Locomotor exercise alters expression of pro‐brain‐derived neurotrophic factor, brain‐derived neurotrophic factor and its receptor TrkB in the spinal cord of adult rats

Macias, Matylda; Dwornik, A; Ziemlińska, Ewelina; Fehr, Susanna; Schachner, Melitta; Czarkowska-Bauch, Julita; Skup, M

doi:10.1111/j.1460-9568.2007.05498.x

Cited by 56 publications

(56 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Exercise increases BDNF in the brain (Berchtold, et al, 2005) and spinal cord (Gomez-Pinilla, et al, 2002, Zaheer, et al, 2006. Exercise also up regulates the BDNF receptor trkB (Macias, et al, 2007). Therefore, it is tempting to speculate that neurotrophins are involved in the enhanced axon elongation associated with exercise.…”

Section: Discussionmentioning

confidence: 99%

Treadmill training promotes axon regeneration in injured peripheral nerves

Sabatier

Redmon

Schwartz

et al. 2008

Experimental Neurology

150

153

View full text Add to dashboard Cite

Physical activity after spinal cord injury promotes improvements in motor function, but its effects following peripheral nerve injury are less clear. Although axons in peripheral nerves are known to regenerate better than those in the CNS, methods of accelerating regeneration are needed due to the slow overall rate of growth. Therefore we studied the effect of two weeks of treadmill locomotion on the growth of regenerating axons in peripheral nerves following injury. The common fibular nerves of thy-1-YFP-H mice, in which a subset of axons in peripheral nerves express yellow fluorescent protein (YFP), were cut and repaired with allografts from non-fluorescent littermates, and then harvested two weeks later. Mice were divided into groups of low-intensity continuous training (CT, 60 minutes), low-intensity interval training (IT; one group, 10 reps, 20 minutes total), and high-intensity IT (three groups, 2, 4, and 10 reps). One repetition consisted of two minutes of running and five minutes of rest. Sixty minutes of CT resulted in the highest exercise volume, whereas two reps of IT resulted in the lowest volume of exercise. The lengths of regenerating YFP + axons were measured in images of longitudinal optical sections of nerves. Axon profiles were significantly longer than control in all exercise groups except the low-intensity IT group. In the CT group and the high-intensity IT groups that trained with four or 10 repetitions axons were more than twice as long as unexercised controls. The number of intervals did not impact axon elongation. Axon sprouting was enhanced in IT groups but not the CT group. Thus exercise, even in very small quantities, increases axon elongation in injured peripheral nerves whereas continuous exercise resulting in higher volume (total steps) may have no net impact on axon sprouting.

show abstract

Section: Discussionmentioning

confidence: 99%

Treadmill training promotes axon regeneration in injured peripheral nerves

Sabatier

Redmon

Schwartz

et al. 2008

Experimental Neurology

150

153

View full text Add to dashboard Cite

show abstract

“…However, retrograde transport of NT-4 from the target could not be demonstrated in these preganglionic neurons, and thus the exact mechanisms involved in the NT-4-mediated survival of the lower intermediolateral cell column are not known. Preganglionic neurons located in the IML of the upper thoracic cord may be regulated by brain-derived neurotrophic factor (BDNF) , though these phenomena have not been well documented.In addition to preganglionic neurons, trkB-ir glial cells have been reported in the motor areas of the lumbar spinal cord [19] and were shown to be altered by exercise [13]. The extent to which the trkB-ir glial cells were present in the upper thoracic cord has not been described.…”

mentioning

confidence: 97%

“…Whether the anatomical relationship observed in the current study represents a similar interaction or a previously undescribed relationship is unknown at present. Though Macias et al [13] showed numerous trkB-ir glial cells surrounding large ventral horn motoneurons in the lumbar spinal cord, a potential interaction between these two cell types was not discussed. In the current study, no obvious differences in the number of these cells were observed following NGF administration.…”

mentioning

confidence: 99%

Characterization of trkB immunoreactive cells in the intermediolateral cell column of the rat spinal cord

