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Titolo:
BDNF promotes the regenerative sprouting, but not survival, of injured serotonergic axons in the adult rat brain
Autore:
Mamounas, LA; Altar, CA; Blue, ME; Kaplan, DR; Tessarollo, L; Lyons, WE;
Indirizzi:
Johns Hopkins Univ, Sch Med, Dept Pathol, Div Neuropathol, Baltimore, MD 21205 USA Johns Hopkins Univ Baltimore MD USA 21205 pathol, Baltimore, MD 21205 USA Otsuka Amer Pharmaceut Inc, Global Neurosci Res, Rockville, MD 20850 USA Otsuka Amer Pharmaceut Inc Rockville MD USA 20850 Rockville, MD 20850 USA Johns Hopkins Univ, Sch Med, Kennedy Krieger Res Inst, Baltimore, MD 21205USA Johns Hopkins Univ Baltimore MD USA 21205 es Inst, Baltimore, MD 21205USA Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA Johns Hopkins Univ Baltimore MD USA 21205 Neurol, Baltimore, MD 21205 USA McGill Univ, Montreal Neurol Inst, Dept Neurol & Neurosurg, Montreal, PQ H3A 2B4, Canada McGill Univ Montreal PQ Canada H3A 2B4 surg, Montreal, PQ H3A 2B4, Canada NCI, Neural Dev Grp, Adv Biosci Labs,Basic Res Program, Frederick Canc Res& Dev Ctr, Frederick, MD 21702 USA NCI Frederick MD USA 21702 ick Canc Res& Dev Ctr, Frederick, MD 21702 USA
Titolo Testata:
JOURNAL OF NEUROSCIENCE
fascicolo: 2, volume: 20, anno: 2000,
pagine: 771 - 782
SICI:
0270-6474(20000115)20:2<771:BPTRSB>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
NERVE GROWTH-FACTOR; TRK PROTOONCOGENE PRODUCT; NEUROTROPHIC FACTOR BDNF; MESSENGER-RNA; ANTEROGRADE TRANSPORT; HIPPOCAMPAL-FORMATION; RETROGRADE TRANSPORT; SPINAL-CORD; IN-VIVO; INFUSION;
Keywords:
neurotrophin; BDNF; TrkB; serotonin; structural plasticity; sprouting; cerebral cortex; neurotoxicity; amphetamines; p-chloroamphetamine;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
65
Recensione:
Indirizzi per estratti:
Indirizzo: Mamounas, LA Johns Hopkins Univ, Sch Med, Dept Pathol, Div Neuropathol, 558 Ross Bldg,720 Rutland Ave, Baltimore, MD 21205 USA Johns Hopkins Univ 558Ross Bldg,720 Rutland Ave Baltimore MD USA 21205
Citazione:
L.A. Mamounas et al., "BDNF promotes the regenerative sprouting, but not survival, of injured serotonergic axons in the adult rat brain", J NEUROSC, 20(2), 2000, pp. 771-782

Abstract

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 atintermediate 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.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 24/11/20 alle ore 23:49:39