Neurotrophin-evoked rapid excitation through TrkB receptors

Abstract

Neurotrophins are a family of structurally related proteins that regulate the survival, differentiation and maintenance of function of different populations of peripheral and central neurons. They are also essential for modulating activity-dependent neuronal plasticity. Here we show that neurotrophins elicit action potentials in central neurons. Even at low concentrations, brain-derived neurotrophic factor (BDNF) excited neurons in the hippocampus, cortex and cerebellum. We found that BDNF and neurotrophin-4/5 depolarized neurons just as rapidly as the neurotransmitter glutamate, even at a more than thousand-fold lower concentration. Neurotrophin-3 produced much smaller responses, and nerve growth factor was ineffective. The neurotrophin-induced depolarization resulted from the activation of a sodium ion conductance which was reversibly blocked by K-252a, a protein kinase blocker which prefers tyrosine kinase Trk receptors. Our results demonstrate a very rapid excitatory action of neurotrophins, placing them among the most potent endogenous neuro-excitants in the mammalian central nervous system described so far.

Exercise reverses the harmful effects of consumption of a high-fat diet on synaptic and behavioral plasticity associated to the action of brain-derived neurotrophic factor

“…BDNF holds a well-established protective role in the adult brain such that genetic deletion of the BDNF gene in mice increases the incidence of apoptosis (Linnarsson et al, 1997). The expression of BDNF in the hippocampus is elevated by exercise (Neeper et al, 1995), in line with recent studies showing a clear involvement of BDNF with regulation of neuronal excitability (Kafitz et al, 1999;Bolton et al, 2000). BDNF is synthesized predominantly by neurons located in the hippocampus, a brain region intimately associated with the processing of cognitive function (Wetmore et al, 1991).…”

The Corticosteroid Receptor Hypothesis of Depression

“…Because long-term administration of moclobemide suppresses HPA activity and activates cAMP-mediated CREB phosphorylation via PKA, the expression of BDNF may be enhanced and followed by a profound alteration in synaptic efficiency (Korte et al 1995(Korte et al , 1996Chen et al 1999;Kafitz et al 1999). Furthermore, in these transgenic mice, morphine-induced mesolimbic release of serotonin and dopamine as well as the psychomotor-stimulant effects of morphine were enhanced.…”

Is it time to reassess the BDNF hypothesis of depression?

“…2,3 This theory has directed research away from monoamines and towards the putative role of growth factors such as brain-derived neurotrophic factor (BDNF), known to be critically involved in regulating neural structure and plasticity in the adult brain. 4,5 The neurotrophin hypothesis postulates that a loss of BDNF plays a major role in the pathophysiology of depression, and that its restoration may represent a critical mechanism underlying antidepressant efficacy. This theory has received considerable support and led to major investigation into the potential of BDNF as a novel target for antidepressant treatment.…”