McCartney

Abejuela

Isaacson

2008

Neuroscience Letters

View full text Add to dashboard Cite

The objective of the present study was to characterize the trkB receptor immunoreactive (-ir) cells in the intermediolateral cell column (IML) of the upper thoracic spinal cord. Small trkB-ir cells (area =56.1 +/− 4.4 µm 2 ) observed in the IML showed characteristics of oligodendrocytes and were frequently observed in close apposition to choline acetyltransferase (ChAT)-ir cell bodies. Large trkB-ir cells (area =209.3 +/− 25.2 µm 2 ) showed immunoreactivity for the neuronal marker NeuN, indicating their neuronal phenotype, as well as for ChAT, a marker for preganglionic neurons. TrkB and ChAT were co-localized in IML neurons primarily in cases that had received in vivo administration of nerve growth factor (NGF). These findings reveal two different cell types, oligodendrocytes and neurons, in the IML of the spinal cord that show trkB immunoreactivity, suggesting their regulation by BDNF and/or NT-4. In addition, there is evidence that NGF may play a role in the regulation of trkB-ir preganglionic neurons in the IML. Keywords preganglionic neurons; BDNF; NT-4; oligodendrocytes; sympatheticThe regulation of neurons and glial cells in the spinal cord is poorly characterized. TrkB expressing cells have been reported in the spinal cord, suggesting that they are regulated by either brain derived neurotrophic factor (BDNF) and/or neurotrophin -4 (NT-4). For example, in the lower intermediolateral cell column (IML; T7-T10), pre-ganglionic neurons have been shown to express trkB mRNA, are trkB immunoreactive (-ir) [17], and appear to be dependent on neurotrophin-4 (NT-4) derived from adrenal medullary chromaffin cells for survival [16]. However, retrograde transport of NT-4 from the target could not be demonstrated in these preganglionic neurons, and thus the exact mechanisms involved in the NT-4-mediated survival of the lower intermediolateral cell column are not known. Preganglionic neurons located in the IML of the upper thoracic cord may be regulated by brain-derived neurotrophic factor (BDNF) , though these phenomena have not been well documented.In addition to preganglionic neurons, trkB-ir glial cells have been reported in the motor areas of the lumbar spinal cord [19] and were shown to be altered by exercise [13]. The extent to which the trkB-ir glial cells were present in the upper thoracic cord has not been described.*Corresponding author, Lori G. Isaacson, Center for Neuroscience and Behavior, Department of Zoology, Miami University, 280 Pearson Hall, Oxford, OH 45056, Fax: 513-529-6900, isaacslg@muohio.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. The go...

show abstract

“…Whole hippocampal homogenates were separated by 15% PAGE and processed for Western blot analysis using rabbit anti-BDNF (1:1,000; SC546; Santa Cruz) followed by ECL Plus (Amersham) and quantified (11). The BDNF antisera detects distinct pro BDNF and mBDNF bands as described (11,35,36). Recombinant human BDNF (Chemicon) was added as positive control.…”

Section: (Si Text)mentioning

confidence: 99%

Up-regulating BDNF with an ampakine rescues synaptic plasticity and memory in Huntington's disease knockin mice

Simmons¹,

Rex

Palmer

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

236

192

View full text Add to dashboard Cite

Cognitive problems occur in asymptomatic gene carriers of Huntington's disease (HD), and mouse models of the disease exhibit impaired learning and substantial deficits in the cytoskeletal changes that stabilize long-term potentiation (LTP). The latter effects may be related to the decreased production of brainderived neurotrophic factor (BDNF) associated with the HD mutation. This study asked whether up-regulating endogenous BDNF levels with an ampakine, a positive modulator of AMPA-type glutamate receptors, rescues plasticity and reduces learning problems in HD (CAG140) mice. Twice-daily injections of a short half-life ampakine normalized BDNF levels, activity-driven actin polymerization in dendritic spines, and LTP stabilization in 8-week-old mutants. Comparable results were obtained in 16-week-old HD mice with more severe LTP deficits. Ampakine treatments had no measurable effect on the decreased locomotor activity observed in the mutants but offset their impairments in long-term memory. Given that ampakines are well tolerated in clinical trials and were effective in this study after brief exposures, these results suggest a novel strategy for chronic treatment of the cognitive difficulties that occur in the early stages of HD.actin polymerization ͉ CAG140 ͉ long-term potentiation ͉ theta burst stimulation ͉ unsupervised learning H untington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by a mutation involving the trinucleotide CAG in the huntingtin gene (1, 2). Although severe motor impairments characterize the disease, cognitive and memory deficits are also present and often appear in advance of other symptoms (3-6). Impaired learning that occurs before or concurrent with motor dysfunction or neuron loss has been described for HD mouse models (7-9) as have deficits in hippocampal long-term potentiation (LTP) (10-13), a form of synaptic plasticity widely regarded as a neurobiological substrate for memory. Understanding why LTP is severely impaired in HD mice could explain the cognitive dysfunction seen in patients with the disease.Our recent investigations into HD-associated plasticity deficits established that actin polymerization in dendritic spines, which normally stabilizes LTP (14, 15), is defective in HD knockin mice and most likely explains the rapid decay of potentiation (11). Pertinent to this finding, both HD mice and patients have reduced forebrain levels of brain-derived neurotrophic factor (BDNF) and its TrkB receptor (16,17). BDNF is a releasable neurotrophin that promotes activity-driven actin polymerization in dendritic spines (15, 18) and potently facilitates LTP induction by theta burst stimulation (TBS; refs. 19 and 20). Thus, an HD-related failure in BDNF signaling could remove an essential element of the system that modifies the spine cytoskeleton, thereby disrupting the stable synaptic changes needed to encode memory. Accordingly, applying low concentrations of BDNF fully restored TBS-induced actin polymerization and LTP in hippocampal slices prepared from HD ...

show abstract

Locomotor exercise alters expression of pro‐brain‐derived neurotrophic factor, brain‐derived neurotrophic factor and its receptor TrkB in the spinal cord of adult rats

Cited by 56 publications

References 73 publications

Treadmill training promotes axon regeneration in injured peripheral nerves

Treadmill training promotes axon regeneration in injured peripheral nerves

Characterization of trkB immunoreactive cells in the intermediolateral cell column of the rat spinal cord

Up-regulating BDNF with an ampakine rescues synaptic plasticity and memory in Huntington's disease knockin mice

Contact Info

Product

Resources

About