Mark Mattson

Mark Mattson

Mark Mattson in 2009.
Born Mark P. Mattson
1957
Rochester, Minnesota
Nationality American
Fields
Institutions
Alma mater
Spouse
  • Joanne Mattson

Mark P. Mattson is Chief of the Laboratory of Neurosciences at the National Institute on Aging Intramural Research Program National Institute on Aging. He is also Professor of Neuroscience at Johns Hopkins University.

Early life and education

Mark P. Mattson was born in 1957 in Rochester, Minnesota. After receiving his PhD degree from the University of Iowa, Dr. Mattson completed a postdoctoral fellowship in Developmental Neuroscience at Colorado State University. He then joined the Sanders-Brown Center on Aging and the Department of Anatomy and Neurobiology at the University of Kentucky College of Medicine as an Assistant Professor. Dr. Mattson was promoted to the rank of Associate Professor with tenure and then to Full Professor. In 2000, Dr. Mattson took the position of Chief of the Laboratory of Neurosciences at the National Institute on Aging in Baltimore, where he leads a multi-faceted research team that applies cutting-edge technologies in research aimed at understanding molecular and cellular mechanisms of brain aging and the pathogenesis of neurodegenerative disorders. He is also a Professor in the Department of Neuroscience at Johns Hopkins University School of Medicine.

Career

Dr. Mattson is considered a leader in the area of cellular and molecular mechanisms underlying neuronal plasticity and neurodegenerative disorders, and has made major contributions to understanding the pathogenesis of Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and stroke, and to their prevention and treatment. He has published more than 700 peer-reviewed articles in leading journals and books, and has edited 10 books in the areas of neuronal signal transduction, neurodegenerative disorders and mechanisms of aging. Dr. Mattson has been the most highly cited neuroscientist in the world according to the ISI information database (http://www.in-cites.com/top/2006/second06-neu.html), and he has an h index of over 170 (i.e., he has authored more than 170 articles that have each been cited at least 170 times[1] Profiles of Dr. Mattson have been published in numerous forums including: Science Watch (http://archive.sciencewatch.com/ana/st/alz2/11julSTAlz2Matt/). Nature Medicine (http://www.nature.com/nm/journal/v10/n4/full/nm0404-324.html).

Awards and recognition

Dr. Mattson has received many awards including the Metropolitan Life Foundation Medical Research Award, the Alzheimer's Association Zenith Award, the Jordi Folch Pi Award, the Santiago Grisolia Chair Prize, the Tovi Comet-Walerstein Science Award, and several Grass Lectureship Awards. He was elected as a Fellow of the American Association for the Advancement of Science. He is Editor-in-Chief of NeuroMolecular Medicine and Ageing Research Reviews, and has been/is a Managing or Associate Editor of the Journal of Neuroscience, Trends in Neurosciences, the Journal of Neurochemistry, the Neurobiology of Aging, and the Journal of Neuroscience Research. Dr. Mattson has served on several NIH study sections and on scientific advisory boards for many research foundations. He has trained more than 70 postdoctoral and predoctoral scientists, and has made major contributions to the education of undergraduate, graduate and medical students.

Contributions to research

Research by Dr. Mattson in the area of molecular and cellular mechanisms that regulate neuronal plasticity and survival, in the contexts of brain development and aging, has established a new conceptual framework for understanding the pathogenesis of neurodegenerative disorders. He showed that perturbations of cellular signaling mechanisms that regulate developmental neuroplasticity are responsible for synaptic dysfunction and cell death in neurodegenerative disorders. In particular, he has been a leader in advancing an understanding of the molecular events that destabilize cellular calcium homeostasis and ultimately cause the death of neurons in Alzheimer's disease, Parkinson's disease, ALS and stroke.[2][3] Here are some specific examples of seminal findings of Dr. Mattson that represent major advances in the fields of neuroscience and neurodegenerative disorders.

