Exercise induces BDNF and synapsin I to specific hippocampal subfields

To assess the relationship between brain‐derived neurotrophic factor (BDNF) and synapsin I in the hippocampus during exercise, we employed a novel microsphere injection method to block the action of BDNF through its tyrosine kinase (Trk) receptor and subsequently measure the mRNA levels of synapsin I, using real‐time TaqMan RT‐PCR for RNA quantification. After establishing a causal link between BDNF and exercise‐induced synapsin I mRNA levels, we studied the exercise‐induced distribution of BDNF and synapsin I in the rodent hippocampus. Quantitative immunohistochemical analysis revealed increases of BDNF and synapsin I in CA3 stratum lucidum and dentate gyrus, and synapsin I alone in CA1 stratum radiatum and stratum laconosum moleculare. These results indicate that exercise induces plasticity of select hippocampal transsynaptic circuitry, possibly comprising a spatial restriction on synapsin I regulation by BDNF. © 2004 Wiley‐Liss, Inc.

[1]  C. Cotman,et al.  Density and distribution of NMDA receptors in the human hippocampus in Alzheimer's disease , 1986, Brain Research.

[2]  P. Schwartzkroin,et al.  Neurotrophin expression in rat hippocampal slices: A stimulus paradigm inducing LTP in CA1 evokes increases in BDNF and NT-3 mRNAs , 1992, Neuron.

[3]  J. Wehner,et al.  Physical activity enhances spatial learning performance with an associated alteration in hippocampal protein kinase C activity in C57BL/6 and DBA/2 mice , 1993, Brain Research.

[4]  F. Gomez-Pinilla,et al.  A saturated-fat diet aggravates the outcome of traumatic brain injury on hippocampal plasticity and cognitive function by reducing brain-derived neurotrophic factor , 2003, Neuroscience.

[5]  G Salvendy,et al.  Impact of Physical Fitness on Strategy Development in Decision-Making Tasks , 1986, Perceptual and motor skills.

[6]  J J Quattrochi,et al.  Mapping neuronal inputs to REM sleep induction sites with carbachol-fluorescent microspheres. , 1989, Science.

[7]  K. Sobue,et al.  Localization of synapsin I in normal fibers and regenerating axonal sprouts of the rat sciatic nerve , 1996, Histochemistry and Cell Biology.

[8]  F Benfenati,et al.  Synaptic vesicle phosphoproteins and regulation of synaptic function. , 1993, Science.

[9]  D. Hovda,et al.  Alterations in BDNF and synapsin I within the occipital cortex and hippocampus after mild traumatic brain injury in the developing rat: reflections of injury-induced neuroplasticity. , 2002, Journal of neurotrauma.

[10]  A study of the effectiveness of botulinum toxin type A (Dysport) in the management of muscle spasticity. , 1998, Disability and rehabilitation.

[11]  Lawrence C. Katz,et al.  NT-4-mediated rescue of lateral geniculate neurons from effects of monocular deprivation , 1995, Nature.

[12]  W. Dunlap,et al.  Effect of exercise on longevity, body weight, locomotor performance, and passive-avoidance memory of C57BL/6J mice , 1985, Neurobiology of Aging.

[13]  T J Sejnowski,et al.  Running enhances neurogenesis, learning, and long-term potentiation in mice. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[14]  C. Cotman,et al.  Physical activity increases mRNA for brain-derived neurotrophic factor and nerve growth factor in rat brain , 1996, Brain Research.

[15]  T Bonhoeffer,et al.  Hippocampal long-term potentiation is impaired in mice lacking brain-derived neurotrophic factor. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[16]  G. Golarai,et al.  Mossy fiber synaptic reorganization induced by kindling: time course of development, progression, and permanence , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[17]  S K Rushton,et al.  Improving cognitive function after brain injury: the use of exercise and virtual reality. , 1999, Archives of physical medicine and rehabilitation.

[18]  B. Lu,et al.  Regulation of synaptic responses to high-frequency stimulation and LTP by neurotrophins in the hippocampus , 1996, Nature.

[19]  Howard J. Federoff,et al.  Regulated Release and Polarized Localization of Brain-Derived Neurotrophic Factor in Hippocampal Neurons , 1996, Molecular and Cellular Neuroscience.

[20]  E. Schuman,et al.  Neurotrophins and Time: Different Roles for TrkB Signaling in Hippocampal Long-Term Potentiation , 1997, Neuron.

[21]  M. Mattson.  Neuroprotective signaling and the aging brain: take away my food and let me run 1 1 Published on the World Wide Web on 24 August 2000. , 2000, Brain Research.

[22]  Catherine R. Harrison,et al.  Ageing, fitness and neurocognitive function , 1999, Nature.

