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  1. AU="Dunn, Geoffrey A"
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  1. Article ; Online: The Influence of Maternal Metabolic State and Nutrition on Offspring Neurobehavioral Development: A Focus on Preclinical Models.

    Mitchell, A J / Dunn, Geoffrey A / Sullivan, Elinor L

    Biological psychiatry. Cognitive neuroscience and neuroimaging

    2021  Volume 7, Issue 5, Page(s) 450–460

    Abstract: The prevalence of both obesity and neurodevelopmental disorders has increased substantially over the last several decades. Early environmental factors, including maternal nutrition and metabolic state during gestation, influence offspring ... ...

    Abstract The prevalence of both obesity and neurodevelopmental disorders has increased substantially over the last several decades. Early environmental factors, including maternal nutrition and metabolic state during gestation, influence offspring neurodevelopment. Both human and preclinical models demonstrate a link between poor maternal nutrition, altered metabolic state, and risk of behavioral abnormalities in offspring. This review aims to highlight evidence from the current literature connecting maternal nutrition and the associated metabolic changes with neural and behavioral outcomes in the offspring, as well as identify possible mechanisms underlying these neurodevelopmental outcomes. Owing to the highly correlated nature of poor nutrition and obesity in humans, preclinical animal models are important in distinguishing the unique effects of maternal nutrition and metabolic state on offspring brain development. We use a translational lens to highlight results from preclinical animal models of maternal obesogenic diet related to alterations in behavioral and neurodevelopmental outcomes in offspring. Specifically, we aim to highlight results that resemble behavioral phenotypes described in the diagnostic criteria of neurodevelopmental conditions in humans. Finally, we examine the proinflammatory nature of maternal obesity and consumption of a high-fat diet as a mechanism for neurodevelopmental alterations that may alter offspring behavior later in life. It is important that future studies examine potential therapeutic interventions and prevention strategies to interrupt the transgenerational transmission of the disease. Given the tremendous risk to the next generation, changes need to be made to ensure that all pregnant people have access to nutritious food and are informed about the optimal diet for their developing child.
    MeSH term(s) Animals ; Diet, High-Fat/adverse effects ; Female ; Humans ; Maternal Nutritional Physiological Phenomena ; Neurodevelopmental Disorders/etiology ; Obesity/complications ; Obesity/metabolism ; Pregnancy ; Prenatal Exposure Delayed Effects
    Language English
    Publishing date 2021-12-13
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural
    ZDB-ID 2879089-3
    ISSN 2451-9030 ; 2451-9022
    ISSN (online) 2451-9030
    ISSN 2451-9022
    DOI 10.1016/j.bpsc.2021.11.014
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  2. Article ; Online: Neuroinflammation in psychiatric disorders: An introductory primer.

    Dunn, Geoffrey A / Loftis, Jennifer M / Sullivan, Elinor L

    Pharmacology, biochemistry, and behavior

    2020  Volume 196, Page(s) 172981

    MeSH term(s) Humans ; Inflammation/complications ; Inflammation/metabolism ; Mental Disorders/complications ; Mental Disorders/metabolism ; Nervous System Diseases/complications ; Nervous System Diseases/metabolism
    Language English
    Publishing date 2020-07-01
    Publishing country United States
    Document type Editorial ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 191042-5
    ISSN 1873-5177 ; 0091-3057
    ISSN (online) 1873-5177
    ISSN 0091-3057
    DOI 10.1016/j.pbb.2020.172981
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1060: Show issues Location:
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  3. Article: Perinatal Western-style diet alters serotonergic neurons in the macaque raphe nuclei.

    Dunn, Geoffrey A / Thompson, Jacqueline R / Mitchell, A J / Papadakis, Samantha / Selby, Matthew / Fair, Damien / Gustafsson, Hanna C / Sullivan, Elinor L

    Frontiers in neuroscience

    2023  Volume 16, Page(s) 1067479

    Abstract: Introduction: The neurotransmitter serotonin is a key regulator of neurotransmission, mood, and behavior and is essential in neurodevelopment. Dysfunction in this important neurotransmitter system is connected to behavioral disorders such as depression ... ...