In his early research Dr. Mattson discovered that the neurotransmitter glutamate, previously believed to function only at synapses, plays a key role in regulating dendrite outgrowth and synaptogenesis.[4][5] He then showed that neurotrophic factors can modify the effects of neurotransmitters on neurite outgrowth, synaptogenesis and cell survival.[6][7] Glutamate and neurotrophic factors exert their effects on neuronal plasticity and survival by modulating cellular calcium homeostasis. These findings revealed the molecular basis for activity-dependent regulation of neuronal plasticity. Importantly, Dr. Mattson’s discovery that neurotrophic factors such as bFGF, BDNF and IGFs can protect neurons against dysfunction and degeneration in experimental models of stroke and Alzheimer's disease led to clinical trials of neurotrophic factor delivery in patients with stroke and neurodegenerative disorders.

A major contribution to the fields of neuroscience and neurology were Dr. Mattson’s studies that elucidated mechanisms of synaptic dysfunction and degeneration in AD. He showed that amyloid beta-peptide (Abeta) induces membrane-associated oxidative stress which disrupts calcium homeostasis and renders neurons vulnerable to excitotoxicity and apoptosis.[8] His work showed that the lipid peroxidation product 4-hydroxynonenal mediates Abeta toxicity by covalently modifying ion-motive ATPases, and glucose and glutamate transporters.[9][10] He also showed that presenilin mutations endanger neurons by perturbing endoplasmic reticulum calcium regulation.[11] His work also revealed a physiological role for the secreted form of amyloid precursor protein generated by alpha-secretase activity (sAPPalpha). He showed that sAPPalpha suppresses neuronal excitability and protects neurons against excitotoxicity by a mechanism involving activation of receptors coupled to cyclic GMP production and activation of potassium channels.[12][13]

Dr. Mattson was the first to report that TNF and NF-κB can promote neuronal survival, and he went on to show that the mechanism involves up-regulation of the expression of manganese superoxide dismutase and Bcl-2, and stabilization of cellular calcium homeostasis.[14][15][16] These provocative findings led to a 180 degree turn in the view of pro-inflammatory cytokines and NF-κB in neuronal injury by establishing that activation of NF-κB in neurons is part of an adaptive response aimed at protecting the neurons.

Discoveries made in Dr. Mattson’s laboratory led to a new view of apoptotic biochemical cascades in the physiological regulation of synaptic plasticity and structural remodeling, and introduced the neuroscience field to the concept of “synaptic apoptosis”.[17] He showed that, by cleaving specific glutamate receptor subunits, caspases play important roles in regulating synaptic plasticity, an entirely new and unexpected function of apoptotic proteases.[18]

A series of findings by Dr. Mattson during the 1990s and 2000s established links between diet and the pathogenesis of neurodegenerative disorders. He has shown that intermittent fasting can increase the resistance of neurons in the brain to dysfunction and degeneration in animal models of Alzheimer's, Parkinson's and Huntington's disease and stroke.[19][20][21][22] The underlying mechanism was shown to involve increased production of neurotrophic factors and protein chaperones, suggesting an adaptive response of brain cells to the stress associated with intermittent fasting.[23] Collectively, these findings provide an example of how Dr. Mattson’s basic research into the biochemistry and biology of neuronal plasticity and death has provided information that can be directly applied to improving the human condition.

Bioenergetic Challenges, Neuroplasticity and Neuroprotection: Research in Dr. Mattson’s laboratory has revealed the importance of intermittent energetic challenges such as vigorous exercise and fasting in promoting optimal brain function and resistance of the brain to injury and age-related neurodegenerative disorders.[24] The ability of neurons to respond adaptively to mild stress is an example of hormesis, a process in which exposure of a cell or organism to a mild stress/challenge results in beneficial effects on their function and stress resistance.[25] Dr. Mattson found that neurons can respond to energetic challenges by increasing their production of: neurotrophic factors important for learning and memory, and neurogenesis (the production of new neurons from stem cells; DNA repair enzymes that prevent the accumulation of mutations; and antioxidant enzymes that enable cells to squelch free radicals.[26][27][28] His laboratory also discovered that bioenergetics challenges such as exercise can increase the number of mitochondria in neurons and can enhance the health of the mitochondria.[29][30] In related studies, several drugs that induce mild stress on mitochondria were found to be beneficial in animal models of stroke.[31][32]

