Alcohol and Brain-Derived Neurotrophic Factor (BDNF)

  1. Martín-González, Candelaria 1
  2. González-Arnay, Emilio 1
  3. Fernández-Rodríguez, Camino María 1
  4. García-Rodríguez, Alen
  5. González-Reimers, Emilio 1
  1. 1 Universidad de La Laguna
    info

    Universidad de La Laguna

    San Cristobal de La Laguna, España

    ROR https://ror.org/01r9z8p25

Book:
Handbook of Substance Misuse and Addictions

Publisher: Springer

ISBN: 9783030679286 9783030679286

Year of publication: 2021

Pages: 1-27

Type: Book chapter

DOI: 10.1007/978-3-030-67928-6_182-1 GOOGLE SCHOLAR lock_openOpen access editor

Sustainable development goals

Abstract

Brain-derived neurotrophic factor (BDNF) is a neurotrophin, heavily involved in hippocampal neurogenesis, dendritogenesis, synaptogenesis, and synaptic plasticity and stability, therefore playing a key role in learning process and memory formation. These effects depend on the mature form of the molecule that binds to the TRKB receptor. The pro-molecule, which contains both the mature form and the BDNF prodomain, induces apoptosis and long-term depression after binding to the p75 NTR receptor. Mature BDNF plays major roles in addiction, increasing after acute slight to moderate drinking, but exerting a regulatory effect on alcohol drinking. Chronic ingestion and/or inebriation decrease BDNF expression and may disrupt this homeostatic mechanism. In addition to the neurologic effects, BDNF is a major regulator of energy balance, since it decreases appetite and increases thermogenesis, fatty acid oxidation, and glucose uptake. Exercise, learning, episodic fasting, and environmental enrichment increase BDNF expression and secretion, lending support to the beneficial effect of exercise on the maintenance of cognitive functions. It keeps an inverse relationship with inflammation. BDNF muscle expression increases after exercise and optimizes the metabolic status of the muscle fiber. BDNF levels are reduced in various neurodegenerative disorders. The frequently observed brain atrophy, muscle atrophy-impeding exercise, and inflammatory status observed in excessive drinkers may alter BDNF expression and secretion, although some disparate results have been reported. The possible pathogenetic role of BDNF on muscle and/or brain atrophy in these patients needs future research.

