BXD recombinant inbred strains participate in social preference, anxiety and depression behaviors along sex-differences in cytokines and tactile allodynia

López-Granero, Caridad; Santos, Alessandra Antunes dos; Ferrer, Bertha Beatriz Socarrás; Culbreth, Megan; Chakraborty, Sudipta; Barrasa, Ángel; Gulinello, Maria; Bowman, Aaron B.; Aschner, Michael

doi:10.1016/j.psyneuen.2017.03.006

Cited by 8 publications

(14 citation statements)

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“…Increased serum levels of TNF-α and IL-6 have been shown in two different BXD mouse lineages that are commonly used as genetic resources to study neuropharmacological phenomenon (Philip et al, 2010). In BXD21/TyJ RI mice, nuclear factor erythroid 2 (Nrf2) expression is upregulated, while BXD84/RwwJ RI mice exhibit low Nrf2 expression (López-Granero et al, 2017). Considering the role of Nrf2 in activating antioxidative mechanisms (Zhang et al, 2013), these mice show greater depressive-like behavior than wild-type mice (López-Granero et al, 2017).…”

Section: Target Structures Involved In Pain and Depressionmentioning

confidence: 99%

Neuroinflammation, Pain and Depression: An Overview of the Main Findings

et al. 2020

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Chronic pain is a serious public health problem with a strong affective-motivational component that makes it difficult to treat. Most patients with chronic pain suffer from severe depression; hence, both conditions coexist and exacerbate one another. Brain inflammatory mediators are critical for maintaining depression-pain syndrome and could be substrates for it. The goal of our paper was to review clinical and preclinical findings to identify the neuroinflammatory profile associated with the cooccurrence of pain and depression. In addition, we aimed to explore the regulatory effect of neuronal reorganization on the inflammatory response in pain and depression. We conducted a quantitative review supplemented by manual screening. Our results revealed inflammatory signatures in different preclinical models and clinical articles regarding depression-pain syndrome. We also identified that improvements in depressive symptoms and amelioration of pain can be modulated through direct targeting of inflammatory mediators, such as cytokines and molecular inhibitors of the inflammatory cascade. Additionally, therapeutic targets that improve and regulate the synaptic environment and its neurotransmitters may act as anti-inflammatory compounds, reducing local damage-associated molecular patterns and inhibiting the activation of immune and glial cells. Taken together, our data will help to better elucidate the neuroinflammatory profile in pain and depression and may help to identify pharmacological targets for effective management of depression-pain syndrome.

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Section: Target Structures Involved In Pain and Depressionmentioning

confidence: 99%

Neuroinflammation, Pain and Depression: An Overview of the Main Findings

et al. 2020

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“…Previously, we have demonstrated that certain inflammatory responses could be desirable in mitigating psychiatric disorders, such as depressive behavior. We have observed that the BXD21/TyJ strain exhibited lessened immobility time in the forced swim test, congruent with lessened depression-like behavior 20 . Concomitantly, we noted overexpression of cerebral cortex proinflammatory cytokines, (tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6)) in the absence of oxidative stress 20 .…”

mentioning

confidence: 53%

“…Here, we chose the BXD84/RwwJ RI and BXD21/TyJ strains given their diverse expression lof Nrf2 mRNA. In an earlier report, we have demonstrated low expression of Nrf2 mRNA in the BXD84/RwwJRI strain and its high expression in BXD21/TyJ RI strain at postnatal day 21 20 . Since the BXD RI mouse strains and Nrf2 might offer an optimal platform for relating genetic influences with environmental exposure outcomes, the understanding of the relationship between BXD RI mice and Nrf2 is essential.…”

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confidence: 66%

“…Total RNA from the cerebellum, hippocampus and striatum was extracted with Trizol (Life Technologies) as previously described 20 . Briefly, chloroform was added to each sample.…”

Section: Gene Expression Assay By Taqman Methodmentioning

confidence: 99%

“…However, here we have demonstrated overproduction of inflammatory cytokines accompanied by lower brain weight in BXD RI strain. Previously, we have indicated that the inflammation might be a double-edged sword in the BXD RI strain 20 , the contribution to behavioral alterations and as effective therapeutic target via astrogliosis function 43 . The lesser brain weight observed could be indicating an attempt to regulate the inflammatory response in the BXD21/TyJ RI strain as a protective mechanism.…”

Section: Bxd84/rwwj Ri and Control Mice Do Not Show An Innate Change mentioning

confidence: 99%

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The BXD21/TyJ recombinant inbred strain as a model for innate inflammatory response in distinct brain regions