Dr. Mattson’s work has revealed mechanisms by which diabetes adversely affects hippocampal plasticity and cognitive function. He showed that, in both insulin-deficient rats and insulin-resistant mice, diabetes impairs hippocampus-dependent memory, perforant path synaptic plasticity and adult neurogenesis, and the adrenal steroid corticosterone contributes to these adverse effects.[33] Changes in hippocampal plasticity and function in both models were reversed when normal physiological levels of corticosterone were maintained, suggesting that cognitive impairment in diabetes may result from glucocorticoid-mediated deficits in neurogenesis and synaptic plasticity. In a related study, Mattson showed that rats fed with a high-fat, high-glucose diet supplemented with fructose corn syrup exhibit alterations in energy and lipid metabolism similar to clinical diabetes, with elevated fasting glucose and increased cholesterol and triglycerides. Rats maintained on this diet for 8 months exhibited impaired spatial learning ability, reduced hippocampal dendritic spine density, and reduced long-term potentiation at Schaffer collateral—CA1 synapses.[34] These changes occurred concurrently with reductions in levels of BDNF in the hippocampus. Dr. Mattson also investigated whether manipulations that enhance neurotrophin levels will also restore neuronal structure and function in diabetes. He found that running wheel activity, caloric restriction, or the combination of the two treatments increased levels of BDNF in the hippocampus of diabetic mice. Enhancement of hippocampal BDNF was accompanied by increases in dendritic spine density on the secondary and tertiary dendrites of dentate granule neurons. These studies suggest that diabetes exerts detrimental effects on hippocampal structure, and that this state can be attenuated by increasing energy expenditure and decreasing energy intake.[35] The implications of these findings for cognitive aging are clear – dietary moderation and regular exercise will enhance cognitive function.

The key roles of toll-like receptors (TLRs) as mediators of the detection and responses of immune cells to invading pathogens are well known. However, Dr. Mattson recently discovered that neurons also express a subset of TLRs and that their activation promotes neuronal degeneration in experimental models of stroke and AD[36] He has also provided evidence that toll-like receptors play roles in regulating the processes of neurogenesis and neurite outgrowth, suggesting roles in neuronal plasticity.[37] TLR2 and TLR4 levels are increased in cerebral cortical neurons in response to ischemia/reperfusion injury, and the amount of brain damage and neurological deficits caused by a stroke are significantly less in mice deficient in TLR2 or -4 compared with WT control mice. Mattson found that TLR4 expression increases in neurons when exposed to Abeta or the lipid peroxidation product 4-hydroxynonenal (HNE). Neuronal apoptosis triggered by Abeta and HNE is mediated by jun N-terminal kinase (JNK); neurons from TLR4 mutant mice exhibit reduced JNK and caspase-3 activation and were protected against apoptosis induced by Abeta and HNE. Levels of TLR4 are decreased in inferior parietal cortex tissue specimens from end-stage AD patients compared to aged-matched control subjects, possibly as the result of loss of neurons expressing TLR4. These findings suggest that TLR4 signaling increases the vulnerability of neurons to Abeta and oxidative stress in AD, and identify TLR4 as a potential therapeutic target for stroke and AD.

Glucagon-like peptide-1 (GLP-1) is an endogenous insulinotropic peptide secreted from the gastrointestinal tract in response to food intake. It enhances pancreatic islet beta-cell proliferation and glucose-dependent insulin secretion, and lowers blood glucose and food intake in patients with type 2 diabetes mellitus (T2DM). A long-acting GLP-1 receptor (GLP-1R) agonist, Exenatide, is the first of this new class of antihyperglycemia drugs approved by the FDA to treat T2DM. Mattson and his colleagues at the National Institute on Aging have shown that GLP-1Rs are expressed in neurons where they are coupled to the cAMP second messenger pathway resulting in neurotrophic actions. For example, he showed that Exenatide can protect neurons from being damaged and killed by Abeta.[38] Administration of Exenatide reduced brain damage and improved functional outcome in a transient middle cerebral artery occlusion stroke model, and also protected dopaminergic neurons against degeneration, preserved dopamine levels, and improved motor function in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease.[39] Moreover, Exenatide treatment ameliorated abnormalities in peripheral glucose regulation and suppressed cellular pathology in both brain and pancreas in a mouse model of Huntington's disease.[40] The treatment also improved motor function and extended the survival time of the Huntington's disease mice. Because Exenatide improves glucose regulation and exerts direct neuroprotective actions on neurons in the brain, it and related drugs are being tested in patients with mild cognitive impairment and Alzheimer's disease.