Bibliographic References

  • An JJ, Gharami K, Liao G-Y et al (2008) Distinct role of long 3' UTR BDNF mRNA in spine morphology and synaptic plasticity in hippocampal neurons. Cell 134:175–187. https://doi.org/10.1016/j.cell.2008.05.045
  • Anand, Prakash Huaibo, Zhang Subhash C., Pandey (2008) Innate Differences in the Expression of Brain-Derived Neurotrophic Factor in the Regions Within the Extended Amygdala Between Alcohol Preferring and Nonpreferring Rats. Alcoholism: Clinical and Experimental Research 32(6):909–920. https://doi.org/10.1111/j.1530-0277.2008.00650.x
  • Anastasia A, Deinhardt K, Chao MV et al (2013) Val66Met polymorphism of BDNF alters prodomain structure to induce neuronal growth cone retraction. Nat Commun 4:2490. https://doi.org/10.1038/ncomms3490
  • Barde YA, Edgar D, Thoenen H (1982) Purification of a new neurotrophic factor from mammalian brain. EMBO J 1:549–553
  • Bednarek E, Caroni P (2011) β-Adducin is required for stable assembly of new synapses and improved memory upon environmental enrichment. Neuron 69:1132–1146.5
  • Bohnsack JP, Teppen T, Kyzar EJ, Dzitoyeva S, Pandey SC (2019) The lncRNA BDNF-AS is an epigenetic regulator in the human amygdala in early onset alcohol use disorders. Transl Psychiatry 9:34. https://doi.org/10.1038/s41398-019-0367-z
  • Braken BK, Turrigiano GG (2009) Experience dependent regulation of TRK-B isoforms in rodent visual cortex. Dev Neurobiol 69:267–278
  • Bronfman FC, Fainzilber M (2004) Multi-tasking by the p75 neurotrophin receptor: sortilin things out? EMBO Rep 5:867–871
  • Cao L, Choi EY, Liu X et al (2011) White to brown fat phenotypic switch induced by genetic and environmental activation of a hypothalamic-adipocyte axis. Cell Metab 14:324–338. https://doi.org/10.1016/j.cmet.2011.06.020
  • Chapman TR, Barrientos RM, Ahrendsen JT et al (2012) Aging and infection reduce expression of specific brain-derived neurotrophic factor mRNAs in hippocampus. Neurobiol Aging 33(832):e1–e14. https://doi.org/10.1016/j.neurobiolaging.2011.07.015
  • Chen MJ, Russo-Neustadt AA (2009) Running exercise-induced up-regulation of hippocampal brain-derived neurotrophic factor is CREB-dependent. Hippocampus 19:962–972. https://doi.org/10.1002/hipo.20579
  • Chen ZY, Ieraci A, Teng H et al (2005) Sortilin controls intracellular sorting of brain-derived neurotrophic factor to the regulated secretory pathway. J Neurosci 25:6156–6166. https://doi.org/10.1523/JNEUROSCI.1017-05.2005
  • Cheng PL, Song A-I, Wong YH, Wang S, Zahng X, Poo MM (2011) Self-amplifying autocrine actions of BDNF in axon development. Proc Natl Acad Sci U S A 108:18430–18435. https://doi.org/10.1073/pnas.1115907108
  • Cohen-Cory S, Kidane AH, Shirkey NJ, Marshak S (2010) Brain derived neurotrophic factor and the development of structural neuronal connectivity. Dev Neurobiol 70:271–288
  • Costa MA, Girard M, Dalmay F, Malauzat D (2011) Brain-derived neurotrophic factor serum levels in alcohol-dependent subjects 6 months after alcohol withdrawal. Alcohol Clin Exp Res 35:1966–1973. https://doi.org/10.1111/j.1530-0277.2011.01548.x
  • Cotman CW, Berchtold NC (2002) Exercise: a behavioral intervention to enhance brain health and plasticity. Trends Neurosci 25:295–301
  • Cunha C, Brambilla R, Thomas KL (2010) A simple role for BDNF in learning and memory? Front Mol Neurosci 3:1. https://doi.org/10.3389/neuro.02.001.2010
  • D’Sa C, Dileone RJ, Anderson GM, Sinha R (2012) Serum and plasma brain-derived neurotrophic factor (BDNF) in abstinent alcoholics and social drinkers. Alcohol 46:253–259. https://doi.org/10.1016/j.alcohol.2011.12.001
  • Darcq E, Warnault V, Phamluong K, Besserer GM, Liu F, Ron D (2015) MicroRNA-30a-5p in the prefrontal cortex controls the transition from moderate to excessive alcohol consumption. Mol Psychiatry 20:1219–1231. https://doi.org/10.1038/mp.2014.120
