Brain‐derived neurotrophic factor as a regulator of systemic and brain energy metabolism and cardiovascular health

Abstract

Overweight sedentary individuals are at increased risk for cardiovascular disease, diabetes, and some neurological disorders. Beneficial effects of dietary energy restriction (DER) and exercise on brain structural plasticity and behaviors have been demonstrated in animal models of aging and acute (stroke and trauma) and chronic (Alzheimer's and Parkinson's diseases) neurological disorders. The findings described later, and evolutionary considerations, suggest brain‐derived neurotrophic factor (BDNF) plays a critical role in the integration and optimization of behavioral and metabolic responses to environments with limited energy resources and intense competition. In particular, BDNF signaling mediates adaptive responses of the central, autonomic, and peripheral nervous systems from exercise and DER. In the hypothalamus, BDNF inhibits food intake and increases energy expenditure. By promoting synaptic plasticity and neurogenesis in the hippocampus, BDNF mediates exercise‐ and DER‐induced improvements in cognitive function and neuroprotection. DER improves cardiovascular stress adaptation by a mechanism involving enhancement of brainstem cholinergic activity. Collectively, findings reviewed in this paper provide a rationale for targeting BDNF signaling for novel therapeutic interventions in a range of metabolic and neurological disorders.

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    Roberge MC, Messier C, Staines WA, Plamondon H. Food restriction induces long-lasting recovery of spatial memory deficits following global ischemia in delayed matching and non-matching-to-sample radial arm maze tasks. Neuroscience. 2008;156:11-29.

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     Rich NJ, Van Landingham JW, Figueiroa S, et al. Chronic caloric restriction reduces tissue damage and improves spatial memory in a rat model of traumatic brain injury. J. Neurosci. Res. 2010;88:2933-2939.

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     Mattson MP, Lovell MA, Furukawa K, Markesbery WR. Neurotrophic factors attenuate glutamate-induced accumulation of peroxides, elevation of intracellular Ca2 +concentration, and neurotoxicity and increase antioxidant enzyme activities in hippocampal neurons. J. Neurochem. 1995;65:1740-1751.

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     Almeida RD, Manadas BJ, Melo CV, et al. Neuroprotection by BDNF against glutamate-induced apoptotic cell death is mediated by ERK and PI3-kinase pathways. Cell Death Differ. 2005;12:1329-1343.

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     Yang JL, Tadokoro T, Keijzers G, et al. Neurons efficiently repair glutamate-induced oxidative DNA damage by a process involving CREB-mediated up-regulation of apurinic endonuclease 1. J. Biol. Chem. 2010;285:28191-28199.

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     Lu B, Figurov A. Role of neurotrophins in synapse development and plasticity. Rev. Neurosci. 1997;8:1-12.

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     Kuczewski N, Porcher C, Lessmann V, et al. Activity-dependent dendritic release of BDNF and biological consequences. Mol. Neurobiol. 2009;39:37-49.

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     Cowansage KK, LeDoux JE, Monfils M-H. Brain-derived neurotrophic factor: a dynamic gatekeeper of neural plasticity. Curr. Mol. Pharmacol. 2010;3:12-29.

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     Mattson MP, Wan RQ. Neurotrophic factors in autonomic nervous system plasticity and dysfunction. Neuromol. Med. 2008;10:157-168.

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108. 108.

     Schmidt HD, Duman RS. The role of neurotrophic factors in adult hippocampal neurogenesis, antidepressant treatments and animal models of depressive-like behavior. Behav. Pharmacol. 2007;18:391-418.

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     Lu Y, Christian K, Lu B. BDNF: a key regulator for protein synthesis-dependent LTP and long-term memory? Neurobiol. Learn Mem. 2008;89:312-323.

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     Minichiello L. TrkB signalling pathways in LTP and learning. Nat. Rev. Neurosci. 2009;10:850-860.

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     Castillo-Quan JI, Barrera-Buenfil DJ, Pérez-Osorio JM, Alvarez-Cervera FJ. Depression and diabetes: from epidemiology to neurobiology. Rev. Neurol. 2010;51:347-59.

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     Nilsson LG, Nilsson E. Overweight and cognition. Scand. J. Psychol. 2009;50:660-667.

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     Sabia S, Kivimaki M, Shipley MJ, et al. Body mass index over the adult life course and cognation in late midlife: the Whitehall II Cohort Study. Am. J. Clin. Nutr. 2009;89:601-607.