Intermittent Fasting

Dr. Mattson’s research on animal models and human subjects has resulted in the widespread adoption of intermittent fasting as an intervention to optimize health and reduce the risk of many major chronic diseases including obesity, diabetes, cancer, asthma and other inflammatory disorders, cardiovascular disease and neurodegenerative disorders.[41][42]

Animal studies performed in Dr. Mattson’s Laboratory showed that intermittent fasting has profound beneficial effects on the body and brain including: 1) Improved glucose regulation; 2) Loss of abdominal fat with maintenance of muscle mass; 3) Reduced blood pressure and heart rate, and increased heart rate variability (similar to what occurs in trained endurance athletes; 4) Improved learning and memory and motor function; 5) Protection of neurons in the brain against dysfunction and degeneration in animal models of Alzheimer's disease, Parkinson's disease, stroke and Huntington's disease. He further discovered that intermittent fasting is beneficial for health because it imposes a challenge to cells, and those cells respond adaptively by enhancing their ability to cope with stress and resist disease.[43]

After publishing the results of two studies documenting beneficial effects of intermittent fasting in human subjects, one in asthma patients (in collaboration with Dr. James Johnson at LSU Medical Center)[44] and another in women at risk for breast cancer (in collaboration with Dr. Michelle Harvie at the University of Manchester),[45] media coverage of Dr. Mattson’s research led to a BBC documentary and a subsequent book by Dr. Michael Mosley which have informed the public throughout Europe and North America of the health benefits of intermittent fasting. In particular, a diet called the 5:2 diet, based on the studies of Drs. Harvie and Mattson has become widely popular. A person on the 5:2 diet eats normal amounts of healthy food 5 days each week and eats only one moderate size (500-600 calorie) meal 2 days each week. For many, this diet has proven easy to implement and maintain.

Phytochemical Hormesis: In 2006 Dr. Mattson proposed that the reason that vegetables, fruits, tea and coffee can improve brain health is that they contain ‘noxious’ chemicals that are produced by the plants to protect themselves from being eaten by insects and other organisms. {Mattson, M. P. and A. Cheng (2006) Neurohormetic phytochemicals: low dose toxins that induce adaptive neuronal stress responses. Trends Neurosci. 29: 632-639} Such phytochemicals, which are classified as antifeedants or natural pesticides, trigger adaptive stress responses in brain cells which can improve brain function and may increase the resistance of neurons to injury and age-related neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease. Dr. Mattson recently published an article in Scientific American that describes the evolutionary basis, molecular mechanisms and dietary implications of what he has termed ‘phytochemical hormesis’[46]

Mental Pattern Processing: A fundamental question in philosophy and neuroscience is why and how humans have greatly surpassed other species in their abilities to reason, communicate and engage in abstract thought. In 2014 Dr. Mattson published an article entitled “Superior Pattern Processing is the Essence of the Evolved Human Brain” in which he proposed that superior mental processing of patterns is the fundamental basis of all advanced capabilities of the human brain including intelligence, imagination, invention, language and the belief in imaginary entities such as gods and ghosts.[47] The expansion of the cerebral cortex during human evolution involved mostly brain regions such as the visual association cortex and prefrontal cortex that function to rapidly process visual images and make decisions accordingly. Patterns, be they real or imagined, are reinforced by emotional and social experiences, indoctrination and even psychedelic drugs. The abnormal brain function and behaviors that occur in cognitive and psychiatric disorders result from impaired or aberrant pattern processing. Dr. Mattson’s theory has important implications for understanding human intelligence, creativity and imagination, and for the development of novel approaches for reducing irrational decisions and destructive behaviors that continue to persist in individuals and radical groups throughout the world.

Personal life

Dr. Mattson lives with his wife, Joanne Mattson and is father to two children, Elliot and Emma. In his spare time, he pursues trail running, mountain biking and off-road motorcycling. Having been taught by his father DeWayne, Mark learned how to train and drive standardbred race horses (trotters and pacers), and competed on race tracks in Minnesota, Wisconsin, Iowa and Michigan during the 1970s and 1980s. In the past, he also competed as a distance runner, and was a cross country running coach at Patterson Mill High School in Bel Air, Maryland. Additionally, he is a qualified Master Gardener and enjoys animal husbandry.