    Abstract Introduction: The neurotransmitter serotonin is a key regulator of neurotransmission, mood, and behavior and is essential in neurodevelopment. Dysfunction in this important neurotransmitter system is connected to behavioral disorders such as depression and anxiety. We have previously shown that the developing serotonin system is sensitive to perinatal exposure to Western-style diet (WSD).
    Methods: To advance our hypothesis that perinatal WSD has a long-term impact on the serotonergic system, we designed a fluorescent immunohistochemistry experiment using antibodies against tryptophan hydroxylase 2 (TPH2) and vesicular glutamate transporter 3 (VGLUT3) to probe protein expression in the raphe subnuclei in 13-month-old Japanese macaques (
    Results: In this immunohistochemical study, we provide the most detailed characterization of the developing primate raphe to date. We utilize multi-level modeling (MLM) to simultaneously probe the contribution of WSD, offspring sex, and raphe anatomical location, to raphe neuronal measurements. Our molecular and morphological characterization revealed that the 13-month-old macaque DR is remarkably similar to that of adult macaques and humans. We demonstrate that vesicular glutamate transporter 3 (VGLUT3), which rodent studies have recently shown can distinguish raphe populations with distinct projection targets and behavioral functions, likewise contributes to the heterogeneity of the primate raphe.
    Discussion: This study provides evidence that perinatal WSD has a long-term impact on the density of serotonin-producing neurons, potentially limiting serotonin availability throughout the brain. Due to the critical involvement of serotonin in development and behavior, these findings provide important insight into the mechanisms by which maternal nutrition and metabolic state influence offspring behavioral outcomes. Finally, these findings could inform future research focused on designing therapeutic interventions to optimize neural development and decrease a child's risk of developing a mental health disorder.
    Language English
    Publishing date 2023-01-10
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2411902-7
    ISSN 1662-453X ; 1662-4548
    ISSN (online) 1662-453X
    ISSN 1662-4548
    DOI 10.3389/fnins.2022.1067479
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  4. Article ; Online: Perinatal Western-style diet exposure associated with decreased microglial counts throughout the arcuate nucleus of the hypothalamus in Japanese macaques.

    Papadakis, Samantha / Thompson, Jacqueline R / Feczko, Eric / Miranda-Dominguez, Oscar / Dunn, Geoffrey A / Selby, Matthew / Mitchell, A J / Sullivan, Elinor L / Fair, Damien A

    Journal of neurophysiology

    2024  Volume 131, Issue 2, Page(s) 241–260

    Abstract: Perinatal exposure to a high-fat, high-sugar Western-style diet (WSD) is associated with altered neural circuitry in the melanocortin system. This association may have an underlying inflammatory component, as consumption of a WSD during pregnancy can ... ...

    Abstract Perinatal exposure to a high-fat, high-sugar Western-style diet (WSD) is associated with altered neural circuitry in the melanocortin system. This association may have an underlying inflammatory component, as consumption of a WSD during pregnancy can lead to an elevated inflammatory environment. Our group previously demonstrated that prenatal WSD exposure was associated with increased markers of inflammation in the placenta and fetal hypothalamus in Japanese macaques. In this follow-up study, we sought to determine whether this heightened inflammatory state persisted into the postnatal period, as prenatal exposure to inflammation has been shown to reprogram offspring immune function and long-term neuroinflammation would present a potential means for prolonged disruptions to microglia-mediated neuronal circuit formation. Neuroinflammation was approximated in 1-yr-old offspring by counting resident microglia and peripherally derived macrophages in the region of the hypothalamus examined in the fetal study, the arcuate nucleus (ARC). Microglia and macrophages were immunofluorescently stained with their shared marker, ionized calcium-binding adapter molecule 1 (Iba1), and quantified in 11 regions along the rostral-caudal axis of the ARC. A mixed-effects model revealed main effects of perinatal diet (
    MeSH term(s) Pregnancy ; Animals ; Female ; Arcuate Nucleus of Hypothalamus ; Macaca fuscata ; Microglia ; Neuroinflammatory Diseases ; Follow-Up Studies ; Hypothalamus ; Diet, High-Fat/adverse effects ; Macaca
    Language English
    Publishing date 2024-01-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80161-6
    ISSN 1522-1598 ; 0022-3077
    ISSN (online) 1522-1598
    ISSN 0022-3077
    DOI 10.1152/jn.00213.2023
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    Uc I Zs.224: Show issues Location:
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  5. Article ; Online: Neuroinflammation as a risk factor for attention deficit hyperactivity disorder.

