDNF fails to protect most 5-HT axons from PCA-induced degeneration. 
      Instead, chronic BDNF infusions markedly stimulate the sprouting of both intact 
      and PCA-lesioned 5-HT axons, leading to a hyperinnervation at the neocortical 
      infusion site. BDNF treatment promoted the regrowth of 5-HT axons when initiated 
      up to a month after PCA administration. The sprouted axons persisted in cortex 
      for at least 5 weeks after terminating exogenous BDNF delivery. BDNF also 
      encouraged the regrowth of the 5-HT plexus in the hippocampus, but only in those 
      lamina where 5-HT axons normally ramify. In addition, intracortical BDNF 
      infusions induced a sustained local activation of the TrkB receptor. The 
      dose-response profiles for BDNF to stimulate 5-HT sprouting and Trk signaling 
      were remarkably similar, suggesting a physiological link between the two events; 
      both responses were maximal at intermediate doses of BDNF but declined at higher 
      doses ("inverted-U-shaped" dose-response curves). Underlying the downregulation 
      of the Trk signal with excessive BDNF was a decline in full-length TrkB protein, 
      but not truncated TrkB protein or TrkB mRNA levels. Thus, BDNF-TrkB signaling 
      does not protect 5-HT neurons from axonal injury, but has a fundamental role in 
      promoting the structural plasticity of these neurons in the adult brain.
FAU - Mamounas, L A
AU  - Mamounas LA
AD  - Department of Pathology (Division of Neuropathology), The Johns Hopkins 
      University School of Medicine, Baltimore, Maryland 21205, USA. 
      Mamounas@welchkink.welch.jhu.edu
FAU - Altar, C A
AU  - Altar CA
FAU - Blue, M E
AU  - Blue ME
FAU - Kaplan, D R
AU  - Kaplan DR
FAU - Tessarollo, L
AU  - Tessarollo L
FAU - Lyons, W E
AU  - Lyons WE
LA  - eng
GR  - F32 MH085433/MH/NIMH NIH HHS/United States
GR  - R29MH85433/MH/NIMH 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 (Neurotoxins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
RN  - 333DO1RDJY (Serotonin)
RN  - 64-12-0 (p-Chloroamphetamine)
RN  - EC 2.7.10.1 (Receptor, trkA)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Axons/drug effects/pathology/*physiology
MH  - Brain-Derived Neurotrophic Factor/administration & dosage/*pharmacology
MH  - Cell Survival/drug effects
MH  - Cerebral Cortex/*drug effects/pathology/physiology
MH  - Functional Laterality
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Infusions, Parenteral
MH  - Male
MH  - Nerve Regeneration/drug effects/*physiology
MH  - Neurotoxins/toxicity
MH  - RNA, Messenger/genetics
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, trkA/genetics/metabolism
MH  - Receptor, trkB/genetics/metabolism
MH  - Recombinant Proteins/administration & dosage/pharmacology
MH  - Serotonin/*physiology
MH  - Time Factors
MH  - Transcription, Genetic/drug effects
MH  - p-Chloroamphetamine/*toxicity
PMC - PMC6772430
EDAT- 2000/01/13 00:00
MHDA- 2000/01/13 00:01
PMCR- 2000/07/15
CRDT- 2000/01/13 00:00
PHST- 2000/01/13 00:00 [pubmed]
PHST- 2000/01/13 00:01 [medline]
PHST- 2000/01/13 00:00 [entrez]
PHST- 2000/07/15 00:00 [pmc-release]
AID - 3804 [pii]
AID - 10.1523/JNEUROSCI.20-02-00771.2000 [doi]
PST - ppublish
SO  - J Neurosci. 2000 Jan 15;20(2):771-82. doi: 10.1523/JNEUROSCI.20-02-00771.2000.