Fernando Gómez-Pinilla, Ph.D.

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UCLA Division of Neurosurgery & Dept. of Physiological Science 


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Recent Publications

Nature Reviews Neuroscience: 
Brain foods: the effects of nutrients on brain function

Nat Rev Neurosci
. 2008, 9(7):568-578. [Abstract] [Full Text]

Figure 1 | Effects of feeding on cognition. Neural circuits that are involved in feeding behaviour show precise coordination with brain centres that modulate energy homeostasis and cognitive function. The effects of food on cognition and emotions can start before the act of feeding itself, as the recollection of foods through olfactory and visual sensory inputs alters the emotional status of the brain. The ingestion of foods triggers the release of hormones or peptides, such as insulin and glucagon-like peptide 1 (GLP1)31, into the circulation (see REF. 31 for a review); these substances can then reach centres such as the hypothalamus and the hippocampus and activate signal-transduction pathways that promote synaptic activity and contribute to learning and memory. In turn, the lack of food that is signalled by an empty stomach can elicit the release of ghrelin, which can also support synaptic plasticity and cognitive function. Chemical messages derived from adipose tissue through leptin can activate specific receptors in the hippocampus and the hypothalamus, and influence learning and memory. The positive actions of leptin on hippocampus-dependent synaptic plasticity — that is, its actions on NMDA (N-methyl-d-aspartate) receptor function and long-term potentiation facilitation — are well characterized (see REF. 13 for a review). Insulin-like growth factor 1 (IGF1) is produced by the liver and by skeletal muscle in response to signals derived from metabolism and exercise. IGF1 can signal to neurons in the hypothalamus and the hippocampus, with resulting effects on learning and memory performance. In addition to regulating appetite, the hypothalamus coordinates activity in the gut and integrates visceral function with limbic-system structures such as the hippocampus, the amygdala and the cerebral cortex. Visceral signals can also modulate cognition and body physiology through the hypothalamic–pituitary axis (HPA). The effects of the hypothalamus can also involve the immune system, as it heavily innervates the thymus and several immune-system molecules can affect synaptic plasticity and cognition. The parasympathetic innervation of the gut by the vagus nerve provides sensory information to the brain, enabling gut activity to influence emotions. In turn, emotions can also influence the viscera through parasympathetic efferents in the vagus nerve. Vagal nerve stimulation is being used therapeutically to treat chronic depression.


Figure 2 | Energy homeostasis and cognition. Diet and exercise can affect mitochondrial energy production, which is important for maintaining neuronal excitability and synaptic function. The combination of certain diets and exercise can have additive effects on synaptic plasticity and cognitive function. ATP produced by mitochondria might activate brain-derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF1), which support synaptic plasticity and cognitive function. Energy balancing molecules, such as ubiquitous mitochondrial creatine kinase (uMtCK), AMP-activated protein kinase (AMPK) and uncoupling protein 2 (UCP2)141,146, interact with BDNF to modulate synaptic plasticity and cognition. Excess energy production caused by high caloric intake or strenuous exercise results in the formation of reactive oxygen species (ROS). When ROS levels exceed the buffering capacity of the cell, synaptic plasticity and cognitive function are compromised, probably owing to a reduction in the actions of signal-transduction modulators such as BDNF. Energy metabolism can also affect molecules such as silent information regulator 1 (SIRT1), a histone deacetylase that contributes to the reduction of ROS and promotes chromatin modifications that underlie epigenetic alterations that might affect cognition146. On the basis of its demonstrated susceptibility for epigenetic modification73, another potential target for the effects of diet on epigenetics is the BDNF gene. Two main findings support a mechanism whereby exercise, similar to diet, enhances cognitive processes through effects on energy metabolism and synaptic plasticity. First, the combination of exercise and certain diets elevates the expression of uMtCK, AMPK and UCP2, which might affect energy homeostasis and brain plasticity. Second, disruption of energy homeostasis during voluntary wheel-running abolished the effects of exercise on the actions of BDNF and BDNF end products that are important for learning and memory, suggesting that energy metabolism influences BDNF function147.