    Dunn, Geoffrey A / Nigg, Joel T / Sullivan, Elinor L

    Pharmacology, biochemistry, and behavior

    2019  Volume 182, Page(s) 22–34

    Abstract: Attention Deficit Hyperactivity Disorder (ADHD) is a persistent, and impairing pediatric-onset neurodevelopmental condition. Its high prevalence, and recurrent controversy over its widespread identification and treatment, drive strong interest in its ... ...

    Abstract Attention Deficit Hyperactivity Disorder (ADHD) is a persistent, and impairing pediatric-onset neurodevelopmental condition. Its high prevalence, and recurrent controversy over its widespread identification and treatment, drive strong interest in its etiology and mechanisms. Emerging evidence for a role for neuroinflammation in ADHD pathophysiology is of great interest. This evidence includes 1) the above-chance comorbidity of ADHD with inflammatory and autoimmune disorders, 2) initial studies indicating an association with ADHD and increased serum cytokines, 3) preliminary evidence from genetic studies demonstrating associations between polymorphisms in genes associated with inflammatory pathways and ADHD, 4) emerging evidence that early life exposure to environmental factors may increase risk for ADHD via an inflammatory mechanism, and 5) mechanistic evidence from animal models of maternal immune activation documenting behavioral and neural outcomes consistent with ADHD. Prenatal exposure to inflammation is associated with changes in offspring brain development including reductions in cortical gray matter volume and the volume of certain cortical areas -parallel to observations associated with ADHD. Alterations in neurotransmitter systems, including the dopaminergic, serotonergic and glutamatergic systems, are observed in ADHD populations. Animal models provide strong evidence that development and function of these neurotransmitters systems are sensitive to exposure to in utero inflammation. In summary, accumulating evidence from human studies and animal models, while still incomplete, support a potential role for neuroinflammation in the pathophysiology of ADHD. Confirmation of this association and the underlying mechanisms have become valuable targets for research. If confirmed, such a picture may be important in opening new intervention routes.
    MeSH term(s) Adolescent ; Animals ; Attention Deficit Disorder with Hyperactivity/etiology ; Attention Deficit Disorder with Hyperactivity/immunology ; Attention Deficit Disorder with Hyperactivity/metabolism ; Attention Deficit Disorder with Hyperactivity/physiopathology ; Central Nervous System/embryology ; Central Nervous System/growth & development ; Central Nervous System/physiopathology ; Child ; Cytokines/metabolism ; Dopamine/metabolism ; Female ; Glutamic Acid/metabolism ; Humans ; Inflammation/complications ; Inflammation/immunology ; Inflammation/metabolism ; Male ; Mice ; Models, Animal ; Norepinephrine/metabolism ; Pregnancy ; Prenatal Exposure Delayed Effects ; Risk Factors ; Serotonin/metabolism ; Young Adult ; gamma-Aminobutyric Acid/metabolism
    Chemical Substances Cytokines ; Serotonin (333DO1RDJY) ; Glutamic Acid (3KX376GY7L) ; gamma-Aminobutyric Acid (56-12-2) ; Dopamine (VTD58H1Z2X) ; Norepinephrine (X4W3ENH1CV)
    Language English
    Publishing date 2019-05-16
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 191042-5
    ISSN 1873-5177 ; 0091-3057
    ISSN (online) 1873-5177
    ISSN 0091-3057
    DOI 10.1016/j.pbb.2019.05.005
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    In stock of ZB MED Cologne/Königswinter

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  6. Article: The association between heightened ADHD symptoms and cytokine and fatty acid concentrations during pregnancy.

    Gustafsson, Hanna C / Dunn, Geoffrey A / Mitchell, A J / Holton, Kathleen F / Loftis, Jennifer M / Nigg, Joel T / Sullivan, Elinor L

    Frontiers in psychiatry

    2022  Volume 13, Page(s) 855265

    Abstract: Objective: Previous research conducted with samples of children suggest that individuals with attention-deficit/hyperactivity disorder (ADHD) have altered fatty acid concentrations and may have increased systemic inflammation. Whether these differences ... ...

