Thème : CERVEAU

Grisel J.J. et Chen W.J.

Antioxidant pretreatment does not ameliorate alcohol-induced Purkinje cell loss in the developing rat cerebellum

Alcoholism: Clinical and Experimental Research, RSA & ISBRA (Dir.) ; Lippincott Williams & Wilkins ; 2005, Vol.29, n°7, 1223-1229

Mots-Clefs : ANTIOXYDANT / CELLULE DE PURKINJE / CERVEAU / CERVELET / CONSOMMATION / MELATONINE / MODELE ANIMAL / NOUVEAU-NE / RAT / STRESS OXYDATIF

Dans cette étude, deux antioxydants connus, la melatonine et l'U83836E, ont été évalués pour leur efficacité de bloquant de la perte cérébelleuse alcool-induite des cellules de Purkinje chez les rats nouveau-nés. (Note Ireb).

Background: Recent research has suggested that oxidative stress is a potential mechanism for alcohol-induced injury and that supplementation with antioxidants can ameliorate alcohol-induced damage. In this study, two known antioxidants, melatonin and U83836E, were assessed for their effectiveness in blocking the expected alcohol-induced cerebellar Purkinje cell loss in neonatal rat pups.

Methods: Sprague-Dawley rat pups were artificially reared from postnatal days (PDs) 4-9 and were exposed to either alcohol or antioxidants (melatonin or U83836E) individually or in combination. A normal control group (raised by rat dams) was included in this study. On PD 9, the brain from each pup was removed and weighed, and the cerebellar vermis was processed for stereological cell counting.

Results: Alcohol exposure during the brain growth spurt produced microencephaly, in addition to significant decreases in the number and density of Purkinje cells in lobule I and the volume of lobule I. The antioxidants did not reduce any of the adverse effects observed from alcohol exposure, and they did not decrease the Purkinje cell number when administered alone. Furthermore, antioxidants did not change the only blood alcohol concentration measured on PD 6.

Conclusions: The results confirmed alcohol-induced microencephaly and cerebellar Purkinje cell loss from neonatal alcohol exposure, and they showed that either antioxidant could attenuate these adverse effects on the developing brain. The inability of antioxidants to reduce Purkinje cell loss from neonatal alcohol exposure suggests the existence of alternative mechanisms for developmental alcohol-induced Purkinje cell loss.

Source : Ireb, article - périodique, P0004, 21064

Thème : CERVEAU

Gazdzinski S., Durazzo T.C. et Meyerhoff D.J.

Temporal dynamics and determinants of whole brain tissue volume changes during recovery from alcohol dependence

Drug and Alcohol Dependence, 2005, Vol.78, n°3, 263-273

Mots-Clefs : ABSTINENCE / ALCOOLISME / CERVEAU / IRM / MODELE ANIMAL / RAT / RECHUTE

En utilisant l'imagerie par résonance magnétique, les chercheurs testent la possibilité d'une réversibilité des dommages cérébraux lors de l'abstinence chez des rats alcoolo-dépendants. (Note Ireb).

Brain shrinkage and its partial reversibility with abstinence is a common neuroimaging finding in alcohol dependent individuals. We used an automated three-dimensional whole brain magnetic resonance imaging method (boundary shift integral) in 23 alcohol dependent individuals to measure the temporal dynamics of cerebral tissue and spinal fluid volume changes over a 12-month interval and to examine the major determinants of brain tissue change rates during abstinence and non-abstinence. We found more rapid brain tissue gain during the first month of sobriety than in the following months. The most rapid volume recovery was observed in abstinent individuals with the greatest baseline brain shrinkage and drinking severity. The rapid reversal of brain volume gains in non-abstinent individuals and tissue volume changes are modulated by duration of abstinence and non-abstinence periods, as well as recency of non-abstinence. Age, family history density of alcoholism, relapse severity, and duration or age of onset of heavy drinking were not major determinants of brain shrinkage and brain volume recovery rates. Treatment providers may use this tangible information to reinforce the biomedical benefits of sobriety. Previous quantitative measurements of brain volumes in alcohol dependent individuals performed after several weeks of abstinence likely underestimated the full extent of chronic alcohol-associated brain shrinkage.

Source : Ireb, article - tiré à part, P0010, 21083

Thème : CERVEAU

Heilig M. et Thorsell A.

Brain neuropeptide Y (NPY) in stress and alcohol dependence

Reviews in the Neurosciences, 2002, Vol.13, n°1, 85-94

Mots-Clefs : ALCOOLISME / AMYGDALE / ANXIETE / NEUROPEPTIDE Y / STRESS

Les chercheurs décrivent l'implication du neuropeptide Y dans le stress et l'alcoolisme. (Note Ireb).