  • Deinhart K, Chao MV (2014) Shaping neurons: long and short range effects of mature and proBDNF signalling upon neuronal structure. Neuropharmacology 76:603–609
  • Di Liegro CM, Schiera G, Proia P, Di Liegro I (2019) Physical activity and brain health. Genes (Basel) 10(9):720. https://doi.org/10.3390/genes10090720
  • Dincheva I, Glatt CE, Lee FS (2012) Impact of the BDNF Val66Met polymorphism on cognition: implications for behavior genetics. Neuroscientist 18:439–451
  • Dowlati Y, Herrmann N, Swardfager W et al (2010) A meta-analysis of cytokines in major depression. Biol Psychiatry 67(5):446–457. https://doi.org/10.1016/j.biopsych.2009.09.033
  • Duman RS, Deyama S, Fogaça MV (2021) Role of BDNF in the pathophysiology and treatment of depression: activity-dependent effects distinguish rapid-acting antidepressants. Eur J Neurosci 53:126–139. https://doi.org/10.1111/ejn.14630
  • Epp JR, Chow C, Galea LM (2013) Hippocampus-dependent learning influences hippocampal neurogenesis. Front Neurosci 7. Published: 16 April 2013. https://doi.org/10.3389/fnins.2013.00057
  • Fan G, Hutnick L (2005) Methyl-CpG binding proteins in the nervous system. Cell Res 15:255–261
  • Ferris LT, Williams JS, Shen CL (2007) The effect of acute exercise on serum brain-derived neurotrophic factor levels and cognitive function. Med Sci Sports Exerc 39:728–734
  • Fujimura H, Altar CA, Chen R et al (2002) Brain-derived neurotrophic factor is stored in human platelets and released by agonist stimulation. Thromb Haemost 87:728–734
  • Fulgenzi G, Hong Z, Tomassoni-Ardori F et al (2020) Novel metabolic role for BDNF in pancreatic β-cell insulin secretion. Nat Commun 11:1950. https://doi.org/10.1038/s41467-020-15833-5
  • Geisel O, Hellweg R, Müller CA (2016) Serum levels of brain-derived neurotrophic factor in alcohol-dependent patients receiving high-dose baclofen. Psychiatry Res 240:177–180. https://doi.org/10.1016/j.psychres.2016.04.007
  • Genzer Y, Chapnik N, Froy O (2017) Effect of brain-derived neurotrophic factor (BDNF) on hepatocyte metabolism. Int J Biochem Cell Biol 88:69–74. https://doi.org/10.1016/j.biocel.2017.05.008
  • Gonzalez A, Moya-Alvarado G, González-Billault C, Bronfman FC (2016) Cellular and molecular mechanisms regulating neuronal growth by brain-derived neurotrophic factor. Cytoskeleton 73:612–628
  • Hempstead BL (2015) Brain derived neurotrophic factor: three ligands, many actions. Trans Am Clin Climatol Assoc 126:9–19
  • Huang M-C, Chen C-H, Chen C-H et al (2008) Alterations of serum brain-derived neurotrophic factor levels in early alcohol withdrawal. Alcohol Alcohol 43:241–245. https://doi.org/10.1093/alcalc/agm172
  • Jeanblanc J, Logrip ML, Janak PH, Ron D (2013) BDNF-mediated regulation of ethanol consumption requires the activation of the MAP kinase pathway and protein synthesis. Eur J Neurosci 37:607–612. https://doi.org/10.1111/ejn.12067
  • Joe K-H, Kim Y-K, Kim T-S et al (2007) Decreased plasma brain-derived neurotrophic factor levels in patients with alcohol dependence. Alcohol Clin Exp Res 31(11):1833–1838. https://doi.org/10.1111/j.1530-0277.2007.00507.x
  • John F, Bishop Gregory P, Mueller M.Maral, Mouradian (1994) Alternate 5′ exons in the rat brain-derived neurotrophic factor gene: differential patterns of expression across brain regions. Molecular Brain Research 26(1–2):225–232. https://doi.org/10.1016/0169-328X(94)90094-9
  • Joshua J, Park Niamh X, Cawley Y. Peng, Loh (2008) A bi-directional carboxypeptidase E-driven transport mechanism controls BDNF vesicle homeostasis in hippocampal neurons. Molecular and Cellular Neuroscience 39(1):63–73. https://doi.org/10.1016/j.mcn.2008.05.016
  • Kernie SG, Liebl DJ, Parada LF (2000) BDNF regulates eating behavior and locomotor activity in mice. EMBO J 19:1290–1300. https://doi.org/10.1093/emboj/19.6.1290
