Cerebellar and cortical TLR4 activation and behavioral impairments in Wernicke-Korsakoff Syndrome: Pharmacological effects of oleoylethanolamide

Moya, Marta; Felipe, Diego San; Ballesta, Antonio; Alén, Francisco; Fonseca, Fernando Rodrı́guez de; García‐Bueno, Borja; Marco, Eva M.; Orío, Laura

doi:10.1016/j.pnpbp.2020.110190

Cited by 16 publications

(45 citation statements)

References 74 publications

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“…The frontal cortex is a structure vulnerable to damage by both alcohol and TD, as it has been described in previous studies (reviewed in [16]), including some of our research group [17,18].…”

Section: Introductionmentioning

confidence: 70%

“…Since the beginning of the study, rats of TDD group (n = 9) had access to a single bottle with tap water and were fed with the standard food, but the last 12 days of the experiment, the chow was replaced by a thiamine-deficient diet (residual thiamine level in diet <0.5 ppm; Teklad Custom Diet, Envigo, Madison,WI, USA), in conjunction with daily pyrithiamine hydrobromide (thiamine pyrophosphokinase inhibitor) injections (Sigma Aldrich, Madrid, Spain; 0.25 mg/kg; i.p.) (WKS Pre-Symptomatic Model (PSM) protocol in [18]).…”

Section: • Td Diet (Tdd)mentioning

confidence: 99%

“…We focused on the evaluation of motor and cognitive domains, as we did in previous studies of WKS [18]. The time-course of behavioral assessments, appropriately scheduled not to interfere between them, is depicted in Figure 1.…”

Section: Behavioral Assessmentmentioning

confidence: 99%

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Disinhibited-Like Behavior Correlates With Frontal Cortex Damage in Alcohol-Induced Wernicke-Korsakoff Syndrome

Moya¹,

López-Valencia²,

García‐Bueno³

et al. 2021

Preprint

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Wernicke-Korsakoff syndrome (WKS) is induced by thiamine deficiency (TD) and mainly related to alcohol consumption. Frontal cortex dysfunction has been associated to impulsivity and disinhibition in WKS patients. The pathophysiology involves oxidative stress, excitotoxicity and inflammatory responses leading to neuronal death, but the relative contributions of each factor (alcohol and TD, isolate or in interaction) to these phenomena are still poorly understood. A rat model was used by forced consumption of 20% (w/v) alcohol for 9 months (CA), TD hit (TD diet + pyrithiamine 0.25 mg/kg, i.p. daily injections the last 12 days of experimentation; TDD), and both combined treatments (CA+TDD). Motor and cognitive performance and cortical damage were examined. CA caused hyperlocomotion as a possible sensitization of ethanol-induced excitatory effects and recognition memory deficits. In addition, CA+TDD animals showed a disinhibited-like behavior, which appears to be dependent on TDD. Also, combined treatment led to more pronounced alterations in nitrosative stress, lipid peroxidation, apoptosis and cell damage markers. Correlations between injury signals and disinhibition suggest that CA+TDD disrupts behaviors dependent on the frontal cortex. Our study sheds light on the potential disease-specific mechanisms, reinforcing the need for neuroprotective therapeutic approaches along with preventive treatments for the nutritional deficiency in WKS.

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Section: Introductionmentioning

confidence: 70%

Section: • Td Diet (Tdd)mentioning

confidence: 99%

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Disinhibited-Like Behavior Correlates With Frontal Cortex Damage in Alcohol-Induced Wernicke-Korsakoff Syndrome

Moya¹,

López-Valencia²,

García‐Bueno³

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

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“…Indivíduos assim, frequentemente apresentam danos cerebrais como consequência tanto da DT quanto pela neurotoxicidade induzida pelo álcool. As principais alterações patológicas com a DT em humanos, envolve o sistema nervoso e cardiovascular (MOYA, et al 2020).…”

Section: Discussionunclassified

Impacto Do Transtorno Do Estresse Pós-Traumático Por Abuso Sexual No Desenvolvimento Cerebral Infantil