    Abstract Objective: Previous research conducted with samples of children suggest that individuals with attention-deficit/hyperactivity disorder (ADHD) have altered fatty acid concentrations and may have increased systemic inflammation. Whether these differences are also apparent in other populations of individuals with heightened ADHD symptoms (e.g., pregnant adults) is unknown. The goal of the current study was to examine whether there are ADHD-associated differences in polyunsaturated fatty acid concentrations or pro-inflammatory cytokine concentrations during pregnancy, a developmental period when fatty acid concentrations and systemic inflammation have implications for the health of both the pregnant person and the developing child. We hypothesized that plasma levels of the ratio of omega-6s to omega-3s (n-6:n-3) and plasma inflammatory cytokine levels would be higher in individuals with heightened ADHD symptoms, consistent with previous findings in children with ADHD.
    Methods: Data (
    Results: The group with heightened ADHD symptoms had higher n-6:n-3s (β = 0.30,
    Conclusion: Pregnant individuals with ADHD, on average, had higher plasma n-6:n-3s and higher TNF-α concentrations relative to controls. A difference was not detected in their dietary intake of fatty acids or other relevant nutrients. Though these null findings are inconclusive, they are consistent with the hypothesis that ADHD-associated differences in plasma fatty acid concentrations are the result of ADHD-associated differences in fatty acid metabolism, rather than simply differences in dietary intake.
    Language English
    Publishing date 2022-07-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2564218-2
    ISSN 1664-0640
    ISSN 1664-0640
    DOI 10.3389/fpsyt.2022.855265
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  7. Article ; Online: Maternal diet and obesity shape offspring central and peripheral inflammatory outcomes in juvenile non-human primates.

    Dunn, Geoffrey A / Mitchell, A J / Selby, Matthew / Fair, Damien A / Gustafsson, Hanna C / Sullivan, Elinor L

    Brain, behavior, and immunity

    2022  Volume 102, Page(s) 224–236

    Abstract: The obesity epidemic affects 40% of adults in the US, with approximately one-third of pregnant women classified as obese. Previous research suggests that children born to obese mothers are at increased risk for a number of health conditions. The ... ...

    Abstract The obesity epidemic affects 40% of adults in the US, with approximately one-third of pregnant women classified as obese. Previous research suggests that children born to obese mothers are at increased risk for a number of health conditions. The mechanisms behind this increased risk are poorly understood. Increased exposure to in-utero inflammation induced by maternal obesity is proposed as an underlying mechanism for neurodevelopmental alterations in offspring. Utilizing a non-human primate model of maternal obesity, we hypothesized that maternal consumption of an obesogenic diet will predict offspring peripheral (e.g., cytokines and chemokines) and central (microglia number) inflammatory outcomes via the diet's effects on maternal adiposity and maternal inflammatory state during the third trimester. We used structural equation modeling to simultaneously examine the complex associations among maternal diet, metabolic state, adiposity, inflammation, and offspring central and peripheral inflammation. Four latent variables were created to capture maternal chemokines and pro-inflammatory cytokines, and offspring cytokine and chemokines. Model results showed that offspring microglia counts in the basolateral amygdala were associated with maternal diet (β = -0.622, p < 0.01), adiposity (β = 0.593, p < 0.01), and length of gestation (β = 0.164, p < 0.05) but not with maternal chemokines (β = 0.135, p = 0.528) or maternal pro-inflammatory cytokines (β = 0.083, p = 0.683). Additionally, we found that juvenile offspring peripheral cytokines (β = -0.389, p < 0.01) and chemokines (β = -0.298, p < 0.05) were associated with a maternal adiposity-induced decrease in maternal circulating chemokines during the third trimester (β = -0.426, p < 0.01). In summary, these data suggest that maternal diet and adiposity appear to directly predict offspring amygdala microglial counts while maternal adiposity influences offspring peripheral inflammatory outcomes via maternal inflammatory state.
    MeSH term(s) Adiposity ; Animals ; Chemokines/metabolism ; Cytokines/metabolism ; Diet ; Diet, High-Fat/adverse effects ; Female ; Humans ; Inflammation ; Obesity/metabolism ; Obesity, Maternal ; Pregnancy ; Prenatal Exposure Delayed Effects/metabolism ; Primates/metabolism
    Chemical Substances Chemokines ; Cytokines
    Language English
    Publishing date 2022-02-22
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 639219-2
    ISSN 1090-2139 ; 0889-1591
    ISSN (online) 1090-2139
    ISSN 0889-1591
    DOI 10.1016/j.bbi.2022.02.024
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