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     Kodl C, Seaquist ER. Cognitive dysfunction and diabetes mellitus. Endocr. Rev. 2008;29:494-511.

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115. 115.

     Hölscher C. Diabetes as a risk factor for Alzheimer's disease: insulin signalling impairment in the brain as an alternative model of Alzheimer's disease. Biochem. Soc. Trans. 2011;39:891-897.

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     Kopf D, Frölich L. Risk of incident Alzheimer's disease in diabetic patients: a systematic review of prospective trials. J. Alzheimers Dis. 2009;16:677-685.

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     Muoio DM, Newgard CB. Obesity-related derangements in metabolic regulation. Ann. Rev. Biochem. 2006;75:367-401.

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     Qiu C, De Ronchi D, Fratiglioni L. The epidemiology of the dementias: an update. Curr. Opin. Psychiat. 2007;20:380-385.

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     Stranahan AM, Mattson MP. Impact of energy intake and expenditure on neuronal plasticity. Neuromol. Med. 2008;10:209-218.

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120. 120.

     Greenwood CE, Winocur G. Cognitive impairment in rats fed high-fat diets: a specific effect of saturated fatty-acid intake. Behav. Neurosci. 1996;110:451-459.

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     Granholm AC, Bimonte-Nelson HA, Moore AB, et al. Effects of a saturated fat and high cholesterol diet on memory and hippocampal morphology in the middle-aged rat. J. Alzheimers Dis. 2008;14:133-145.

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     Stranahan AM, Norman ED, Lee K, et al. Diet-induced insulin resistance impairs hippocampal synaptic plasticity and cognition in middle-aged rats. Hippocampus. 2008a;18:1085-1088.

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     Shi L, Adams MM, Linville MC, et al. Caloric restriction eliminates the aging-related decline in NMDA and AMPA receptor subunits in the rat hippocampus and induces homeostasis. Exp. Neurol. 2007;206:70-79.

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     Gomez-Pinilla F, Vaynman S, Ying Z. Brain-derived neurotrophic factor functions as a metabotrophin to mediate the effects of exercise on cognition. Eur. J. Neurosci. 2008;28:2278-2287.

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125. 125.
     2-Deoxy-D-Glucose Treatment Induces Ketogenesis, Sustains Mitochondrial Function, and Reduces Pathology in Female Mouse Model of Alzheimer's Disease · 2011

     No notice
126. 126.

     Maalouf M, Rho JM, Mattson MP. The neuroprotective properties of calorie restriction, the ketogenic diet, and ketone bodies. Brain Res. Rev. 2009;59:293-315.

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     Robinet C, Pellerin L. Brain-derived neurotrophic factor enhances the expression of the monocarboxylate transporter 2 through translational activation in mouse cultured cortical neurons. J. Cereb. Blood Flow Metab. 2010;30:286-298.

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128. 128.

     Burkhalter J, Fiumelli H, Allaman I, et al. Brain-derived neurotrophic factor stimulates energy metabolism in developing cortical neurons. J. Neurosci. 2003;23:8212-8220.

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     Zhang J, Wang Y, Chi Z, et al. The AAA+ ATPase Thorase regulates AMPA receptor-dependent synaptic plasticity and behavior. Cell. 2011;145:284-299.

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     Abraham WC, Williams JM. LTP maintenance and its protein synthesis-dependence. Neurobiol. Learn Mem. 2008;89:260-268.

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     Wang C, Bomberg E, Billington C, et al. Brain-derived neurotrophic factor in the hypothalamic paraventricular nucleus increases energy expenditure by elevating metabolic rate. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2007;293:R992-1002.

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     Cao L, Choi EY, Liu X, et al. White to brown fat phenotypic switch induced by genetic and environmental activation of a hypothalamic-adipocyte axis. Cell Metab. 2011;14:324-338.

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     Griffioen KJ, Wan R, Brown TR, et al. Aberrant heart rate and brainstem BDNF signaling in a mouse model of Huntington's disease. Neurobiol. Aging. 2011.

     Not in our library10.1016/j.neurobiolaging.2011.11.030

Cited by papers we hold 2

• The effects of fasting on physiological status and gene expression; an overview · 2015
  Not checked
• Effects of Diet on Brain Plasticity in Animal and Human Studies: Mind the Gap · 2014
  No notice

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