Quotes

“Superior pattern processing is the essence of the evolved human brain”

“Minds are opened by wonder and closed by belief”

“Live a life guided by truth, rather than one lost in faith

“Challenges prolong life, while complacency hastens death”

“Trail running is a quintessential human pleasure”

“Nerve cells possess an innate ability to respond adaptively to intermittent challenges in ways that help them perform optimally and counteract the adversities of aging, thereby forestalling Alzheimer’s and Parkinson’s diseases”

“The human brain is particularly adept at imagination and fabrication, an ability responsible for both understanding and escaping reality”

"Imagination is the engine of creativity and the currency of religious delusions"

References

  1. ↑ "Google Scholar search". Retrieved 25 July 2013.
  2. ↑ Mattson MP (2004) Pathways towards and away from Alzheimer's disease. Nature 430:631-639
  3. ↑ Magnus T, Mattson MP (2006) Ageing and neuronal vulnerability. Nature Reviews Neuroscience 7:278-294
  4. ↑ Mattson MP et al. (1988) Outgrowth-regulating actions of glutamate in isolated hippocampal pyramidal neurons. J. Neurosci. 8:2087-2100.
  5. ↑ Mattson MP et al. (1988) Interactions between entorhinal axons and target hippocampal neurons: A role for glutamate in the development of hippocampal circuitry. Neuron 1:.865-876.
  6. ↑ Mattson MP et al. (1989) Fibroblast growth factor and glutamate: Opposing actions in the generation and degeneration of hippocampal neuroarchitecture. J. Neurosci. 9:3728-3740.
  7. ↑ Cheng B, Mattson MP (1991) NGF and bFGF protect rat and human central neurons against hypoglycemic damage by stabilizing calcium homeostasis. Neuron 7:1031-1041
  8. ↑ Mattson MP et al. (1992) β-amyloid peptides destabilize calcium homeostasis and render human cortical neurons vulnerable to excitotoxicity. J. Neurosci. 12:376-389
  9. ↑ Mark RJ et al. (1997) Amyloid β-peptide impairs glucose uptake in hippocampal and cortical neurons: involvement of membrane lipid peroxidation. J. Neurosci. 17: 1046-1054
  10. ↑ Keller JN et al. (1997) 4-hydroxynonenal, an aldehydic product of membrane lipid peroxidation, impairs glutamate transport and mitochondrial function in synaptosomes. Neuroscience 80: 685-696
  11. ↑ Guo Q et al. (1999) Increased vulnerability of hippocampal neurons to excitotoxic necrosis in presenilin-1 mutant knockin mice. Nature Medicine 5: 101-107.
  12. ↑ Mattson MP et al. (1993) Evidence for excitoprotective and intraneuronal calcium-regulating roles for secreted forms of β-amyloid precursor protein. Neuron 10:243-254
  13. ↑ Furukawa K, Barger SW, Blalock E, Mattson MP (1996) Activation of K+ channels and suppression of neuronal activity by secreted β-amyloid precursor protein. Nature 379: 74-78
  14. ↑ Cheng B, Christakos S, Mattson MP (1994) TNFs protect neurons against excitotoxic/metabolic insults and promote maintenance of calcium homeostasis. Neuron 12:139-153
  15. ↑ Barger SW et al. (1995) Tumor necrosis factors α and β protect neurons against amyloid β-peptide toxicity: evidence for involvement of a κB-binding factor and attenuation of peroxide and Ca2+ accumulation. Proc. Natl. Acad. Sci. U.S.A. 92: 9328-9332
  16. ↑ Bruce AJ, Boling W, Kindy MS, Peschon J, Kraemer PJ, Carpenter MK, Holtsberg FW, Mattson MP (1996) Altered neuronal and microglial responses to brain injury in mice lacking TNF receptors. Nature Medicine 2: 788-794