Figure 3 | Dietary omega-3 fatty acids can affect synaptic plasticity and cognition. The omega-3 fatty acid docosahexaenoic acid (DHA), which humans mostly attain from dietary fish, can affect synaptic function and cognitive abilities by providing plasma membrane fluidity at synaptic regions. DHA constitutes more than 30% of the total phospholipid composition of plasma membranes in the brain, and thus it is crucial for maintaining membrane integrity and, consequently, neuronal excitability and synaptic function. Dietary DHA is indispensable for maintaining membrane ionic permeability and the function of transmembrane receptors that support synaptic transmission and cognitive abilities. Omega-3 fatty acids also activate energy-generating metabolic pathways that subsequently affect molecules such as brain-derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF1). IGF1 can be produced in the liver and in skeletal muscle, as well as in the brain, and so it can convey peripheral messages to the brain in the context of diet and exercise. BDNF and IGF1 acting at presynaptic and postsynaptic receptors can activate signalling systems, such as the mitogen-activated protein kinase (MAPK) and calcium/calmodulin-dependent protein kinase II (CaMKII) systems, which facilitate synaptic transmission and support long-term potentiation that is associated with learning and memory. BDNF has also been shown to be involved in modulating synaptic plasticity and cognitive function through the phosphatidylinositol 3‑kinase (PI3K)/Akt/ mammalian target of rapamycin (mTOR) signalling pathway. The activities of the mTOR and Akt signalling pathways are also modulated by metabolic signals such as insulin and leptin (not shown). 4EBP, eukaryotic translation-initiation factor 4E binding protein; CREB, cyclic AMP-responsive element (CRE)-binding protein; IGFR, insulin-like growth factor receptor; IRS1, insulin receptor substrate 1; p70S6K, p70 S6 kinase.

 

Exercise

Gomez-Pinilla F.

The influences of diet and exercise on mental health through hormesis.

Ageing Res Rev. 2008, 7:49-62. [Abstract] [PDF]

 

Chytrova G, Ying Z, Gomez-Pinilla F.

Exercise normalizes levels of MAG and Nogo-A growth inhibitors after brain trauma.

Eur J Neurosci. 2008, 27:1-11. [Abstract] [PDF]

 

Vaynman S, Ying Z, Gomez-Pinilla F.

The select action of hippocampal calcium calmodulin protein kinase II in mediating exercise-enhanced cognitive function.

Neuroscience. 2007, 144:825-833. [Abstract] [PDF]

 

Ghiani CA, Ying Z, de Vellis J, Gomez-Pinilla F.

Exercise decreases myelin-associated glycoprotein expression in the spinal cord and positively modulates neuronal growth.

Glia. 2007, 55:966-975. [Abstract] [PDF]

 

Vaynman S, Gomez-Pinilla F.
Revenge of the "Sit": How lifestyle impacts neuronal and cognitive health through molecular systems that interface energy metabolism with neuronal plasticity.
J Neurosci Res. 2006, 84:699-715.
[Abstract] [PDF]

 

Ding Q, Vaynman S, Souda P, Whitelegge JP, Gomez-Pinilla F.

Exercise affects energy metabolism and neural plasticity-related proteins in the hippocampus as revealed by proteomic analysis.

Eur J Neurosci. 2006, 24:1265-1276. [Abstract] [PDF]

 

Ding Q, Vaynman S, Akhavan M, Ying Z, Gomez-Pinilla F.
Insulin-like growth factor I interfaces with brain-derived neurotrophic factor-mediated synaptic plasticity to modulate aspects of exercise-induced cognitive function.
Neuroscience.
2006, 140:823-833
[Abstract] [PDF]

 

Vaynman S, Ying Z, Wu A, Gomez-Pinilla F.
Coupling energy metabolism with a mechanism to support brain-derived neurotrophic factor-mediated synaptic plasticity.
Neuroscience, 2006,139:1221-
1234. [Abstract] [PDF]

 

Vaynman SS, Ying Z, Yin D, Gomez-Pinilla F.

