medigraphic.com
ISSN 0185-3325 (Print)
Órgano Oficial del Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz

2015, Number 3

<< Back Next >>

Salud Mental 2015; 38 (3)

¿La exposición crónica al alcohol induce neurodegeneración en el Sistema Nervioso Central de la rata?

Hernández-Fonseca K, Martinell P, Reyes-Guzmán C, Méndez M

Language: Spanish
References: 58
Page: 167-176
PDF size: 842.45 Kb.


ABSTRACT

Background Chronic alcohol exposure is associated to neurotoxic and neurodegenerative mechanisms that lead to several cognitive and memory dysfunctions. Alcohol-induced damage depends on ethanol consumption patterns. Prolonged alcohol exposure induces damage in distinct brain regions (prefrontal, perirhinal, entorhinal and parahippocampal cortices, thalamus, hypothalamus, hippocampus and cerebellum) in both alcoholic patients and animal models of alcoholism. However, brain areas of the drug reinforcement and reward circuit have not been investigated.
Objective To investigate if chronic alcohol exposure induces neurodegenerative damage in the rat brain, particularly in the mesocorticolimbic system and the amygdala.
Method Male Wistar rats were exposed to ethanol (10% v/v) or water by oral consumption during 30 days. In another set of experiments, animals similarly treated with ethanol were withdrawn from the drug for 24 and 48 h. At the end of the treatments, animals were sacrificed, whole blood samples were obtained and the brains were removed. A fluorescence marker (Fluoro-Jade B) was used to assess neurodegenerative damage in the brain. Blood alcohol concentration was evaluated by spectrophotometry.
Results We observed a low number of Fluoro-Jade B positive cells in different brain regions, including the piriform cortex, frontal cortex of association, caudate-putamen and dorsal thalamus. No differences were found between chronic alcohol or ethanol withdrawn groups versus control animals.
Discussion and conclusion Our results suggest that chronic alcohol exposure does not induce neurodegeneration under the present experimental conditions. Alcohol blood concentrations attained during treatment may not be sufficient to induce cell death.


REFERENCES

  1. Organización Mundial de la Salud (OMS). Nota descriptiva N°349. Nueva York: febrero de 2011.

  2. González Guzmán R, Alcalá Ramírez J. Consumo de alcohol y salud pública. México: UNAM; 2005.

  3. Instituto Nacional de Psiquiatría, Dirección General de Epidemiología, Secretaría de Salud. Encuesta Nacional de Adicciones. Alcohol. México: 2008; pp.59-64.

  4. Medina-Mora ME, Natera G, Borges G. Alcoholismo y abuso de bebidas alcohólicas. En: Observatorio mexicano de tabaco, alcohol y otras drogas 2002. México: CONADIC, SSA; 2002.

  5. Koob GF, Volkow ND. Neurocircuitry of addiction. Neuropsychopharmacology 2009;35:217–238.

  6. Roberts AJ, Koob GF. The neurobiology of addiction: An overview. En: Neuroscience: Pathways of addiction. Alc Res Hlth 1997;21:101-106.

  7. Koob GF. Drug reward and addiction. En: Zigmond M, Bloom FE, Landis SC, Roberts JL, Squire LR (eds.). Fundamental neuroscience. San Diego: Academic Press;1999.

  8. Alcaro A, Huber R, Panksepp J. Behavioral functions of the mesolimbic dopaminergic system: an Affective neuroethological perspective. Brain Res Rev 2007;56:283–321.

  9. Björklund A, Dunnett SB. Dopamine neuron systems in the brain: an update. Trends Neurosci 2007;30:194-202.

  10. Grammatopoulos TN, Jones SM, Yoshimura M, Hoover BR et al. Neurotransplantation of stem cells genetically modified to express human dopamine transporter reduces alcohol consumption. Stem Cell Res Therp 2010;1:36.

  11. Méndez M, Herrera S. Behavioral effects of alcohol in rodents. En: Cruz-Morales SE, Arriaga-Ramírez P (eds.). Behavioral animal models. Fort PO Kerala, India: Research Signpost; 2012; 37;661.

  12. Sullivan E, Pfefferbaum A. Neurocircuitry in alcoholism: a substrate of disruption and repair. Psychopharmacology 2005;180:583–594.

  13. Bühler M, Mann K. Alcohol and the human brain: a systematic review of different neuroimaging methods. Alcohol Clin Exp Res 2011;35:1771-1793.

