COVID-19-related cognitive dysfunction may be associated with transient disruption in the DLPFC glutamatergic pathway

Yeşilkaya, Ümit Haluk; Sen, Manodeep; Balcıoğlu, Yasin Hasan

doi:10.1016/j.jocn.2021.03.007

Cited by 23 publications

(30 citation statements)

References 13 publications

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“…Conversely, Magenetic Resonance Spectroscopy (MRS) for the analysis of glutamate, glutamine and N-acetyl aspartate clearly showed a reduction of these molecules in the dorso-lateral prefrontal cortex (DLPFC), which is corroborated by our findings. Interestingly, three months after infection, neurological impairment has stope as well as glutamate/glutamine levels were reestablished 44 . Thus, to our knowledge, this is the first report to demonstrate the impact of COVID-19 over the metabolic and proteomic profile of brain cells, specifically astrocytes.…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 Infection Impacts Carbon Metabolism and Depends on Glutamine for Replication in Syrian Hamster Astrocytes

Oliveira

Angelo

Yamamoto

et al. 2021

Preprint

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Coronaviruses belong to a well-known family of enveloped RNA viruses and are the causative agent of the common cold. Although the seasonal coronaviruses do not pose a threat to human life, three members of this family, i.e., SARS-CoV, MERS-CoV and recently, SARS-CoV2, may cause severe acute respiratory syndrome and lead to death. Unfortunately, COVID-19 has already caused more than 4.4 million deaths worldwide. Although much is better understood about the immunopathogenesis of the lung disease, important information about systemic disease is still missing, mainly concerning neurological parameters. In this context, we sought to evaluate immunometabolic changes using in vitro and in vivo models of hamsters infected with SARS-CoV-2. Here we show that, besides infecting hamsters astrocytes, SARS-CoV-2 induces changes in protein expression and metabolic pathways involved in carbon metabolism, glycolysis, mitochondrial respiration, and synaptic transmission. Interestingly, many of the differentially expressed proteins are concurrent with proteins that correlate with neurological diseases, such as Parkinsons's disease, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington's disease. Metabolic analysis by high resolution real-time respirometry evidenced hyperactivation of glycolysis and mitochondrial respiration. Further metabolomics analysis confirmed the consumption of many metabolites, including glucose, pyruvate, glutamine, and alpha ketoglutarate. Interestingly, we observed that glutamine was significantly reduced in infected cultures, and the blockade of mitochondrial glutaminolysis significantly reduced viral replication and pro-inflammatory response. SARS-CoV-2 was confirmed in vivo as hippocampus, cortex, and olfactory bulb of intranasally infected hamsters were positive for viral genome several days post-infection. Altogether, our data reveals important changes in overall protein expression, mostly of those related to carbon metabolism and energy generation, causing an imbalance in important metabolic molecules and neurotransmitters. This may suggest that some of the neurological features observed during COVID-19, as memory and cognitive impairment, may rely on altered energetic profile of brain cells, as well as an unbalanced glutamine/glutamate levels, whose importance for adequate brain function is unquestionable.

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Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 Infection Impacts Carbon Metabolism and Depends on Glutamine for Replication in Syrian Hamster Astrocytes

Oliveira

Angelo

Yamamoto

et al. 2021

Preprint

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“…Outra situação aventada refere-se ao neurotropismo viral e consequente neuroinflamação envolvidas na patogênese, como observado em alguns estudos 18,19 de tal modo que, ao se analisar mais profundamente, um grupo de pesquisadores 13 observou uma redução na atividade de neurotransmissão gabaérgica correlacionada ao distúrbio cognitivo, consequente à neuroinflamação. Em se tratando de neurotransmissor, um relato de caso sugere também que os déficits cognitivos podem ser consequentes à diminuição dos níveis de glutamato, relatando inclusive que os sintomas cognitivos podem ser aliviados com a utilização de glutationa e N-acetilcisteína 21 .…”