Exercise differentially regulates synaptic proteins associated to the function of BDNF.

Brain Res. 2006, 1070:124-130. [Abstract] [PDF]

 

Vaynman S, Gomez-Pinilla F. 
License to run: exercise impacts functional plasticity in the intact and injured central nervous system by using neurotrophins.
Neurorehabil Neural Repair. 2005, 19:283-295. [Abstract] [PDF]

 

Ying Z, Roy RR, Edgerton VR, Gomez-Pinilla F.
Exercise restores levels of neurotrophins and synaptic plasticity following spinal cord injury.
Exp Neurol. 2005, 193:411-419 [Abstract] [PDF]

 

Molteni R, Zheng JQ, Ying Z, Gomez-Pinilla F, Twiss JL.
Voluntary exercise increases axonal regeneration from sensory neurons.
Proc Natl Acad Sci USA 2004, 101:8473-8478 [Abstract] [PDF]
 

Vaynman S, Ying Z, Gomez-Pinilla F.
Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition.
Eur J Neurosci. 2004, 20:2580-2590 [Abstract] [PDF]

>> More

 

 

Diet

Wu A, Ying Z, Gomez-Pinilla F.

Oxidative stress modulates Sir2alpha in rat hippocampus and cerebral cortex.

Eur J Neurosci. 2006, 23:2573-2580. [Abstract] [PDF]

 

Wu A, Ying Z, Gomez-Pinilla F. 
Dietary curcumin counteracts the outcome of traumatic brain
injury on oxidative stress, synaptic plasticity, and cognition.
Exp Neurol. 2006
, 197:309-317. [Abstract] [PDF]

 

Wu A, Ying Z, Gomez-Pinilla F.
Dietary omega-3 fatty acids normalize BDNF levels, reduce oxidative damage, and counteract learning disability after traumatic brain injury in rats.
J Neurotrauma. 2004, 21:1457-1467 [Abstract] [PDF]

 

Wu A, Ying Z, Gomez-Pinilla F.
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. 2004, 19:1699-1707 [Abstract] [PDF]

More Publications

Exercise

Ying Z, Roy RR, Edgerton VR, Gomez-Pinilla F.
Exercise restores levels of neurotrophins and synaptic plasticity following spinal cord injury.
Exp Neurol. 2005, 193:411-419 [Abstract] [PDF]

 

Molteni R, Zheng JQ, Ying Z, Gomez-Pinilla F, Twiss JL.
Voluntary exercise increases axonal regeneration from sensory neurons.
Proc Natl Acad Sci USA 2004, 101:8473-8478 [Abstract] [PDF]
 

Vaynman S, Ying Z, Gomez-Pinilla F.
Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition.
Eur J Neurosci. 2004, 20:2580-2590 [Abstract] [PDF]

 

Vaynman S, Ying Z, Gomez-Pinilla F.
Exercise induces BDNF and synapsin I to specific hippocampal subfields.
J Neurosci Res. 2004, 76:356-362 [Abstract] [PDF]

 

Molteni R, Wu A, Vaynman S, Ying Z, Barnard RJ, Gomez-Pinilla F.
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. 2004, 123:429-440. [Abstract] [PDF]

 

Vaynman S, Ying Z, Gomez-Pinilla F.
Interplay between brain-derived neurotrophic factor and signal transduction modulators in the regulation of the effects of exercise on synaptic-plasticity.
Neuroscience. 2003, 122:647-657 [Abstract] [PDF]

 

Ying Z, Roy RR, Edgerton VR, Gomez-Pinilla F.