  17. ↑ (1998) Evidence for synaptic apoptosis. Exp. Neurol. 153: 35-48
  18. ↑ Glazner, G. W., S. L. Chan, C. Lu and M. P. Mattson (2000) Caspase-mediated degradation of AMPA receptor subunits: a mechanism for preventing excitotoxic necrosis and ensuring apoptosis. J. Neurosci. 20: 3641-3649
  19. ↑ Bruce-Keller, A. J., G. Umberger, R. McFall and M. P. Mattson (1999) Food restriction reduces brain damage and improves behavioral outcome following excitotoxic and metabolic insults. Ann. Neurol. 45: 8-15
  20. ↑ Anson RM, Guo Z, de Cabo R, Iyun T, Rios M, Hagepanos A, Ingram DK, Lane MA, Mattson MP (2003) Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake. PNAS. 100: 6216-6220
  21. ↑ Maswood N, Young J, Tilmont E, Zhang Z, Gash DM, Gerhardt GA, Grondin R, Roth GS, Mattison J, Lane MA, Carson RE, Cohen RM, Mouton PR, Quigley C, Mattson MP, Ingram DK (2004) Caloric restriction increases GDNF levels and attenuates neurochemical and behavioral deficits in a primate model of Parkinson's disease. PNAS 101:18171-18176
  22. ↑ Duan, W., Z. Guo, H. Jiang, M. Ware, X. J. Li and M. P. Mattson (2003) Dietary restriction normalizes glucose metabolism and BDNF levels, slows disease progression and increases survival in Huntingtin mutant mice. Proc. Natl. Acad. Sci. U.S.A. 100: 2911-2916
  23. ↑ Mattson MP (2012) Energy intake and exercise as determinants of brain health and vulnerability to injury and disease. Cell Metabolism 16: 706-722
  24. ↑ Stranahan AM, Mattson MP (2012) Recruiting adaptive cellular stress responses for successful brain aging. Nature Rev. Neurosci. 13: 209-216
  25. ↑ Mattson MP (2008) Hormesis defined. Ageing Res Rev. 7:1-7
  26. ↑ Arumugam TV, Phillips TM, Cheng A, Morrell CH, Mattson MP, Wan R (2010) Age and energy intake interact to modify cell stress pathways and stroke outcome. Ann Neurol. 67:41-52
  27. ↑ Keller JN, Kindy MS, Holtsberg FW, St Clair DK, Yen HC, Germeyer A, Steiner SM, Bruce-Keller AJ, Hutchins JB, Mattson MP. (1998) Mitochondrial manganese superoxide dismutase prevents neural apoptosis and reduces ischemic brain injury: suppression of peroxynitrite production, lipid peroxidation, and mitochondrial dysfunction. J Neurosci. 18:687-97
  28. ↑ Yang JL, Lin YT, Chuang PC, Bohr VA, Mattson MP (2014). BDNF and exercise enhance neuronal DNA repair by stimulating CREB-mediated production of apurinic/apyrimidinic endonuclease 1. Neuromolecular Med. 16:161-74
  29. ↑ Cheng A, Wan R, Yang JL, Kamimura N, Son TG, Ouyang X, Luo Y, Okun E, Mattson MP (2012) Involvement of PGC-1α in the formation and maintenance of neuronal dendritic spines. Nature Commun. Dec 4;3:1250. doi: 10.1038/ncomms2238
  30. ↑ Cheng A, Yang Y, Zhou Y, Maharana C, Lu D, Peng W, Liu Y, Wan R, Marosi K, Misiak M, Bohr VA, Mattson MP (2015) Mitochondrial SIRT3 mediates adaptive responses of neurons to exercise, and metabolic and excitatory challenges. Cell Metabolism 2015 Nov 18. pii: S1550-4131(15)00529-X
  31. ↑ Liu D, Lu C, Wan R, Auyeung WW, Mattson MP. (2002) Activation of mitochondrial ATP-dependent potassium channels protects neurons against death in experimental models relevant to stroke and neurodegenerative disorders by a mechanism involving suppression of Bax translocation and cytochrome c release. J Cereb Blood Flow Metab. 22:431-43
  32. ↑ Liu D, Zhang Y, Gharavi R, Park HR, Lee J, Siddiqui S, Telljohann R, Nassar MR, Cutler RG, Becker KG, Mattson MP. (2015) The mitochondrial uncoupler DNP triggers brain cell mTOR signaling network reprogramming and CREB pathway up-regulation. J Neurochem. 134:677-92