Neuropeptide Y (NPY), the prototypical member of the NPY-like peptide family, antagonizes behavioral consequences of stress through actions within the brain. This was initially indicated by microinjection studies with NPY receptor ligands, suggesting that NPY Y1 receptors mediate the anti-stress effects of NPY. Behavioral anti-stress actions of NPY are note-worthy in that 1) their magnitude surpasses that of other endogenous compounds; 2) they are produced across a wide range of animal models, normally thought to reflect different aspects of emotionality. These findings suggest that NPY acts with a high potency on a common core mechanism of emotionality and behavioral stress responses. This hypothesis is supported by behavioral studies in genetically modified animals. Increased emotionality, as well as increased alcohol intake, has been reported in mice with a homologous recombination knockout of the preproNPY gene. More detailed studies have been made possible by a transgenic rat system, in which NPY is selectively overexpressed within the hippocampus. These subjects display no overt phenotype under baseline conditions and have a normal endocrine stress response, but lack behavioral responses to stress. These findings point to the potential of the NPY system for developing novel pharmacological treatments of stress-related disorders, including anxiety and depression. Recent data additionally point to a role of NPY in the regulation of alcohol intake, and alcohol dependence emerges as a novel potential indication for compounds targeting the NPY system.

Source : Ireb, article - tiré à part, TAP 005 599, 21123

Thème : CERVEAU

Quertemont E., Eriksson C.J., Zimatkin S.M., Pronko P.S., Diana M., Pisano M., Rodd Z.A., Bell R.R. et Ward R.J.

Is ethanol a pro-drug? Acetaldehyde contribution to brain ethanol effects

Alcoholism: Clinical and Experimental Research, RSA & ISBRA (Dir.) ; Lippincott Williams & Wilkins ; 2005, Vol.29, n°8, 1514-1521

Mots-Clefs : ACETALDEHYDE / AUTO-ADMINISTRATION / CATALASE / CERVEAU / COLLOQUE / CONSOMMATION / DOPAMINE

Cet article résume l'ensemble des interventions faites au colloque de l'ISBRA, en octobre 2004, sur la contribution de l'acétaldéhyde aux effets de l'éthanol sur le cerveau. (Note Ireb).

This article presents the proceedings of a symposium at the 2004 meeting of the International Society for Biomedical Research on Alcoholism, held in Mannheim, Germany. The symposium was organized by Etienne Quertemont and chaired by C. J. Peter Eriksson. The presentations were (1) Brain ethanol metabolism and its behavior consequences, by Sergey M. Zimatkin and P. S. Pronko; (2) Acetaldehyde increases dopaminergic neuronal activity: a possible mechanism for acetaldehyde reinforcing effects, by Marco Diana and Milena Pisano; (3) Contrasting the reinforcing actions of acetaldehyde and ethanol within the ventral tegmental area (VTA) of alcohol-preferring (P) rats, by Zachary A. Rodd and Richard R. Bell; (4) Molecular and biochemical changes associated with acetaldehyde in human alcoholism and alcohol abuse, by C. J. Peter Eriksson.

Source : Ireb, article - périodique, P0004, 21168

Thème : CERVEAU

Jorge R.E., Starkstein S.E., Arndt S., Moser D., Crespo-Facorro B. et Robinson R.G.

Alcohol misuse and mood disorders following traumatic brain injury

Archives of General Psychiatry, 2005, Vol.62, n°7, 742-749

Mots-Clefs : CERVEAU / CONSOMMATION EXCESSIVE / ETUDE COMPARATIVE / ETUDE PROSPECTIVE / HUMEUR / TRAUMATISME

Les chercheurs comparent les résultats psychiatriques, neuropsychologiques et psychosociaux parmi des patients ayant subi des blessures traumatiques au cerveau avec ou sans un passif d'abus d'alcool et/ou de dépendance durant la première année après le trauma. Ils émettent l'hypothèse que la présence d'abus d'alcool et/ou de dépendance pourrait être significativement associée à des troubles de l'humeur. (Note Ireb).

Context: Alcohol abuse and/or dependence (AA/D) and mood disturbance are co-occurring conditions among patients who have had a traumatic brain injury (TBI). However, the relationship between these disorders has not been extensively studied.

Objective: To examine the relationship of AA/D and post-TBI mood disorders and the effect of these conditions on psychosocial outcome.

Design: Prospective, case-control surveillance study conducted during the first year following trauma.

Settings: University hospital level I trauma centers and specialized rehabilitation units.

Patients: One hundred fifty-eight TBI patients with closed head injury with and without a history of AA/D.

Methods: We prospectively compared psychiatric, neuropsychological, and psychosocial outcomes among the patients, who were evaluated at baseline and at 3, 6, and 12 months after trauma. Psychiatric diagnosis was made using a structured clinical interview and DSM-IV criteria. Neuropsychological testing results and quantitative magnetic resonance images were obtained at the 3-month follow-up.

Results: A history of AA/D was significantly more frequent among patients who developed mood disorders during the first year following TBI. There was also a significantly higher frequency of mood disorders among patients with alcohol abuse relapse. Patients with a history of AA/D had significantly reduced frontal gray matter volumes than did patients without a history of alcohol abuse. In addition, patients who resumed alcohol abuse had decreased medial frontal gray matter volumes and impaired performance in executive tasks. Both AA/D and mood disorders following TBI were associated with a poor vocational outcome.

Conclusions: Previous alcohol abuse increases the risk of developing mood disorders after TBI, and emotional disturbance, in turn, increases the risk of alcohol abuse relapse. Alcohol's neurotoxic effects and TBI likely interact to produce greater disruption of the neural circuits that modulate reward, mood, and executive function. Patients with a history of AA/D who also developed mood disorders following TBI had major difficulties resuming a productive life.

Source : Ireb, article - tiré à part, TAP 005 559, 21202