  14. Bowden SC, Crews FT, Bates ME, Fals-Stewart W et al. Neurotoxicity and neurocognitive impairments with alcohol and drug-use disorders: potential roles in addiction and recovery. Alcohol Clin Exp Res 2001;25:317-321.

  15. Pfefferbaum A, Sullivan EV, Mathalon DH, Lim KO. Frontal lobe volume loss observed with magnetic resonance imaging in older chronic alcoholics. Alcohol Clin Exp Res 1997;21:521–529.

  16. Matsumoto H, Matsumoto I. Alcoholism: protein expression profiles in a human hippocampal model. Expert Rev Proteomics 2008;5:321-331.

  17. Harper C. The neuropathology of alcohol-related brain damage. Alcohol Alcsm 2009;44:136-140.

  18. Fadda F, Rossetti ZL. Chronic ethanol consumption: From neuroadaptation to neurodegeneration. Prog Neurobiol 1998;56:385-431.

  19. Rosenbloom MJ, Rohlfing T, O’Reilly AW, Sassoon SA et al. Improvement in memory and static balance with abstinence in alcoholic men and women: Selective relations with change in brain structure. Psychiat Res 2007;155:91–102.

  20. Brust JC. Ethanol and cognition: indirect effects, neurotoxicity and neuroprotection: a review. Int J Environ Res Public Health 2010;7:1540- 1557.

  21. Bielawski D, Abel E. The effect of administering ethanol as single vs. divided doses on blood alcohol levels in the rat. Neurotoxicol Teratol 2002;24:559–562.

  22. Zou JY, Martinez DB, Neafsey, EJ, Collins MA. Binge ethanol-induced brain damage in rats: effect of inhibitors of nitric oxide synthase. Alcohol Clin Exp Res 1996;20:1406-1411.

  23. Obernier JA, Bouldin TW, Crews FT. Binge ethanol exposure in adult rats causes necrotic cell death. Alcohol Clin Exp Res 2002;26:547-557.

  24. Cippitelli A, Damadzic R, Frankola K, Goldstein A et al. Alcohol-induced neurodegeneration, suppression of transforming growth factor-beta, and cognitive impairment in rats: Prevention by group II metabotropic glutamate receptor activation. Biol Psychiatry 2010;67:823–830.

  25. Phillips SC, Cragg BG. Chronic consumption of alcohol by adult mice: effect on hippocampal cells and synapses. Exp Neurol 1983;80:218-226.

  26. Arendt T, Henning D, Gray JA, Marchbanks R. Loss of neurons in the rat basal forebrain cholinergic projection system after prolonged intake of ethanol. Brain Res Bul 1988;21:563-569.

  27. Zahr NM, Mayer D, Rohlfing T, Hasak M et al. Brain injury and recovery following binge ethanol: evidence from in vivo magnetic resonance spectroscopy. Biol Psychiatry 2009;67:846-854.

  28. Zahr NM, Kaufman KL, Harper CG. Clinical and pathological features of alcohol-related brain damage. Nature Reviews Neurology 2011;7:284-294.

  29. Lundqvist C, Alling C, Knoth R, Volk B. Intermittent ethanol exposure of adult rats: hippocampal cell loss after one month of treatment. Alcohol Alcsm 1995;30:737-748.

  30. Collins MA, Zou J, Neafsey EJ. Brain damage due to episodic alcohol exposure in vivo and in vitro: furosemide neuroprotection implicates edema-based mechanism. The FASEB Journal 1998;12:221-230.

  31. Crews FT, Braun CJ, Hoplight B, Switzer III RC et al. Binge ethanol consumption causes differential brain damage in young adolescent rats compared with adult rats. Alcohol Clin Exp Res 2000;24:1712-1723.

  32. Herrera DG, Yague AG, Johnsen-Soriano S, Bosch-Morell F et al. Selective impairment of hippocampal neurogenesis by chronic alcoholism: protective effects of an antioxidant. Proc Natl Acad Sci USA 2003;100:7919–7924.

  33. Paxinos G, Watson C. The rat brain in stereotaxic coordinates. 5th ed. San Diego, CA: Elsevier Academic Press; 2005.

  34. Chemicon, Fluoro-Jade B. Degenerating neurons. Billerica, MA: EMD Millipore Corporation; 2013.

  35. Invitrogen DAPI Nucleic Acid Stain. Eugene, OR: Molecular Probes Inc.; 2006.

  36. Poklis A, Mackell MA. Evaluation of a modified alcohol dehydrogenase assay for the determination of ethanol in blood. Clin Chem 1982;28:2125-2127.