  33. ↑ Stranahan AM, Arumugam TV, Cutler RG, Lee K, Egan JM, Mattson MP (2008) Diabetes impairs hippocampal function via glucocorticoid-mediated effects on new and mature neurons. Nature Neurosci. 11:309-317
  34. ↑ Stranahan, A. M., E. D. Norman, K. Lee, R. G. Cutler, R. Telljohann, J. M. Egan and M. P. Mattson (2008) Diet-induced insulin resistance impairs hippocampal synaptic plasticity and cognition in middle-aged rats. Hippocampus 18: 1085-1088
  35. ↑ Stranahan, A. M., K. Lee, B. Martin, E. Golden, R. G. Cutler and M. P. Mattson (2009) Voluntary exercise and caloric restriction enhance hippocampal dendritic spine density and BDNF levels in diabetic mice. Hippocampus 19: 951-961
  36. ↑ Tang SC, Arumugam TV, Xu X, Cheng A, Mughal MR, Jo DG, Lathia JD, Siler DA, Chigurupati S, Ouyang X, Magnus T, Camandola S, Mattson MP. (2007) Pivotal role for neuronal Toll-like receptors in ischemic brain injury and functional deficits. PNAS 104:13798-13803
  37. ↑ Okun, E., K. Griffioen, B. Barak, N. J. Roberts, K. Castro, M. Pitta, A. Cheng, M. R. Mughal, R. Wan, U. Ashery and M. P. Mattson (2010) Toll-like receptor 3 inhibits memory retention and constrains adult hippocampal neurogenesis. Proc. Natl. Acad. Sci. U.S.A. 107:15625-15630
  38. ↑ 2010) GLP-1 receptor stimulation reduces amyloid β-peptide accumulation and cytotoxicity in cellular and animal models of Alzheimer’s disease. J. Alzheimer’s Dis. 19: 1205-1219
  39. ↑ (2009). GLP-1 receptor stimulation preserves primary cortical and dopaminergic neurons in cellular and rodent models of stroke and Parkinsonism. Proc. Natl. Acad. Sci. U.S.A. 106: 1285-1290
  40. ↑ (2009) Exendin-4 improves glycemic control, ameliorates brain and pancreatic pathologies, and extends survival in a mouse model of Huntington’s disease. Diabetes 58: 318-328
  41. ↑ Longo VD, Mattson MP (2014) Fasting: molecular mechanisms and clinical applications. Cell Metabolism 19:181-192
  42. ↑ Mattson, M. P., D. B. Allison, L. Fontana, M. Harvie, V. D. Longo, W. J. Malaisse, M. Mosley, L. Notterpek, E. Ravussin, F. A. J. L. Scheer, T. Seyfried, K. Varady and S. Panda (2014) Meal frequency and timing in health and disease. Proc. Natl. Acad. Sci. U.S.A. 111: 16647–16653
  43. ↑ Mattson, M. P. (2015) Lifelong brain health is a lifelong challenge: from evolutionary principles to empirical evidence. Ageing Res. Rev. 20: 37-45
  44. ↑ Johnson, J. B., W. Summer, R. G. Cutler, B. Martin, D. H. Hyun, V. D. Dixit, M. Pearson, M. Nassar, S. Maudsley, O. Carlson, S. John, D. R. Laub and M. P. Mattson (2007) Alternate day calorie restriction improves clinical findings and reduces markers of oxidative stress and inflammation in overweight adults with moderate asthma. Free Rad. Biol. Med. 42: 665-674
  45. ↑ Harvie M et al. (2011) The effects of intermittent and continuous energy restriction on weight loss, and metabolic disease risk markers: a randomized trial in young overweight women. Int. J. Obesity. 35: 714-727
  46. ↑ Mattson MP (2015) What doesn’t kill you… Scientific American 313: 40-45
  47. ↑ Mattson, M. P. (2014) Superior pattern processing is the essence of the evolved human brain. Front. Neurosci. Published online, 22 Aug; http://journal.frontiersin.org/Journal/10.3389/fnins.2014.00265/full

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