Maternal alcohol binge drinking induces persistent neuroinflammation associated with myelin damage and behavioural dysfunctions in offspring mice

Cantacorps, Lídia; Alfonso-Loeches, Silvia; Moscoso-Castro, María; Cuitavi, Javier; Gracia-Rubio, Irene; López-Arnau, Raúl; Escubedo, Elena; Guerri, Consuelo; Valverde, Olga

doi:10.1016/j.neuropharm.2017.05.034

Cited by 51 publications

(81 citation statements)

References 97 publications

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“…Analysis of maternal body weight (Figure c) revealed a significant effect of time , but no significant effect of alcohol exposure. Thus, in agreement with previous studies (Cantacorps et al, ; Wilcox et al, ), our results show that alcohol consumption during the DID procedure does not affect maternal body weight.…”

Section: Resultssupporting

confidence: 94%

“…As previously reported (Cantacorps et al, 2017), blood alcohol concentration for dams reached levels of~0.8 gÁL −1 after the last binge drinking session (4-hr access) of the gestation and lactation periods.…”

Section: Did Testsupporting

confidence: 83%

“…This procedure was conducted as previously reported (Cantacorps et al, , ) to model a binge pattern of alcohol drinking, which is defined as the consumption of four or five alcoholic drinks (in women or men, respectively) on a single occasion, resulting in blood alcohol concentrations greater than 0.8 g·L −1 (NIAAA, ). Two days after mating, pregnant female mice were randomly assigned to two groups: alcohol and water exposed (control).…”

Section: Methodsmentioning

confidence: 99%

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Prenatal and postnatal alcohol exposure increases vulnerability to cocaine addiction in adult mice

Cantacorps

Montagud‐Romero

Luján

et al. 2020

British J Pharmacology

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Background and Purpose Alcohol exposure in utero may lead to a wide range of long‐lasting morphological and behavioural deficiencies known as fetal alcohol spectrum disorders (FASD), associated with a higher risk of later developing neuropsychiatric disorders. However, little is known about the long‐term consequences of cocaine use and abuse in individuals with FASD. This study aimed to investigate the effects of maternal binge alcohol drinking during prenatal and postnatal periods on cocaine reward‐related behaviours in adult offspring. Experimental Approach Pregnant C57BL/6 female mice were exposed to an experimental protocol of binge alcohol consumption (drinking‐in‐the‐dark test) from gestation to weaning. Male offspring were subsequently left undisturbed until reaching adulthood and were tested for cocaine‐induced motivational responses (conditioned place preference, behavioural sensitization and operant self‐administration). Protein expression of dopamine‐ and glutamate‐related molecules was assessed following cocaine‐induced reinstatement. Key Results The results show that prenatal and postnatal alcohol exposure enhanced the preference for the cocaine‐paired chamber in the conditioned place preference test. Furthermore, early alcohol‐exposed mice displayed attenuated cocaine‐induced behavioural sensitization but also higher cocaine self‐administration. Furthermore, alterations in glutamatergic excitability (GluA1/GluA2 ratio) and ΔFosB expression were found in the prefrontal cortex and the striatum of alcohol‐exposed mice after cocaine‐primed reinstatement. Conclusion and Implications Our findings demonstrate that maternal binge‐like alcohol consumption during gestation and lactation alters sensitivity to the reinforcing effects of cocaine in adult offspring mice. Together, such data suggest that prenatal and postnatal alcohol exposure may underlie an enhanced susceptibility of alcohol‐exposed offspring to develop drug addiction later in adulthood.

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Section: Resultssupporting

confidence: 94%

Section: Did Testsupporting

confidence: 83%

Section: Methodsmentioning

confidence: 99%

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Prenatal and postnatal alcohol exposure increases vulnerability to cocaine addiction in adult mice

Cantacorps

Montagud‐Romero

Luján

et al. 2020

British J Pharmacology

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“…In our recent study (Cantacorps et al, 2017), we reported spatial memory deficits and motor coordination impairments in a mouse model of FASD. Furthermore, with a view to elucidate the underlying molecular mechanisms in neurobehavioural phenotypes, we showed that maternal binge-like alcohol drinking during gestation and lactation periods produces an upregulation of proinflammatory signalling and myelination defects in the prefrontal cortex and hippocampus of adult offspring mice.…”

