N-3 polyunsaturated fatty acids and clozapine abrogates poly I: C-induced immune alterations in primary hippocampal neurons

Ribeiro, B.M.M.; Filho, Adriano José Maia Chaves; Costa, Deiziane Viana da Silva; Menezes, A.T.; Fonseca, Anna Carolina Carvalho da; Gama, Clarissa Severino; Neto, Vivaldo Moura; Lucena, David Freitas de; Vale, Mariana Lima; Macêdo, Danielle Silveira

doi:10.1016/j.pnpbp.2018.11.022

Cited by 16 publications

(8 citation statements)

References 73 publications

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“…This antipsychotic drug has been reported to exhibit anti-in ammatory activities, and decrease astrocyte and microglial activation [61,62]. Thus, clozapine protects neurons from the in ammatory changes induced by poly I:C and prevents increases in interleukin-6 levels in the rodent brain [63,64]. Behavioral abnormalities in sH-2D-expressing mice as well as their sensitivity to clozapine suggest their face and predictive validities as an animal model of schizophrenia.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Astroglial Major Histocompatibility Complex Class I in the Medial Prefrontal Cortex Impairs Visual Discrimination Learning in Mice

Wulaer

Hada

Sobue

et al. 2020

Preprint

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Background Immune molecules, such as cytokines, complement, and major histocompatibility complex (MHC) proteins, in the central nervous system are often associated with neuropsychiatric disorders. Neuronal MHC class I (MHCI), such as H-2D, regulate neurite outgrowth, the establishment and function of cortical connections, and activity-dependent refinement in mice. We previously established mice expressing MHCI specifically in astrocytes of the media prefrontal cortex (mPFC) using the adeno-associated virus (AAV) vector under the control of the glial fibrillary acidic protein (GFAP) promoter. Mice expressing the soluble form of H-2D (sH-2D) in the mPFC (sH-2D-expressing mice) showed abnormal behaviors, including social interaction deficits and cognitive dysfunctions. However, the pathophysiological significance of astroglial MHCI on higher brain functions remains unclear. Therefore, cognitive function in mice expressing sH-2D in astrocytes of the mPFC was tested using the visual discrimination (VD) task to assess the impact of the astrocyte pathology and resulting behavioral changes.Methods Three separate batches of mice were used in the present study. sH-2D-expressing mice were subjected to the VD and reversal learning tasks, morphological analyses, and pharmacological intervention using clozapine in the social interaction and novel object recognition tasks.Results In pretraining, the performance of sH-2D-expressing mice was normal in response phase sessions (stages 1–4), but impaired in the punish phase session (stage 5). The total numbers of sessions, trials, normal trials, and correction trials to reach the VD criterion were significantly higher in sH-2D-expressing mice than in control mice. A morphological study showed that dendritic complexity was significantly reduced in the dorsal striatum of sH-2D-expressing mice. A treatment with clozapine ameliorated decreased social behavior as well as impaired object recognition memory in sH-2D-expressing mice.Conclusion Collectively, the present results suggest that the overexpression of astroglial MHCI in the mPFC results in impaired VD learning, which may be accompanied by decreased dendritic complexity in the dorsal striatum and mPFC.

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Section: Discussionmentioning

confidence: 99%

Overexpression of Astroglial Major Histocompatibility Complex Class I in the Medial Prefrontal Cortex Impairs Visual Discrimination Learning in Mice

Wulaer

Hada

Sobue

et al. 2020

Preprint

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Section: Effects Of N-3 Pufas In Various Neuropsychiatric Disordersmentioning

confidence: 99%

“…18 In an in vitro model mimicking the involvement of viral infection in the development of neuropsychiatric disorders, n-3 PUFAs showed significant neuroprotective effects. 86 In addition, clinical studies in schizophrenic patients found that n-3 PUFA substitution leads to an increase in telomerase levels as well as a reduction in oxidative stress. 84,87,88 ADHD It is well established that dietary depletion of n-3 PUFAs during fetal development and early childhood may have adverse effects on brain development, neurodevelopmental outcomes, and cognitive health.…”

Section: Depressionmentioning

confidence: 99%

The emerging role of omega-3 fatty acids as a therapeutic option in neuropsychiatric disorders

Reimers

Ljung

2019

Therapeutic Advances in Psychopharmacology

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Research on omega-3 polyunsaturated fatty acids (n-3 PUFAs) has grown exponentially since researchers from Denmark visited Greenland in 1970 to study why the cardiovascular mortality among the Inuit population was considerably lower than in the Western countries. 6 The researchers related their findings to the diet of the Inuit, which consisted mainly of fish and meat from seals, whales, sea birds, and fur-bearing animals. These foods contain large amounts of n-3 PUFAs. 6 In the following decades, the health effects of n-3 PUFAs were studied extensively, covering almost all medical conditions, including

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“…Ribeiro et al. reported that omega-3 PUFAs (n3 PUFAs), but not clozapine, prevented polyinosinic:polycytidylic acid (poly I:C)-induced deficits in BDNF (Ribeiro et al., 2019). Because decreased BDNF-TrkB signaling has been suggested to play a role in the pathophysiology of schizophrenia (Giovanoli et al., 2015; Han et al., 2016), and sEH inhibitors increase the level of BDNF, it appears that sEH may play a role in schizophrenia via regulation of the BDNF-TrkB signaling pathway.…”

Section: Role Of Seh In Psychiatric Disordersmentioning

confidence: 99%

Soluble Epoxide Hydrolase Inhibitor: A Novel Potential Therapeutic or Prophylactic Drug for Psychiatric Disorders

Ren

2019

Front. Pharmacol.

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Psychiatric disorders, including depression and schizophrenia, affect millions of individuals worldwide. However, the precise neurobiology of psychiatric disorders remains unclear. Accumulating evidence suggests that various inflammatory processes play a key role in depression and schizophrenia, and that anti-inflammatory drugs exert a therapeutic effect in patients with psychiatric disorders. Epoxyeicosatrienoic acids (EETs) and epoxydocosapentaenoic acids (EDPs) have potent anti-inflammatory properties. These mediators are broken down into their corresponding diols by soluble epoxide hydrolase (sEH), and inhibition of sEH enhances the anti-inflammatory effects of EETs. Therefore, sEH may play a key role in inflammation, which is involved in psychiatric disorders. Recent studies have shown that abnormal levels of sEH may be involved in the pathogenesis of certain psychiatric diseases, and that sEH inhibitors exhibit antidepressant and antipsychotic activity. The present review discusses the extensive evidence supporting sEH as a therapeutic target for psychiatric diseases, and the clinical value of sEH inhibitors as therapeutic or prophylactic drugs.

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N-3 polyunsaturated fatty acids and clozapine abrogates poly I: C-induced immune alterations in primary hippocampal neurons

Cited by 16 publications

References 73 publications

Overexpression of Astroglial Major Histocompatibility Complex Class I in the Medial Prefrontal Cortex Impairs Visual Discrimination Learning in Mice

Overexpression of Astroglial Major Histocompatibility Complex Class I in the Medial Prefrontal Cortex Impairs Visual Discrimination Learning in Mice

The emerging role of omega-3 fatty acids as a therapeutic option in neuropsychiatric disorders

Soluble Epoxide Hydrolase Inhibitor: A Novel Potential Therapeutic or Prophylactic Drug for Psychiatric Disorders

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