Altered expression of BDNF and its high-affinity receptor TrkB in response to complex motor learning and moderate exercise

Klintsova, Anna Y.; Dickson, Elizabeth; Yoshida, Rie; Greenough, William T.

doi:10.1016/j.brainres.2004.09.003

Cited by 158 publications

(106 citation statements)

References 84 publications

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“…In the hippocampus in vivo, BNDF is rapidly and selectively induced after contextual learning (Hall et al, 2000). BDNF expression increases in prefrontal areas after learning an odor discrimination task (Naimark et al, 2007), and in motor areas after motor training (Klintsova et al, 2004). Finally, in vivo exogenous application of BDNF is sufficient to induce a longterm increase in synaptic strength that parallels many features of late-phase LTP (Messaoudi et al, 1998(Messaoudi et al, , 2002(Messaoudi et al, , 2007Ying et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

A Causal Role for Brain-Derived Neurotrophic Factor in the Homeostatic Regulation of Sleep

Faraguna¹,

Vyazovskiy²,

Nelson³

et al. 2008

J. Neurosci.

245

186

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Slow-wave activity (SWA), the EEG power between 0.5 and 4 Hz during non-rapid eye movement (NREM) sleep, is one of the best characterized markers of sleep need, because it increases as a function of preceding waking duration and decreases during sleep, but the underlying mechanisms remain unknown. We hypothesized that SWA is high at sleep onset because it reflects the occurrence, during the previous waking period, of widespread synaptic potentiation in cortical and subcortical areas. Consistent with this hypothesis, we recently showed that the more rats explore, the stronger is the cortical expression of BDNF during wakefulness, and the larger is the increase in SWA during the subsequent sleep period. There is compelling evidence that BDNF plays a causal role in synaptic potentiation, and exogenous application of BDNF in vivo is sufficient to induce long-term increases in synaptic strength. We therefore performed cortical unilateral microinjections of BDNF in awake rats and measured SWA during the subsequent sleep period. SWA during NREM sleep was higher in the injected hemisphere relative to the contralateral one. The effect was reversible within 2 h, and did not occur during wakefulness or rapid eye movement sleep. Asymmetries in NREM SWA did not occur after vehicle injections. Furthermore, microinjections, during wakefulness, of a polyclonal anti-BDNF antibody or K252a, an inhibitor of BDNF TrkB receptors, led to a local SWA decrease during the following sleep period. These effects were also reversible and specific for NREM sleep. These results show a causal link between BDNF expression during wakefulness and subsequent sleep regulation.

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Section: Discussionmentioning

confidence: 99%

A Causal Role for Brain-Derived Neurotrophic Factor in the Homeostatic Regulation of Sleep

Faraguna¹,

Vyazovskiy²,

Nelson³

et al. 2008

J. Neurosci.

245

186

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“…Motor learning and plasticity have been associated with TrkB and/or BDNF expression in the cortex (34, 35) and cerebellum (34), and BDNF has…”

Section: Lm22a-4 Activates Trkb Akt and Erk In Vivomentioning

confidence: 99%

Small molecule BDNF mimetics activate TrkB signaling and prevent neuronal degeneration in rodents

Massa¹,

Yang²,

Xie³

et al. 2010

J. Clin. Invest.

365

311

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Brain-derived neurotrophic factor (BDNF) activates the receptor tropomyosin-related kinase B (TrkB) with high potency and specificity, promoting neuronal survival, differentiation, and synaptic function. Correlations between altered BDNF expression and/or function and mechanism(s) underlying numerous neurodegenerative conditions, including Alzheimer disease and traumatic brain injury, suggest that TrkB agonists might have therapeutic potential. Using in silico screening with a BDNF loop-domain pharmacophore, followed by low-throughput in vitro screening in mouse fetal hippocampal neurons, we have efficiently identified small molecules with nanomolar neurotrophic activity specific to TrkB versus other Trk family members. Neurotrophic activity was dependent on TrkB and its downstream targets, although compound-induced signaling activation kinetics differed from those triggered by BDNF. A selected prototype compound demonstrated binding specificity to the extracellular domain of TrkB. In in vitro models of neurodegenerative disease, it prevented neuronal degeneration with efficacy equal to that of BDNF, and when administered in vivo, it caused hippocampal and striatal TrkB activation in mice and improved motor learning after traumatic brain injury in rats. These studies demonstrate the utility of loop modeling in drug discovery and reveal what we believe to be the first reported small molecules derived from a targeted BDNF domain that specifically activate TrkB.We propose that these compounds constitute a novel group of tools for the study of TrkB signaling and may provide leads for developing new therapeutic agents for neurodegenerative diseases.

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“…In the adult, BDNF expression is increased both by EE and physical exercise (Carro et al, 2000;Cotman and Berchtold, 2002;Adlard and Cotman, 2004;Klintsova et al, 2004), and this increase is mediated by IGF-1 (Carro et al, 2000). IGF-1 affects the BDNF system to mediate the effects of physical exercise on cognitive processes and synaptic plasticity (Ding et al, 2006).…”

Section: Igf-1 and Bdnfmentioning

confidence: 99%

Setting the Pace for Retinal Development: Environmental Enrichment Acts Through Insulin-Like Growth Factor 1 and Brain-Derived Neurotrophic Factor

Landi

Ciucci²,

Maffei³

et al. 2009

J. Neurosci.

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Environmental enrichment strongly affects visual system maturation both at retinal and cortical levels. Which molecular pathways are activated by an enriched environment (EE) to regulate visual system development has not been clarified. Here, we show that early [postnatal day 1 (P1) to P7] insulin-like growth factor 1 (IGF-1) injections in the eyes of non-EE rat pups mimic EE effects both in increasing BDNF levels in the retinal ganglion cell layer at P10 and in determining a more adult-like retinal acuity, assessed with pattern electroretinogram at P25. Blocking IGF-1 action in EE animals during the same early postnatal time window by injecting the IGF-1 receptor antagonist JB1 prevents EE effects both on BDNF expression and on retinal acuity maturation. Reducing BDNF expression in the retina of IGF-1-treated rats prevents IGF-1 effects on retinal acuity development. Finally, we show that tyrosine hydroxylase (TH) expression is increased in the retina of P10 EE and IGF-1-treated rats and that blocking TH expression in EE animals prevents EE from affecting retinal acuity development. Thus, early levels of IGF-1 play a key role in mediating EE effects on retinal development through an action that requires BDNF and involves dopaminergic amacrine cell network.

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Altered expression of BDNF and its high-affinity receptor TrkB in response to complex motor learning and moderate exercise

Cited by 158 publications

References 84 publications

A Causal Role for Brain-Derived Neurotrophic Factor in the Homeostatic Regulation of Sleep

A Causal Role for Brain-Derived Neurotrophic Factor in the Homeostatic Regulation of Sleep

Small molecule BDNF mimetics activate TrkB signaling and prevent neuronal degeneration in rodents

Setting the Pace for Retinal Development: Environmental Enrichment Acts Through Insulin-Like Growth Factor 1 and Brain-Derived Neurotrophic Factor

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