[23]  V. Edgerton,et al.  Differential regulation by exercise of BDNF and NT‐3 in rat spinal cord and skeletal muscle , 2001, The European journal of neuroscience.

[24]  L. C. Katz,et al.  Focal delivery of neurotrophins into the central nervous system using fluorescent latex microspheres. , 1997, BioTechniques.

[25]  P. Greengard,et al.  Synapsins as mediators of BDNF-enhanced neurotransmitter release , 2000, Nature Neuroscience.

[26]  Keiko Sato,et al.  Increased synapsin I immunoreactivity during long-term potentiation in rat hippocampus , 2000, Brain Research.

[27]  R. Melloni,et al.  Dynamics of synapsin I gene expression during the establishment and restoration of functional synapses in the rat hippocampus , 1994, Neuroscience.

[28]  Zhe Ying,et al.  Differential effects of acute and chronic exercise on plasticity‐related genes in the rat hippocampus revealed by microarray , 2002, The European journal of neuroscience.

[29]  H. Scharfman,et al.  Actions of Brain-Derived Neurotrophic Factor in Slices from Rats with Spontaneous Seizures and Mossy Fiber Sprouting in the Dentate Gyrus , 1999, The Journal of Neuroscience.

[30]  R. Racine,et al.  Long-term potentiation trains induce mossy fiber sprouting , 1997, Brain Research.

[31]  Y. Jo,et al.  The induction of BDNF and c-fos mRNA in the hippocampal formation after febrile seizures , 2001, Neuroreport.

[32]  K. Schlingensiepen,et al.  Changes in the expression of synapsin I and II messenger RNA during postnatal rat brain development , 1996, Experimental Brain Research.

[33]  H. Scharfman.  Hyperexcitability in combined entorhinal/hippocampal slices of adult rat after exposure to brain-derived neurotrophic factor. , 1997, Journal of neurophysiology.

[34]  R. Faull,et al.  Brain-derived neurotrophic factor is reduced in Alzheimer's disease. , 1997, Brain research. Molecular brain research.

[35]  J. Lindsay,et al.  Physical activity and risk of cognitive impairment and dementia in elderly persons. , 2001, Archives of neurology.

[36]  N. Hirokawa,et al.  Synapsin I deficiency results in the structural change in the presynaptic terminals in the murine nervous system , 1995, The Journal of cell biology.

[37]  E. Welker,et al.  Upregulation of BDNF mRNA Expression in the Barrel Cortex of Adult Mice after Sensory Stimulation , 1996, The Journal of Neuroscience.

[38]  C. Bramham,et al.  Acute intrahippocampal infusion of BDNF induces lasting potentiation of synaptic transmission in the rat dentate gyrus. , 1998, Journal of neurophysiology.

[39]  C. Cotman,et al.  Exercise and brain neurotrophins , 1995, Nature.

[40]  D. Fordyce,et al.  Enhancement of spatial learning in F344 rats by physical activity and related learning-associated alterations in hippocampal and cortical cholinergic functioning , 1991, Behavioural Brain Research.

[41]  B. Lom,et al.  Brain-Derived Neurotrophic Factor Differentially Regulates Retinal Ganglion Cell Dendritic and Axonal Arborization In Vivo , 1999, The Journal of Neuroscience.

[42]  Andrew Gloster,et al.  Synaptic Innervation Density Is Regulated by Neuron-Derived BDNF , 1997, Neuron.

[43]  A. Konnerth,et al.  Neurotrophin-evoked rapid excitation through TrkB receptors , 1999, Nature.

[44]  Keiko Sato,et al.  Time-dependent changes in rat hippocampal synapsin I mRNA expression during long-term potentiation , 1998, Brain Research.

[45]  R. Heumann,et al.  BDNF-GFP containing secretory granules are localized in the vicinity of synaptic junctions of cultured cortical neurons. , 1998, Journal of cell science.

[46]  Keiko Sato,et al.  Increment of synapsin I immunoreactivity in the hippocampus of the rat kindling model of epilepsy , 2000, Neuroreport.

[47]  B. Lu,et al.  Role of Neurotrophins in Synapse Development and Plasticity , 1997, Reviews in the neurosciences.

[48]  J. Kesslak,et al.  Spatial learning induces neurotrophin receptor and synapsin I in the hippocampus , 2001, Brain Research.

[49]  E. Kandel,et al.  A Macromolecular Synthesis-Dependent Late Phase of Long-Term Potentiation Requiring cAMP in the Medial Perforant Pathway of Rat Hippocampal Slices , 1996, The Journal of Neuroscience.

[50]  P. Greengard,et al.  Distinct Roles of Synapsin I and Synapsin II during Neuronal Development , 1998, Molecular medicine.

[51]  D. Amaral,et al.  The three-dimensional organization of the hippocampal formation: A review of anatomical data , 1989, Neuroscience.