  • Kim T-K, Hemberg M, Gray JM (2015) Enhancer RNAs: a class of long noncoding RNAs synthesized at enhancers. Cold Spring Harb Perspect Biol 7:a018622. https://doi.org/10.1101/cshperspect.a018622
  • Klein AB, Williamson R, Santini MA et al (2011) Blood BDNF concentrations reflect brain-tissue BDNF levels across species. Int J Neuropsychopharmacol 14:347–353. https://doi.org/10.1017/S1461145710000738
  • Koob GF, Volkow ND (2016) Neurobiology of addiction: a neurocircuitry analysis. Lancet Psychiatry 3:760–773. https://doi.org/10.1016/S2215-0366(16)00104-8
  • Kowianski P, Lietzau G, Czuba E, Waskow M, Steliga A, Morys J (2018) BDNF: a key factor with multipotent impact on brain signaling and synaptic plasticity. Cell Mol Neurobiol 38:579–593
  • Krabbe KS, Nielsen AR, Krogh-Madsen R et al (2007) Brain-derived neurotrophic factor (BDNF) and type 2 diabetes. Diabetologia 50:431–438
  • Kwon M, Fernández JR, Zegarek GF, Lo SB, Firestein BL (2011) BDNF-promoted increases in proximal dendrites occur via CREB-dependent transcriptional regulation of cypin. J Neurosci 31:9735–9745
  • Kyzar EJ, Zhang H, Pandey SC (2019) Adolescent alcohol exposure epigenetically suppresses amygdala arc enhancer RNA expression to confer adult anxiety susceptibility. Biol Psychiatry 85:904–914. https://doi.org/10.1016/j.biopsych.2018.12.021
  • Lapchak PA, Hefti F (1992) BDNF and NGF treatment in lesioned rats: effects on cholinergic function and weight gain. Neuroreport 3:405–408. https://doi.org/10.1097/00001756-199205000-00007
  • Lee R, Kermani P, Teng KK, Hempstead BL (2001) Regulation of cell survival by secreted proneurotrophins. Science 294:1945–1948
  • Lee BC, Choi I-G, Kim Y-K et al (2009) Relation between plasma brain-derived neurotrophic factor and nerve growth factor in the male patients with alcohol dependence. Alcohol 43:265–269. https://doi.org/10.1016/j.alcohol.2009.04.003
  • Liu Y, Zhou LJ, Wang J et al (2017) TNF-α differentially regulates synaptic plasticity in the hippocampus and spinal cord by microglia-dependent mechanisms after peripheral nerve injury. J Neurosci 37(4):871–881. https://doi.org/10.1523/JNEUROSCI.2235-16.2016
  • Logrip ML, Barak S, Warnault V, Ron D (2015) Corticostriatal BDNF and alcohol addiction. Brain Res 1628(Pt A):60–67. https://doi.org/10.1016/j.brainres.2015.03.025
  • Lonze BE, Ginty DD (2002) Function and regulation of CREB family transcription factors in the nervous system. Neuron 35:605–623. https://doi.org/10.1016/s0896-6273(02)00828-0
  • Lu B, Pand PT, Woo NH (2005) The Yin and Yang of neurotrophin action. Nat Rev Neurosci 6:603–614
  • Mao CP, Bai ZL, Zhang XN, Zhang QJ, Zhang L (2016) Abnormal subcortical brain morphology in patients with knee osteoarthritis: a cross-sectional study. Front Aging Neurosci 8:3. https://doi.org/10.3389/fnagi.2016.00003
  • Marmigère F, Givalois L, Rage F, Arancibia S, Tapia-Arancibia L (2003) Rapid induction of BDNF expression in the hippocampus during immobilization stress challenge in adult rats. Hippocampus 13:646–655. https://doi.org/10.1002/hipo.10109
  • Marosi K, Mattson MP (2014) DBNF mediates adaptive brain and body responses to energetic challenges. Trends Endocrinol Metab 25:89–98. https://doi.org/10.1016/j.tem.2013.10.006.6
  • Martín-González C, Romero-Acevedo L, Fernández-Rodríguez CM et al (2020) Brain-derived neurotrophic factor among patients with alcoholism. CNS Spectr 19:1–6. https://doi.org/10.1017/S1092852920001431
  • Matthews VB, Aström MB, Chan MHS et al (2009) Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase. Diabetologia 52:1409–1418. https://doi.org/10.1007/s00125-009-1364-1
  • Moon HY, Becke A, Berron D et al (2016) Running-induced systemic Cathepsin B secretion is associated with memory function. Cell Metab 24:332–340. https://doi.org/10.1016/j.cmet.2016.05.025
  • Moonat S, Pandey SC (2012) Stress, epigenetics, and alcoholism. Alcohol Res 34(4):495–505