Section: Introductionmentioning

confidence: 90%

Altered brain functional connectivity and behaviour in a mouse model of maternal alcohol binge-drinking

Cantacorps

González-Pardo

Árias

et al. 2018

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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Prenatal and perinatal alcohol exposure caused by maternal alcohol intake during gestation and lactation periods can have long-lasting detrimental effects on the brain development and behaviour of offspring. Children diagnosed with Foetal Alcohol Spectrum Disorders (FASD) display a wide range of cognitive, emotional and motor deficits, together with characteristic morphological abnormalities. Maternal alcohol binge drinking is particularly harmful for foetal and early postnatal brain development, as it involves exposure to high levels of alcohol over short periods of time. However, little is known about the long-term effects of maternal alcohol binge drinking on brain function and behaviour. To address this issue, we used pregnant C57BL/6 female mice with time-limited access to a 20% v/v alcohol solution as a procedure to model alcohol binge drinking during gestation and lactational periods. Male offspring were behaviourally tested during adolescence (30 days) and adulthood (60 days), and baseline neural metabolic capacity of brain regions sensitive to alcohol effects were also evaluated in adult animals from both groups. Our results show that prenatal and postnatal alcohol exposure caused age-dependent changes in spontaneous locomotor activity, increased anxiety-like behaviour and attenuated alcohol-induced conditioned place preference in adults. Also, significant changes in neural metabolic capacity using cytochrome c oxidase (CCO) quantitative histochemistry were found in the hippocampal dentate gyrus, the mammillary bodies, the ventral tegmental area, the lateral habenula and the central lobules of the cerebellum in adult mice with prenatal and postnatal alcohol exposure. In addition, the analysis of interregional CCO activity correlations in alcohol-exposed adult mice showed disrupted functional brain connectivity involving the limbic, brainstem, and cerebellar regions. Finally, increased neurogenesis was found in the dentate gyrus of the hippocampus of alcohol-exposed offspring, suggesting neuroadaptive effects due to early alcohol exposure. Our results demonstrate that maternal binge-like alcohol drinking causes long-lasting effects on motor and emotional-related behaviours associated with impaired neuronal metabolic capacity and altered functional brain connectivity.

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“…When TLR4 receptors are blocked by T5342126, this effect is blunted, and voluntary EtOH consumption is reduced as well . Recent studies suggested that maternal binge‐like alcohol consumption induces neuroinflammation (upregulation of TLR4 and nuclear factor κB) and myelin damage in the brains of offspring and that such effects may underlie the persistent cognitive and behavioral impairments observed in FASDs . It was further shown that nalmefene, an opioid antagonist, prevents neuroinflammation and brain damage by blocking the TLR4 response and support the role of central proinflammatory immune signaling in the modulation of alcohol addiction .…”

Section: Etoh Can Indirectly Impact Myelin Through Its Microenvironmentmentioning

confidence: 99%

Function and Mechanism of Myelin Regulation in Alcohol Abuse and Alcoholism

Rice

2019

BioEssays

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Excessive alcohol use has adverse effects on the central nervous system (CNS) and can lead to alcohol use disorders (AUDs). Recent studies have suggested that myelin reductions may directly contribute to CNS dysfunctions associated with AUDs. Myelin consists of compact lipid membranes wrapped around axons to provide electrical insulation and trophic support. Regulation of myelin is considered as a new form of neural plasticity due to its profound impacts on the computation of neural networks. In this review, the authors first discuss experimental evidence showing how alcohol exposure causes demyelination in different brain regions, often accompanied by deficits in cognition and emotion. Next, they discuss postulated molecular and cellular mechanisms underlying alcohol's impact on myelin. It is clear that more extensive investigations are needed in this important but underexplored research field in order to gain a better understanding of the myelin-behavior relationship and to develop new treatment strategies for AUDs.

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Maternal alcohol binge drinking induces persistent neuroinflammation associated with myelin damage and behavioural dysfunctions in offspring mice

Cited by 51 publications

References 97 publications

Prenatal and postnatal alcohol exposure increases vulnerability to cocaine addiction in adult mice

Prenatal and postnatal alcohol exposure increases vulnerability to cocaine addiction in adult mice

Altered brain functional connectivity and behaviour in a mouse model of maternal alcohol binge-drinking

Function and Mechanism of Myelin Regulation in Alcohol Abuse and Alcoholism

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