López-Granero

Ferrer

Santos

et al. 2020

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Oxidative stress and inflammatory cytokines affect the human brain, increasing the risk for mood and cognitive disorders. Such risk might be selective to brain-specific regions. Here, we determined whether BXD recombinant inbred (RI) mice strains are more suitable than C57BL/6J mice for the understanding of the relationship between antioxidant response and inflammatory responses. We hypothesized that inflammatory responses could be independent of antioxidant response and be inherent to brain-specific regions. This hypothesis will be addressed by the analyses of mRNA expression. We explored, at 7-months-of-age, the innate activation of proinflammatory cytokines (tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6), as well as Kelch-like ECH-associating protein 1 (Keap1), nuclear factor erythroid 2 related factor 2 (Nrf2) and glutathione peroxidase 1 (Gpx1) mRNA in both male and female BXD84/RwwJ RI, BXD21/TyJ RI and control strain (C57BL/6J mice). We report that: (1) The cerebellum is more sensitive to antioxidant response in the BXD21/TyJ RI strain; (2) The cerebellum, hippocampus and striatum show increased levels of cytokines in the BXD21/TyJ RI strain; (3) The BXD RI strain has lower brain weight relative to control strain (C57BL/6 mice). In conclusion, our novel data show the utility of the BXD21/TyJ RI strain mice in offering mechanistic insight into Nrf2's role in the inflammatory system. Central nervous system (CNS) dysfunction is frequently accompanied by oxidative stress and inflammatory responses 1. Oxidative damage and inflammatory cytokines influence brain function and result in increased risk for mood, behavioral and cognitive disorders 2-4. Thus, the general hypothesis is that antioxidant defenses and inflammatory cytokines are key elements in CNS pathologies 5 and psychiatric disorders 3,4,6,7. Several studies have revealed the mechanism by which continued oxidative stress can lead to chronic inflammation, which, in turn, could mediate most chronic diseases 8. The disruption of the inflammatory and oxidative stress pathways is associated with multiple neurotoxic exposures 9-11. Oxidative stress acts activating a variety of transcription factors, including Nrf2. Upon oxidative stress generation, Nrf2 dissociates from Kelch-like ECH-associating protein 1 (Keap1), and translocates into the nucleus where it binds to the antioxidant response element (ARE), and initiates antioxidant gene transcription thus restoring cellular redox homeostasis 12-15. Activation of these transcription factors can lead to the expression of different genes, including those for inflammatory cytokines and anti-inflammatory molecules 8. Indeed, Nrf2 is essential for protection against oxidative stress and it has also been shown to attenuate inflammation 16. Consistent with these observations, published data have corroborated dysregulation of inflammatory and oxidative systems both in behavioral and psychiatric disorders as a consequence of altered Nrf2 pathway functioning 7,15. Neuroinflammatory processes are established...

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Haploinsufficiency in the ANKS1B gene encoding AIDA-1 leads to a neurodevelopmental syndrome

et al. 2019

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Neurodevelopmental disorders, including autism spectrum disorder, have complex polygenic etiologies. Single-gene mutations in patients can help define genetic factors and molecular mechanisms underlying neurodevelopmental disorders. Here we describe individuals with monogenic heterozygous microdeletions in ANKS1B , a predicted risk gene for autism and neuropsychiatric diseases. Affected individuals present with a spectrum of neurodevelopmental phenotypes, including autism, attention-deficit hyperactivity disorder, and speech and motor deficits. Neurons generated from patient-derived induced pluripotent stem cells demonstrate loss of the ANKS1B -encoded protein AIDA-1, a brain-specific protein highly enriched at neuronal synapses. A transgenic mouse model of Anks1b haploinsufficiency recapitulates a range of patient phenotypes, including social deficits, hyperactivity, and sensorimotor dysfunction. Identification of the AIDA-1 interactome using quantitative proteomics reveals protein networks involved in synaptic function and the etiology of neurodevelopmental disorders. Our findings formalize a link between the synaptic protein AIDA-1 and a rare, previously undefined genetic disease we term ANKS1B haploinsufficiency syndrome.

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BXD recombinant inbred strains participate in social preference, anxiety and depression behaviors along sex-differences in cytokines and tactile allodynia

Cited by 8 publications

References 40 publications

Neuroinflammation, Pain and Depression: An Overview of the Main Findings

Neuroinflammation, Pain and Depression: An Overview of the Main Findings

The BXD21/TyJ recombinant inbred strain as a model for innate inflammatory response in distinct brain regions

Haploinsufficiency in the ANKS1B gene encoding AIDA-1 leads to a neurodevelopmental syndrome

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