Expression of brain-derived neurotrophic factor protein in the adult rat central nervous system

Qiao, Yan; Rosenfeld, Robert; Matheson, Christine R.; Hawkins, Nessa; Lopez, Oscar T.; Bennett, L. G.; Welcher, Andy

doi:10.1016/s0306-4522(96)00613-6

Cited by 478 publications

(329 citation statements)

References 69 publications

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“…injection, although we did not detect significant increases in BDNF in other areas (not shown). It has been suggested that the diffusion of exogenously administered BDNF is restricted, due in part to the large number of TrkB receptors that bind and rapidly internalise BDNF [49]. This could account for the difference in BDNF detected in the dentate gyrus compared to the amount infused.…”

Section: Discussionmentioning

confidence: 99%

BDNF-stimulated intracellular signalling mechanisms underlie exercise-induced improvement in spatial memory in the male Wistar rat

Bechara

Lyne

Kelly

2014

Behavioural Brain Research

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• Exercised rats successfully completed challenging spatial task.• Exercised rats showed increase in KCl-stimulated BDNF release from dentate gyrus.• Exercised rats displayed increases in BDNF expression and cell division in dentate gyrus.• Exercised rats displayed activation of BDNF-stimulated signalling cascade.• BDNF injections mimicked effects of exercise on both memory and signalling events. a r t i c l e i n f o b s t r a c tExercise-induced improvements in learning are associated with neurotrophic and neurogenic changes in the dentate gyrus, but the intracellular signalling mechanisms that may mediate these improvements remain unknown. In the current study we investigate the effects of one week of forced exercise on spatial memory and analyse in parallel BDNF-stimulated signalling pathways in cells of the dentate gyrus. Additionally, we test whether a single intracerebroventricular (i.c.v.) injection of BDNF can mimic the observed cognitive and signalling changes. Male Wistar rats were assigned to exercised and sedentary groups and tested in a spatial task post-exercise. Tissue from the dentate gyrus was assessed for expression and release of BDNF, and for changes in expression and activation of TrkB, ERK and synapsin-1. In a separate set of experiments, male Wistar rats received a single i.c.v. injection of BDNF and were then tested in the same spatial learning task. Exercised and BDNF-treated (but not control) rats could successfully complete an object displacement task that tests spatial learning. Exercised rats and BDNF-treated rats displayed increases BDNF expression and ERK1 activation, while exercised rats showed increases in cell division, stimulated BDNF release, TrkB activation, and synapsin-1 expression in the dentate gyrus. We conclude that exercise-induced increases in BDNF in the dentate gyrus are sufficient to cause improvements in spatial memory by activating signalling cascades that enhance synaptic transmission in the hippocampus.

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Section: Discussionmentioning

confidence: 99%

BDNF-stimulated intracellular signalling mechanisms underlie exercise-induced improvement in spatial memory in the male Wistar rat

Bechara

Lyne

Kelly

2014

Behavioural Brain Research

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“…These results may have implications for our understanding of how endogenous BDNF may function, because the mossy fibers of the normal rat contain one of the highest concentrations of BDNF in the brain (Conner et al, 1997;Yan et al, 1997). However, it has not been shown previously that BDNF is expressed in sprouted mossy fibers of pilocarpine-treated rats.…”

Section: Bdnf Immunocytochemistrymentioning

confidence: 95%

“…Furthermore, regional specificity was apparent, because granule cell responses to perforant path stimulation were relatively unaffected by bath-applied BDNF. This apparent specificity was interesting in light of the fact that the mossy fibers are strongly immunoreactive to BDNF antisera relative to other afferents (Conner et al, 1997;Yan et al, 1997). Indeed, of all the fiber systems in the forebrain, BDNF expression is perhaps greatest in the mossy fibers (Conner et al, 1997;Yan et al, 1997).…”

Section: Abstract: Neurotrophin; Growth Factor; Hippocampus; Epilepsmentioning

confidence: 99%

Actions of Brain-Derived Neurotrophic Factor in Slices from Rats with Spontaneous Seizures and Mossy Fiber Sprouting in the Dentate Gyrus