Leite¹,

Farias²,

Rainho³

et al. 2021

Ciências Médicas: Campo Teórico, Métodos, Aplicabilidade E Limitações 2

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Direitos para esta edição cedidos à Atena Editora pelos autores. Open access publication by Atena Editora Todo o conteúdo deste livro está licenciado sob uma Licença de Atribuição Creative Commons. Atribuição-Não-Comercial-NãoDerivativos 4.0 Internacional (CC BY-NC-ND 4.0).O conteúdo dos artigos e seus dados em sua forma, correção e confiabilidade são de responsabilidade exclusiva dos autores, inclusive não representam necessariamente a posição oficial da Atena Editora. Permitido o download da obra e o compartilhamento desde que sejam atribuídos créditos aos autores, mas sem a possibilidade de alterá-la de nenhuma forma ou utilizá-la para fins comerciais. Todos os manuscritos foram previamente submetidos à avaliação cega pelos pares, membros do Conselho Editorial desta Editora, tendo sido aprovados para a publicação com base em critérios de neutralidade e imparcialidade acadêmica.A Atena Editora é comprometida em garantir a integridade editorial em todas as etapas do processo de publicação, evitando plágio, dados ou resultados fraudulentos e impedindo que interesses financeiros comprometam os padrões éticos da publicação. Situações suspeitas de má conduta científica serão investigadas sob o mais alto padrão de rigor acadêmico e ético.

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“…OEA and PEA attenuated TLR4-induced NFκB activity, IL-1β, COX-2, mPGES-1 expression and PGE2 levels in the hypothalamus, an effect associated with potentiation of TLR4-induced hypothermia ( Sayd et al, 2015 ). OEA blocks the TLR4-mediated increases in pro-inflammatory cytokines and chemokines, oxidative and nitrosative stress, and neurodegenerative cascades in frontal cortex of a rodent model of alcohol abuse ( Orio et al, 2018 ; Rivera et al, 2019 ) and neuropsychiatric conditions ( Moya et al, 2021 ). Collectively, this demonstrates that AEA, OEA and PEA modulate TLR4-induced inflammatory responses; however, there is a paucity of studies investigating the effects of individual N -acylethanolamines on TLR3-induced inflammatory responses.…”

Section: Introductionmentioning

confidence: 99%

N-acylethanolamine regulation of TLR3-induced hyperthermia and neuroinflammatory gene expression: A role for PPARα

Flannery

Kerr

Hughes

et al. 2021

Journal of Neuroimmunology

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Increasing evidence suggests that SARS-CoV-2, the virus responsible for the COVID-19 pandemic, is associated with increased risk of developing neurological or psychiatric conditions such as depression, anxiety or dementia. While the precise mechanism underlying this association is unknown, aberrant activation of toll-like receptor (TLR)3, a viral recognizing pattern recognition receptor, may play a key role. Synthetic cannabinoids and enhancing cannabinoid tone via inhibition of fatty acid amide hydrolase (FAAH) has been demonstrated to modulate TLR3-induced neuroimmune responses and associated sickness behaviour. However, the role of individual FAAH substrates, and the receptor mechanisms mediating these effects, are unknown. The present study examined the effects of intracerebral or systemic administration of the FAAH substrates N -oleoylethanolamide (OEA), N -palmitoylethanolamide (PEA) or the anandamide (AEA) analogue meth-AEA on hyperthermia and hypothalamic inflammatory gene expression following administration of the TLR3 agonist, and viral mimetic, poly I:C. The data demonstrate that meth-AEA does not alter TLR3-induced hyperthermia or hypothalamic inflammatory gene expression. In comparison, OEA and PEA attenuated the TLR3-induced hyperthermia, although only OEA attenuated the expression of hyperthermia-related genes ( IL-1β, iNOS, COX2 and m-PGES ) in the hypothalamus. OEA, but not PEA, attenuated TLR3-induced increases in the expression of all IRF- and NFκB-related genes examined in the hypothalamus, but not in the spleen. Antagonism of PPARα prevented the OEA-induced attenuation of IRF- and NFκB-related genes in the hypothalamus following TLR3 activation but did not significantly alter temperature. PPARα agonism did not alter TLR3-induced hyperthermia or hypothalamic inflammatory gene expression. These data indicate that OEA may be the primary FAAH substrate that modulates TLR3-induced neuroinflammation and hyperthermia, effects partially mediated by PPARα.

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Cerebellar and cortical TLR4 activation and behavioral impairments in Wernicke-Korsakoff Syndrome: Pharmacological effects of oleoylethanolamide

Cited by 16 publications

References 74 publications

Disinhibited-Like Behavior Correlates With Frontal Cortex Damage in Alcohol-Induced Wernicke-Korsakoff Syndrome

Disinhibited-Like Behavior Correlates With Frontal Cortex Damage in Alcohol-Induced Wernicke-Korsakoff Syndrome

Impacto Do Transtorno Do Estresse Pós-Traumático Por Abuso Sexual No Desenvolvimento Cerebral Infantil

N-acylethanolamine regulation of TLR3-induced hyperthermia and neuroinflammatory gene expression: A role for PPARα

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