Alterations in Neurotrophins in Alcohol-Addicted Patients During Alcohol Withdrawal

Overview

Journal Brain Sci

Publisher MDPI

Date 2024 Jun 27

PMID 38928583

Authors

Magda Malewska-Kasprzak

Maria Skibinska

Monika Dmitrzak-Weglarz

Affiliations

Soon will be listed here.

Abstract

Background: Alcohol use disorder (AUD) is related to mental and somatic disorders that result in alcohol withdrawal syndrome (AWS), with 30% of AWS cases leading to life-threatening delirium tremens (DTs). Currently, studies do not support using any one biomarker in DTs. Neurotrophins affect neuromodulation, playing a role in the pathogenesis of AUD, AWS, and DTs.

Methods: This review aims to summarize experimental and clinical data related to neurotrophins and S100B in neuroplasticity, as well as neurodegeneration in the context of AUD, AWS, and DTs. This work used publications that were selected based on the protocol consistent with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement.

Results: The BDNF level could be a good candidate biomarker for relapse susceptibility, as it is significantly reduced during consumption and gradually increases during abstinence. GDNF influences AUD through its integral role in the function of dopaminergic neurons and ablates the return to alcohol-drinking behavior. NGF protects neurons from ethanol-induced cytotoxic damage and affects recovery from cognitive deficits after brain damage. The NT-3 level is decreased after alcohol exposure and is involved in compensatory mechanisms for cognitive decline in AUD. NT-4 affects oxidative stress, which is associated with chronic alcohol consumption. S100B is used as a biomarker of brain damage, with elevated levels in serum in AUD, and can protect 5-HT neurons from the damage caused by alcohol.

Conclusions: BDNF, GDNF, NT-3, NT-4, NGF, and S100B may be valuable markers for withdrawal syndrome. In particular, the most relevant is their association with the development of delirium complications. However, there are few data concerning some neurotrophins in AWS and DTs, suggesting the need for further research.

References

Stoicea N, McVicker S, Quinones A, Agbenyefia P, Bergese S . Delirium-biomarkers and genetic variance. Front Pharmacol. 2014; 5:75. PMC: 3997036. DOI: 10.3389/fphar.2014.00075. View

Smith A, Ovesen P, Skeldal S, Yeo S, Jensen K, Olsen D . Risk Locus Identification Ties Alcohol Withdrawal Symptoms to SORCS2. Alcohol Clin Exp Res. 2018; 42(12):2337-2348. PMC: 6317871. DOI: 10.1111/acer.13890. View

Luis C, Pascual A . Simultaneous Detection of Both GDNF and GFRα1 Expression Patterns in the Mouse Central Nervous System. Front Neuroanat. 2016; 10:73. PMC: 4919337. DOI: 10.3389/fnana.2016.00073. View

Heberlein A, Buscher P, Schuster R, Kleimann A, Lichtinghagen R, Rhein M . Do changes in the BDNF promoter methylation indicate the risk of alcohol relapse?. Eur Neuropsychopharmacol. 2015; 25(11):1892-7. DOI: 10.1016/j.euroneuro.2015.08.018. View

ERIKSEN J, Druse M . Astrocyte-mediated trophic support of developing serotonin neurons: effects of ethanol, buspirone, and S100B. Brain Res Dev Brain Res. 2001; 131(1-2):9-15. DOI: 10.1016/s0165-3806(01)00240-1. View

Girard M, Malauzat D, Nubukpo P . Serum inflammatory molecules and markers of neuronal damage in alcohol-dependent subjects after withdrawal. World J Biol Psychiatry. 2017; 20(1):76-90. DOI: 10.1080/15622975.2017.1349338. View

Umene-Nakano W, Yoshimura R, Ikenouchi-Sugita A, Hori H, Hayashi K, Ueda N . Serum levels of brain-derived neurotrophic factor in comorbidity of depression and alcohol dependence. Hum Psychopharmacol. 2009; 24(5):409-13. DOI: 10.1002/hup.1035. View

Girard M, Carrier P, Loustaud-Ratti V, Nubukpo P . BDNF levels and liver stiffness in subjects with alcohol use disorder: Evaluation after alcohol withdrawal. Am J Drug Alcohol Abuse. 2020; 47(2):191-198. DOI: 10.1080/00952990.2020.1833211. View

Grondin R, Meagan Littrell O, Zhang Z, Ai Y, Huettl P, Pomerleau F . GDNF revisited: A novel mammalian cell-derived variant form of GDNF increases dopamine turnover and improves brain biodistribution. Neuropharmacology. 2018; 147:28-36. DOI: 10.1016/j.neuropharm.2018.05.014. View

10.