Section: Fisiopatologiaunclassified

“…No que se refere aos domínios cognitivos afetados, os mais relatados foram disfunção executiva 12,13,14,16,20,21,22 , velocidade de processamento 12,19, e memória em geral 12,16,21 , incluindo memória de curto 17 e longo prazo 14,20 , de trabalho 17,22 , verbal e espacial 19 . Esses achados são semelhantes aos encontrados em pacientes após SDRA por outras etiologias, onde se sugere que os danos cognitivos sejam resultado da hipóxia, atingindo áreas cerebrais sensíveis e responsáveis por tais funções como o lobo medial temporal 19 e hipocampo 22 e da elevada liberação de citocinas inflamatórias, causando danos neuronais.…”

Section: Domínios Cognitivos Afetadosunclassified

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Disfunção cognitiva e infecção por SARS-CoV-2: Revisão Integrativa / Cognitive Dysfunction and SARS-CoV-2 Infection: Integrative Review

Lima¹,

Silva²,

Pinto³

2021

BJDV

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No final do ano de 2019 observou-se o surgimento de um novo vírus denominado ''coronavírus 2'', da Síndrome da Angústia Respiratória Aguda Grave (SARS-CoV-2), em Wuhan, China, que em pouco tempo ocasionou uma pandemia global. A partir da detecção dos casos, o aparecimento de diversas alterações cognitivas começou a ser associado ao processo infeccioso e às suas sequelas, emergindo diversas pesquisas na área. Foi realizada uma revisão integrativa nas bases de dados MEDLINE/PubMed, SciELO, LILACS e WEB OF SCIENCE, obedecendo seis etapas metodológicas, para analisar a relação entre o SARS-CoV-2 e déficit cognitivo em maiores de 18 anos. Após a realização da pesquisa, apenas 11 artigos cumpriram os critérios e foram utilizados para compor a revisão integrativa. Dentre os processos fisiopatológicos envolvidos, a hipóxia e a neuroinflamação aparecem como fatores causais, e a região do hipocampo como umas das principais áreas cerebrais acometidas. No que se refere aos domínios cognitivos afetados, os mais relatados foram: disfunção executiva, velocidade de processamento e memória em geral. A grande maioria das pesquisas analisadas possuem fragilidades metodológicas que impossibilitam a generalização dos resultados com um alto grau de confiabilidade. Os distúrbios relatados estão presentes tanto na fase aguda quanto meses após a infecção, podendo interferir na vida dos indivíduos, sendo recomendado o acompanhamento neurológico e reabilitação cognitiva em pacientes selecionados.

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“…During the course of coronavirus disease-2019 (COVID-19) pandemic, many neuropsychiatric manifestations of the disease have been observed while the precise pathophysiology remains unknown ( Sen et al, 2021 ; Yesilkaya et al, 2021 ). New variants of coronavirus such as the 501.V2 and B.1.1.7 have emerged and obscurities in pathogenesis have increased even further with these variants.…”

mentioning

confidence: 99%

New variants and new symptoms in COVID-19: First episode psychosis and Cotard's Syndrome two months after infection with the B.1.1.7 variant of coronavirus

Yeşilkaya

Sen

Karamustafalıoğlu

2022

Schizophrenia Research

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COVID-19-related cognitive dysfunction may be associated with transient disruption in the DLPFC glutamatergic pathway

Cited by 23 publications

References 13 publications

SARS-CoV-2 Infection Impacts Carbon Metabolism and Depends on Glutamine for Replication in Syrian Hamster Astrocytes

SARS-CoV-2 Infection Impacts Carbon Metabolism and Depends on Glutamine for Replication in Syrian Hamster Astrocytes

Disfunção cognitiva e infecção por SARS-CoV-2: Revisão Integrativa / Cognitive Dysfunction and SARS-CoV-2 Infection: Integrative Review

New variants and new symptoms in COVID-19: First episode psychosis and Cotard's Syndrome two months after infection with the B.1.1.7 variant of coronavirus

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