Voluntary exercise increases neurotrophin-3 and its receptor TrkC in the spinal cord.
Brain Res. 2003, 987:93-99 [Abstract] [PDF]

 

Gomez-Pinilla F, Ying Z, Roy RR, Molteni R, Edgerton VR.
Voluntary exercise induces a BDNF-mediated mechanism that promotes neuroplasticity.
J Neurophysiol. 2002, 88:2187-2195  [Abstract] [PDF]

 

Molteni R, Ying Z, Gomez-Pinilla F.
Differential effects of acute and chronic exercise on plasticity-related genes in the rat hippocampus revealed by microarray.
Eur J Neurosci. 2002, 16:1107-1116 [Abstract] [PDF]

 

Gomez-Pinilla F, So V, Kesslak JP.

Spatial learning induces neurotrophin receptor and synapsin I in the hippocampus.
Brain Res. 2001, 904:13-19 [Abstract] [PDF]

 

Gomez-Pinilla F, Ying Z, Opazo P, Roy RR, Edgerton VR.

Differential regulation by exercise of BDNF and NT-3 in rat spinal cord and skeletal muscle.
Eur J Neurosci. 2001, 13:1078-1084 [Abstract] [PDF]

 

 

Diet

Wu A, Ying Z, Gomez-Pinilla F. 
Dietary curcumin counteracts the outcome of traumatic brain
injury on oxidative stress, synaptic plasticity, and cognition.
Exp Neurol. 2006, 197:309-317.
[Abstract] [PDF]

 

Wu A, Ying Z, Gomez-Pinilla F.
Dietary omega-3 fatty acids normalize BDNF levels, reduce oxidative damage, and counteract learning disability after traumatic brain injury in rats.
J Neurotrauma. 2004, 21:1457-1467 [Abstract] [PDF]

 

Wu A, Ying Z, Gomez-Pinilla F.
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. 2004, 19:1699-1707 [Abstract] [PDF]

 

Wu A, Molteni R, Ying Z, Gomez-Pinilla F.
A saturated-fat diet aggravates the outcome of traumatic brain injury on hippocampal plasticity and cognitive function by reducing brain-derived neurotrophic factor.
Neuroscience. 2003, 119:365-375 [Abstract] [PDF]

 

Molteni R, Barnard RJ, Ying Z, Roberts CK, Gomez-Pinilla F.
A high-fat, refined sugar diet reduces hippocampal brain-derived neurotrophic factor, neuronal plasticity, and learning.
Neuroscience. 2002, 112:803-814 [Abstract] [PDF]

 

Spinal Cord Injury

Gomez-Pinilla F, Ying Z, Roy RR, Hodgson J, Edgerton VR.
Afferent input modulates neurotrophins and synaptic plasticity in the spinal cord.
J Neurophysiol. 2004, 92:3423-3432 [Abstract] [PDF]

 

Hutchinson KJ, Gomez-Pinilla F, Crowe MJ, Ying Z, Basso DM.

Three exercise paradigms differentially improve sensory recovery after spinal cord contusion in rats.
Brain. 2004, 127:1403-1414 [Abstract] [PDF]

 

 

Reviews

Ang ET, Gomez-Pinilla F. 
Potential therapeutic effects of exercise to the brain.
Curr Med Chem. 2007, 14:2564-71. [Abstract] [PDF]

 

Vaynman S, Gomez-Pinilla F. 
License to run: exercise impacts functional plasticity in the intact and injured central nervous system by using neurotrophins.
Neurorehabil Neural Repair. 2005, 19:283-295. [Abstract] [PDF]

 

Gomez-Pinilla F, Vaynman S.
A "deficient environment" in prenatal life may compromise systems important for cognitive function by affecting BDNF in the hippocampus.
Exp Neurol. 2005, 192:235-243 [Abstract] [PDF]

 


Contact Information:

Fernando Gómez-Pinilla, Ph.D.
Professor,
Div. of Neurosurgery and Dept. of Physiological Science
University of California at Los Angeles

Life Science Building 1836
621 Charles E. Young Drive South
Los Angeles, CA 90095

Office: Phone/Fax:(310) 206-9693
Lab:
(310) 825-1788

E-mail: fgomezpi@ucla.edu