  37. U.S. Department of Health and Human Services. National Institute on Alcohol Abuse and Alcoholism. En: Alcohol Research & Health. Highlights from the tenth special report to congress, health risks and benefits of alcohol consumption (ed.). Washington, DC: Government Printing Office; 2000; vol.24, No. 1.

  38. Collins MA, Corso TD, Neafsey EJ. Neuronal degeneration in rat cerebrocortical and olfactory regions during subchronic binge intoxication with ethanol: possible explanation for olfactory deficits in alcoholics. Alcohol Clin Exp Res 1996;20:284-292.

  39. Switzer III RC. Application of silver degeneration stains for neurotoxicity testing. Toxicol Pathol 2000;28:70–83.

  40. Crews FT, Collins MA, Dlugos C, Littleton J et al. Alcohol-induced neurodegeneration: when, where and why? Alcohol Clin Exp Res 2004;28:350-364.

  41. Pfefferbaum A, Sullivan EV, Mathalon DH, Shear PK et al. Longitudinal changes in magnetic resonance imaging brain volumes in abstinent and relapsed alcoholics. Alcohol Clin Exp Res 1995;19:1177-1191.

  42. Nixon K, Crews FT. Binge alcohol exposure decreases neurogenesis in adult rat hippocampus. J Neurochem 2002;83:1087–1093.

  43. Leriche M, Méndez M. Ethanol exposure selectively alters beta-endorphin content but not [3H]-DAMGO binding in discrete regions of the rat brain. Neuropeptides 2010;44:9-16.

  44. Faingold CL. The majchrowicz binge alcohol protocol: An intubation technique to study alcohol dependence in rats. Curr Protoc Neurosci 2008;9:

  45. Kishimoto R, Fujiwara I, Kitayama S, Goda K et al. Changes in hepatic enzyme activities related to ethanol metabolism in mice following chronic ethanol administration. J Nutr Sci Vitaminol (Tokyo) 1995;41:527-543.

  46. Lieber CS. Cytochrome P450 2E1: its physiological and pathological role. Physiol Rev 1997;77:517-544.

  47. Lieber CS. Microsomal ethanol-oxidizing system (MEOS): the first 30 years (1968-1998)a review. Alcohol Clin Exp Res 1999;23:991-1007.

  48. Zimatkin SM, Pronko SP, Vasiliou V, Gonzalez FJ et al. Enzymatic mechanisms of ethanol oxidation in the brain. Alcohol Clin Exp Res 2006;30:1500-1505.

  49. Zakhari S. Overview: How is alcohol metabolized by the body? Alc Res Hlth 2007;29:245-254.

  50. Haseba T, Ohno Y. A new view of alcohol metabolism and alcoholism-- role of the high-Km Class III alcohol dehydrogenase (ADH3). Int J Environ Res Public Health 2010;7:1076-1092.

  51. Salaspuro MP, Lieber CS. Non-uniformity of blood ethanol elimination: its exaggeration after chronic consumption. Ann Clin Res 1978;10:294-297.

  52. Pikkarainen PH, Lieber CS. Concentration dependency of ethanol elimination rates in baboons: effect of chronic alcohol consumption. Alcohol Clin Exp Res 1980;4:40-43.

  53. Dikranian K, Ishimaru MJ, Tenkova T, Labruyere J et al. Apoptosis in the in vivo Mammalian Forebrain. Neurobiol Dis 2001;8:359-379.

  54. Cordeiro MF, Guo L, Luong V, Harding G et al. Real-time imaging of single nerve cell apoptosis in retinal neurodegeneration. PNAS 2004;101:13352-13356.

  55. Cordeiro MF, Luong V, Maass A, Guo L et al. Time–course of single cell apoptosis in vivo using video and image analysis of retinal ganglion cell disease model. Invest Ophthalmol Vis Sci 2005;46:4823-4826.

  56. Okamoto K, Mizuno M, Nakahara N, Natsume A et al. Process of apoptosis induced by TNF-α in murine fibroblast Ltk-cells: Continuous observation with video enhanced contrast microscopy. Apoptosis 2002;7:77–86.

  57. Rudolf E, Peychl J, Cervinka M. The dynamics of the hexavalent chromium induced apoptotic patterns in vitro. Acta Medica 2000;43:83-89.

  58. Lipton P. Ischemic cell death in brain neurons. Physiol Rev 1999;79:1431-1568.




2020     |     www.medigraphic.com