  • Moonat S, Starkman BG, Sakharkar A, Pandey S (2010) Neuroscience of alcoholism: molecular and cellular mechanisms. Cell Mol Life Sci 67:73–88. https://doi.org/10.1007/s00018-009-0135-y
  • Moonat S, Sakharkar AJ, Zhang H, Pandey SC (2011) The role of amygdaloid brain-derived neurotrophic factor, activity-regulated cytoskeleton-associated protein and dendritic spines in anxiety and alcoholism. Addict Biol 16:238–250. https://doi.org/10.1111/j.1369-1600.2010.00275.x
  • Nagappan G, Zaltsev E, Senatorov VV, Yang J, Hempstead BL, Lu B (2009) Control of extracellular claevage of proBDNF by high frequency neuronal activity. Proc Natl Acad Sci 106:1267–1272
  • Nilsson J, Ekblom O, Ekblom M et al (2020) Acute increases in brain-derived neurotrophic factor in plasma following physical exercise relates to subsequent learning in older adults. Sci Rep 10:4395. https://doi.org/10.1038/s41598-020-60124-0
  • Noble EE, Billington CJ, Colz CM, Wang CF (2011) The lighter side of BDNF. Am J Physiol Regul Integr Comp Physiol 300:R1053–R1069
  • Notaras M, van den Buuse M (2019) Brain-derived neurotrophic factor (BDNF): novel insights into regulation and genetic variation. Neuroscientist 25:434–454. https://doi.org/10.1177/1073858418810142
  • Novkovic T, Mittmann T, Manahan-Vaughan D (2015) BDNF contributes to the facilitation of hippocampal synaptic plasticity and learning enabled by environmental enrichment. Hippocampus 25:1–15
  • Numakawa T, Odaka H, Adachi N (2018) Actions of brain-derived neurotrophic factor in the neurogenesis and neuronal function, and its involvement in the pathophysiology of brain diseases. Int J Mol Sci 19:3650. https://doi.org/10.3390/ijms19113650
  • Nyborg AC, Ladd TB, Zwizinski CW, Lah JJ, Golde TE (2006) Sortilin, SorCS1b, and SorLA Vps10p sorting receptors, are novel gamma-secretase substrates. Mol Neurodegener 1:3. https://doi.org/10.1186/1750-1326-1-3
  • Ornell F, Hansen F, Schuch FB et al (2018) Brain-derived neurotrophic factor in substance use disorders: a systematic review and meta-analysis. Drug Alcohol Depend 193:91–103. https://doi.org/10.1016/j.drugalcdep.2018.08.036
  • Palmisano M, Pandey SC (2017) Epigenetic mechanisms of alcoholism and stress-related disorders. Alcohol 60:7–18. https://doi.org/10.1016/j.alcohol.2017.01.001
  • Pandey SC, Sakharkar AJ, Tang L, Zhang H (2015) Potential role of adolescent alcohol exposure-induced amygdaloid histone modifications in anxiety and alcohol intake during adulthood. Neurobiol Dis 82:607–619
  • Pandey SC, Kyzar EJ, Zhang H (2017) Epigenetic basis of the dark side of alcohol addiction. Neuropharmacology 122:74–84. https://doi.org/10.1016/j.neuropharm.2017.02.002
  • Pollock GS, Vernon E, Forbes ME, Yan Q, Ma YT, Hsieh T, Robichon R, Frost DO, Johnson JE (2001) Effects of early visual experience and diurnal rhythms on BDNF mRNA and protein levels in the visual system, hippocampus, and cerebellum. J Neurosci 21(11):3923–3931. https://doi.org/10.1523/JNEUROSCI.21-11-03923.2001
  • Pruunsild P, Kazantseva A, Aid T, Palm K, Timmusk T (2007) Dissecting the human BDNF locus: bidirectional transcription, complex splicing, and multiple promoters. Genomics 90:397–406. https://doi.org/10.1016/j.ygeno.2007.05.004
  • Qin L, Wu X, Block ML et al (2007) Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. Glia 55:453–462. https://doi.org/10.1002/glia.20467
  • Renthal W, Nestler EJ (2008) Epigenetic mechanisms in drug addiction. Trends Mol Med 14:341–350. https://doi.org/10.1016/j.molmed.2008.06.004
  • Ronald S, Duman Nanxin, Li (2012) A neurotrophic hypothesis of depression: role of synaptogenesis in the actions of NMDA receptor antagonists. Philosophical Transactions of the Royal Society B: Biological Sciences 367(1601):2475–2484. https://doi.org/10.1098/rstb.2011.0357
  • Roskoski R (2012) ERK1/2 MAP kinases: structure, function, and regulation. Pharmacol Res 66(2):105–143. https://doi.org/10.1016/j.phrs.2012.04.005