1999

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This study examined the acute actions of brain-derived neurotrophic factor (BDNF) in the rat dentate gyrus after seizures, because previous studies have shown that BDNF has acute effects on dentate granule cell synaptic transmission, and other studies have demonstrated that BDNF expression increases in granule cells after seizures.Pilocarpine-treated rats were studied because they not only have seizures and increased BDNF expression in granule cells, but they also have reorganization of granule cell "mossy fiber" axons. This reorganization, referred to as "sprouting," involves collaterals that grow into novel areas, i.e., the inner molecular layer, where granule cell and interneuron dendrites are located. Thus, this animal model allowed us to address the effects of BDNF in the dentate gyrus after seizures, as well as the actions of BDNF on mossy fiber transmission after reorganization.In slices with sprouting, BDNF bath application enhanced responses recorded in the inner molecular layer to mossy fiber stimulation. Spontaneous bursts of granule cells occurred, and these were apparently generated at the site of the sprouted axon plexus. These effects were not accompanied by major changes in perforant path-evoked responses or paired-pulse inhibition, occurred only after prolonged (30-60 min) exposure to BDNF, and were blocked by K252a.The results suggest a preferential action of BDNF at mossy fiber synapses, even after substantial changes in the dentate gyrus network. Moreover, the results suggest that activation of trkB receptors could contribute to the hyperexcitability observed in animals with sprouting. Because human granule cells also express increased BDNF mRNA after seizures, and sprouting can occur in temporal lobe epileptics, the results may have implications for understanding temporal lobe epilepsy.Key words: neurotrophin; growth factor; hippocampus; epilepsy; glutamate; tyrosine kinase BDNF is widely recognized as a neurotrophin with an important role in normal development that has both trophic and protective effects (Hofer and Barde, 1988;Alderson et al., 1990;Knüsel et al., 1991;Spina et al., 1992;Yan et al., 1992;Lindholm et al., 1993;Morse et al., 1993;Beck et al., 1994;Cheng and Mattson et al., 1994;Ghosh et al., 1994;Kokaia et al., 1994;Acheson et al., 1995;McAllister et al., 1995;L owenstein and Arsenault, 1996). More recently it has become clear that BDN F also has acute, neuromodulatory effects on synaptic transmission. L ohof et al. (1993) first demonstrated that exposure of neuromuscular cultures to BDNF led to increased EPSC s, and this was followed by reports of related effects in other systems (Le␤man et al

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“…The localization within synaptic compartments, combined with recent evidence of anterograde transport, supports the hypothesis that BDNF may act directly at synapses to modulate synaptic transmission and plasticity. BDNF mRNA has been found in the granule layer of the dentate gyrus, and BDNF immunoreactivity in mossy fibers indicates anterograde transport of BDNF protein from dentate granule neurons (Conner et al 1997;Yan et al 1997). Perhaps the strongest evidence of anterograde transport of BDNF was provided by nuclear injections of BDNF-GFP cDNA, followed by subsequent visualization of the BDNF-GFP fusion protein in individual living neurons.…”

Section: Bdnf and Memory Consolidationmentioning

confidence: 99%

From Acquisition to Consolidation: On the Role of Brain-Derived Neurotrophic Factor Signaling in Hippocampal-Dependent Learning

Tyler¹,

Alonso²,

Bramham³

et al. 2002

Learn. Mem.

624

398

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One of the most rigorously investigated problems in modern neuroscience is to decipher the mechanisms by which experience-induced changes in the central nervous system are translated into behavioral acquisition, consolidation, retention, and subsequent recall of information. Brain-derived neurotrophic factor (BDNF) has recently emerged as one of the most potent molecular mediators of not only central synaptic plasticity, but also behavioral interactions between an organism and its environment. Recent experimental evidence indicates that BDNF modulates synaptic transmission and plasticity by acting across different spatial and temporal domains. BDNF signaling evokes both short-and long-term periods of enhanced synaptic physiology in both pre-and postsynaptic compartments of central synapses. Specifically, BDNF/TrkB signaling converges on the MAP kinase pathway to enhance excitatory synaptic transmission in vivo, as well as hippocampal-dependent learning in behaving animals. Emerging concepts of the intracellular signaling cascades involved in synaptic plasticity induced through environmental interactions resulting in behavioral learning further support the contention that BDNF/TrkB signaling plays a fundamental role in mediating enduring changes in central synaptic structure and function. Here we review recent literature showing the involvement of BDNF/TrkB signaling in hippocampal-dependent learning paradigms, as well as in the types of cellular plasticity proposed to underlie learning and memory.

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Expression of brain-derived neurotrophic factor protein in the adult rat central nervous system

Cited by 478 publications

References 69 publications

BDNF-stimulated intracellular signalling mechanisms underlie exercise-induced improvement in spatial memory in the male Wistar rat

BDNF-stimulated intracellular signalling mechanisms underlie exercise-induced improvement in spatial memory in the male Wistar rat

Actions of Brain-Derived Neurotrophic Factor in Slices from Rats with Spontaneous Seizures and Mossy Fiber Sprouting in the Dentate Gyrus

From Acquisition to Consolidation: On the Role of Brain-Derived Neurotrophic Factor Signaling in Hippocampal-Dependent Learning

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