Vaht M, Laas K, Kiive E, Parik J, Veidebaum T, Harro J . A functional neuregulin-1 gene variant and stressful life events: Effect on drug use in a longitudinal population-representative cohort study. J Psychopharmacol. 2016; 31(1):54-61. DOI: 10.1177/0269881116655979. View

11.

Liran M, Rahamim N, Ron D, Barak S . Growth Factors and Alcohol Use Disorder. Cold Spring Harb Perspect Med. 2020; 10(12). PMC: 7371553. DOI: 10.1101/cshperspect.a039271. View

12.

Heaton M, Moore D, Paiva M, Madorsky I, Mayer J, Shaw G . The role of neurotrophic factors, apoptosis-related proteins, and endogenous antioxidants in the differential temporal vulnerability of neonatal cerebellum to ethanol. Alcohol Clin Exp Res. 2003; 27(4):657-69. DOI: 10.1097/01.ALC.0000060527.55252.71. View

13.

Martin-Gonzalez C, Romero-Acevedo L, Fernandez-Rodriguez C, Medina-Vega L, Garcia-Rodriguez A, Ortega-Toledo P . Brain-derived neurotrophic factor among patients with alcoholism. CNS Spectr. 2020; 26(4):400-405. DOI: 10.1017/S1092852920001431. View

14.

Wang R, Li Y, Xu Y, Li Y, Wu H, Guo H . Curcumin produces neuroprotective effects via activating brain-derived neurotrophic factor/TrkB-dependent MAPK and PI-3K cascades in rodent cortical neurons. Prog Neuropsychopharmacol Biol Psychiatry. 2009; 34(1):147-53. DOI: 10.1016/j.pnpbp.2009.10.016. View

15.

Sery O, Stastny F, Zvolsky P, Hlinomazova Z, Balcar V . Association between Val66Met polymorphism of Brain-Derived Neurotrophic Factor (BDNF) gene and a deficiency of colour vision in alcohol-dependent male patients. Neurosci Lett. 2011; 499(3):154-7. DOI: 10.1016/j.neulet.2011.05.038. View

16.

Lhullier A, Moreira F, da Silva R, Marques M, Bittencourt G, Pinheiro R . Increased serum neurotrophin levels related to alcohol use disorder in a young population sample. Alcohol Clin Exp Res. 2015; 39(1):30-3. DOI: 10.1111/acer.12592. View

17.

Wojnar M, Brower K, Strobbe S, Ilgen M, Matsumoto H, Nowosad I . Association between Val66Met brain-derived neurotrophic factor (BDNF) gene polymorphism and post-treatment relapse in alcohol dependence. Alcohol Clin Exp Res. 2009; 33(4):693-702. PMC: 2928673. DOI: 10.1111/j.1530-0277.2008.00886.x. View

18.

Enoch M, White K, Waheed J, Goldman D . Neurophysiological and genetic distinctions between pure and comorbid anxiety disorders. Depress Anxiety. 2007; 25(5):383-92. DOI: 10.1002/da.20378. View

19.

Jeon H, Kang E, Lee E, Jeong E, Jeon J, Mischoulon D . Childhood trauma and platelet brain-derived neurotrophic factor (BDNF) after a three month follow-up in patients with major depressive disorder. J Psychiatr Res. 2012; 46(7):966-72. DOI: 10.1016/j.jpsychires.2012.04.006. View

20.

Barbey A, Colom R, Paul E, Forbes C, Krueger F, Goldman D . Preservation of general intelligence following traumatic brain injury: contributions of the Met66 brain-derived neurotrophic factor. PLoS One. 2014; 9(2):e88733. PMC: 3935849. DOI: 10.1371/journal.pone.0088733. View