Role of Trophic Factors on Activity-dependent Plasticity
We are interested on the mechanisms by which environmental factors affect neuronal health. We have found that trophic factors endogenous to the brain and spinal cord can be induced by the practice of select behaviors. We have recently reported that physical activity, learning, and nutritional factors control neurotrophins in the brain. These findings opened the exciting possibility that regulation of trophic factors by behavior can be a pivotal mechanism by which specific experiences can impact the structure and function of the CNS. It may account for the improvement of CNS function after trauma provided by rehabilitative therapies. On the contrary, it may explain the decay in function in aging or degenerative diseases following a lack of stimulation. These two avenues provide direction for my research program:
1) How trophic factors induced by activity can help functional recovery following brain and spinal cord trauma. We are using several exercise models to boost the production of trophic factors in the brain and spinal cord. Our goal is to provide critical information to guide the design of behavioral therapies for the reduction of the severity of insult or disease, and to increase CNS function.
2) We are evaluating the effects of lifestyle on trophic factor production, with resulting effects on circuit remodeling, synaptic function, and cognition. We believe that changes in trophic factor as a result of select experiences can affect neuronal health with profound consequences for cognitive function.
Molteni R, Zheng JQ, Ying Z, Gomez-Pinilla F, Twiss JL.
(2004).
Voluntary exercise increases axonal regeneration from sensory neurons Proc Natl Acad Sci U S A
101(22):
:8473-8
Hutchinson KJ, Gomez-Pinilla F, Crowe MJ, Ying Z, Basso DM.
(2004).
Three exercise paradigms differentially improve sensory recovery after spinal cord contusion in rats Brain
127(Pt 6)::
1403-14
Griesbach GS, Hovda DA, Molteni R, Wu A, Gomez-Pinilla F.
(2004).
Voluntary exercise following traumatic brain injury: brain-derived neurotrophic factor upregulation and recovery of function Neuroscience
125(1):
129-39
Vaynman S, Ying Z, Gomez-Pinilla F.
(2004).
Exercise induces BDNF and synapsin I to specific hippocampal subfields J Neurosci Res
76(3)::
356-62
Wu A, Ying Z, Gomez-Pinilla F.
(2004).
The interplay between oxidative stress and brain-derived neurotrophic factor modulates the outcome of a saturated fat diet on synaptic plasticity and cognition Eur J Neurosci
19(7)::
1699-707
Molteni R, Wu A, Vaynman S, Ying Z, Barnard RJ, Gomez-Pinilla F.
(2004).
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 Neuroscience
123(2):
429-40
Vaynman S, Ying Z, Gomez-Pinilla F.
(2003).
Interplay between brain-derived neurotrophic factor and signal transduction modulators in the regulation of the effects of exercise on synaptic-plasticity Neuroscience
122(3):
647-57
Ying Z, Roy RR, Edgerton VR, Gomez-Pinilla F.
(2003).
Voluntary exercise increases neurotrophin-3 and its receptor TrkC in the spinal cord Brain Res
987(1):
93-9
Li, H.H., Neufeld, E.F., Cai, Y., Zhao, H-Z., and Gómez-Pinilla, F
(2002).
Attenuated plasticity in neurons and astrocytes in the mouse model of Sanfilippo Syndrome Type B J. Neurosci. Res
69(1):
30-38
Molteni, R., Barnard, J.R., Ying, Z., Roberts, C.K., and Gómez-Pinilla, F.
(2002).
A high-fat, refined-sugar diet reduces BDNF, neuronal plasticity, and cognitive function Neuroscience
112(4):
803-814
Griesbach, G.S., Hovda, D.A., Molteni, R., and Gómez-Pinilla, F.
(2002).
Regulation of brain-derived neurotrophic factor after traumatic brain injury in the developing rat J. Neurotrauma
19 (7):
803-814
Molteni, Ying, Z., and Gómez-Pinilla, F.
(2002).
Differential expression of plasticity-related genes in the rat hippocampus after voluntary wheel running Eur. J. Neurosci
16 (6):
1107-1124
Gomez-Pinilla F, Ying Z, Roy RR, Molteni R, Edgerton VR.
(2002).
Voluntary exercise induces a BDNF-mediated mechanism that promotes neuroplasticity J Neurophysiol
88(5):
2187-95
Gómez-Pinilla, F., Ying, J. P. Opazo L., Roy, R., and Edgerton, R.,
(2001).
Exercise up-regulates BDNF mRNA and protein in the spinal cord and skeletal muscle Eur. J. Neurosci
13:
1078-1084
Gómez-Pinilla, F., So, V., and Kesslak, J.P
(2001).
Spatial Learning induces trkB and Synapsin I mRNAs in the hippocampus Brain Res
904:
13-19
Gómez-Pinilla, F., Choi, J., and Ryba, E.A.
(2000).
The GABA agonist diazepam induces FGF-2 in the hippocampus and striatum Brain Res. Bull
53(3):
283-289
Gómez-Pinilla, F. and Dao, L.,
(1999).
Diazepam induces FGF-2 and its mRNA in the spinal cord NeuroReport
10(6):
1273-1276
Kesslak, JP., So., V., Choi, J., Cotman, C.W., and Gómez-Pinilla, F
(1998).
Learning upergulates BDNF mRNA: A Mechanism to facilitate encoding and circuit maintenance, Behav. Neurosci
112:
1012-1019
Gómez-Pinilla, F., Choi, J., and Ryba, E.A.
(1998).
Visual input regulates the expression of FGF and its receptor. Neural substrates for the effects of the environment on brain plasticity Neuroscience,
88:
-
Gómez-Pinilla, F., So, V., and Kesslak, J-P
(1998).
Spatial learning and physical activity contribute to the induction of FGF: Neural substrates for increased cognition associated with exercise Neuroscience
85(1):
53-61
Gómez-Pinilla, F., Dao, L., and So., V,
(1997).
Physical activity induces fibroblast growth factor in the hippocampus, Brain Res
764 (1-2):
1-8
Gómez-Pinilla, F., Miller, S., Choi, J. and Cotman, C.W.,
(1997).
Heparan sulfate potentiates the autocrine action of FGF-2 in astrocytes: An in vivo and in vivo study, Neuroscience
76(1):
137-145
Neeper, S.A., Gómez-Pinilla, F., Choi, J. and Cotman, C.W
(1996).
., Physical activity increases the mRNA for brain-derived neurotrophic factor and nerve growth factor in rat brain, Brain Res
726:
49-56
Gómez-Pinilla, F., Van der Wal, E.A. and Cotman, C.W.,
(1995).
Possible coordinated gene expressions for FGF receptor, FGF-5 and FGF-2 following seizures Exp. Neurol
133:
164-174
Neeper, S.A., Gómez-Pinilla, F., Choi, J. and Cotman, C.W
(1995).
Exercise and brain neurotrophins Nature
373:
-