  • Sasi M, Vignoli B, Canossa M, Blum R (2017) Neurobiology of local and intercellular BDNF signaling. Pflugers Arch-Eur J Physiol 469:593–610
  • Spielman LJ, Gibson DL, Klegeris A, Spielman LJ et al (2017) Incretin hormones regulate microglia oxidative stress, survival and expression of trophic factors. Eur J Cell Biol 96(3):240–253. https://doi.org/10.1016/j.ejcb.2017.03.004
  • Starkman BG, Sakharkar AJ, Pandey SC (2012) Epigenetics-beyond the genome in alcoholism. Alcohol Res 34:293–305
  • Steven A, Friedrich M, ,Jank P, et al What turns CREB on? And off? And why does it matter? Cell Mol Life Sci 2020; 77(20): 4049–4067
  • Tien NW, Kerschensteiner D (2018) Homeostatic plasticity in neural development. Neural Dev 13:9. https://doi.org/10.1186/s13064-018-0105-x
  • Tongiorgi E, Righi M, Cattaneo A (1997) Activity-dependent dendritic targeting of BDNF and TrkB mRNAs in hippocampal neurons. J Neurosci 17:9492–9505. https://doi.org/10.1523/JNEUROSCI.17-24-09492.1997
  • Tõnis, Timmusk Kaia, Palm Madis, Metsis Tõnu, Reintam Viiu, Paalme Mart, Saarma Håkan, Persson (1993) Multiple promoters direct tissue-specific expression of the rat BDNF gene. Neuron 10(3):475–489. https://doi.org/10.1016/0896-6273(93)90335-O
  • Tsankova N, Renthal W, Kumar A, Nestler EJ (2007) Epigenetic regulation in psychiatric disorders. Nat Rev Neurosci 8:355–367
  • Umene-Nakano W, Yoshimura R, Ikenouchi-Sugita A et al (2009) Serum levels of brain-derived neurotrophic factor in comorbidity of depression and alcohol dependence. Hum Psychopharmacol 24:409–413. https://doi.org/10.1002/hup.1035
  • Vafadari B, Salamian A, Kaezmarek I (2016) MMP-9 in translation: from molecule to brain physiology, pathology and therapy. J Neurochem 139(Suppl 2):91–114
  • Vaynman S, Ying Z, Gomez-Pinilla F (2007) The select action of hippocampal calcium calmodulin protein kinase II in mediating exercise-enhanced cognitive function. Neuroscience 144:825–833. https://doi.org/10.1016/j.neuroscience.2006.10.005
  • Warnault V, Darcq E, Morisot N et al (2016) The BDNF valine 68 to methionine polymorphism increases compulsive alcohol drinking in mice that is reversed by tropomyosin receptor kinase B activation. Biol Psychiatry 79:463–473
  • Winnubst J, Cheyne JE, Niculescu D, Lohmann C (2015) Spontaneous activity drives local synaptic plasticity in vivo. Neuron 87(2):399–410. https://doi.org/10.1016/j.neuron.2015.06.029
  • Woo D, Seo Y, Jung H et al (2019) Locally activating TrKB receptor generates actin waves and specific axonal fate. Cell Chem Biol 26:1652–1663
  • Wrann CD, White JP, Salogiannnis J et al (2013) Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway. Cell Metab 18:649–659. https://doi.org/10.1016/j.cmet.2013.09.008
  • Xu B, Xie X (2016) Neurotrophic factor control of satiety and body weight. Nat Rev Neurosci 17:282–292. https://doi.org/10.1038/nrn.2016.24
  • Yamanaka M, Itakura Y, Inoue T et al (2006) Protective effect of brain-derived neurotrophic factor on pancreatic islets in obese diabetic mice. Metabolism 55:1286–1292. https://doi.org/10.1016/j.metabol.2006.04.017
  • Yamanaka M, Tsuchida A, Nakagawa T et al (2007) Brain-derived neurotrophic factor enhances glucose utilization in peripheral tissues of diabetic mice. Diabetes Obes Metab 9:59–64. https://doi.org/10.1111/j.1463-1326.2006.00572.x
  • Yang J, Siao CJ, Nagappan G et al (2009) Neuronal release of proBDNF. Nat Neurosci 12:113–115
  • Zhang JC, Yao W, Hashimoto K (2016) Brain-derived neurotrophic factor (BDNF)-TrkB signaling in inflammation-related depression and potential therapeutic targets. Curr Neuropharmacol 14:721–731. https://doi.org/10.2174/1570159x14666160119094646
  • Zuccato C, Cattaneo E (2009) Brain-derived neurotrophic factor in neurodegenerative diseases. Nat Rev Neurol 5(6):311–322. https://doi.org/10.1038/nrneurol.2009.54