Maternal immune activation alters social affective behavior and sensitivity to corticotropin releasing factor in male but not female rats

Rieger, Nathaniel S.; Ng, Alexandra J.; Lee, Shanon; Brady, Bridget H; Christianson, John P.

doi:10.1016/j.yhbeh.2023.105313

Cited by 4 publications

(3 citation statements)

References 61 publications

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“…Any deviation from this sequence may potentially alter brain formation and functions and therefore precipitate pathological conditions that often do not manifest until later in life. Accordingly, perinatal stress consequences have been observed in the offspring only at adulthood both in preclinical and clinical settings − and the same occurs after other types of manipulations such as prenatal infection. − In line, it is possible to hypothesize that, despite the latency in the manifestation of the pathological conditions, molecular alterations may be already present but remain below threshold, leading to increased vulnerability and an inability to cope with a subsequent challenging event.…”

Section: Introductionmentioning

confidence: 97%

Prenatal Fluoxetine Exposure Influences Glucocorticoid Receptor-Mediated Activity in the Prefrontal Cortex of Adolescent Rats Exposed to Acute Stress

Gallo,

Dolci,

Fumagalli

et al. 2024

ACS Chem. Neurosci.

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Any deviation from the programmed processes of brain development may modify its formation and functions, thereby precipitating pathological conditions, which often become manifest in adulthood. Exposure to a challenge during crucial periods of vulnerability, such as adolescence, may reveal molecular changes preceding behavioral outcomes. Based on a previous study showing that prenatal fluoxetine (FLX) leads to the development of an anhedonic-like behavior in adult rats, we aimed to assess whether the same treatment regimen (i.e., fluoxetine during gestation; 15 mg/kg/day) influences the ability to respond to acute restraint stress (ARS) during adolescence. We subjected the rats to a battery of behavioral tests evaluating the development of various phenotypes (cognitive deficit, anhedonia, and anxiety). Furthermore, we carried out molecular analyses in the plasma and prefrontal cortex, a brain region involved in stress response, and whose functions are commonly altered in neuropsychiatric conditions. Our findings confirm that prenatal manipulation did not affect behavior in adolescent rats but impaired the capability to respond properly to ARS. Indeed, we observed changes in several molecular key players of the hypothalamic pituitary adrenal axis, particularly influencing genomic effects mediated by the glucocorticoid receptor. This study highlights that prenatal FLX exposure influences the ability of adolescent male rats to respond to an acute challenge, thereby altering the functionality of the hypothalamic-pituitary-adrenal axis, and indicates that the prenatal manipulation may prime the response to challenging events during this critical period of life.

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Section: Introductionmentioning

confidence: 97%

Prenatal Fluoxetine Exposure Influences Glucocorticoid Receptor-Mediated Activity in the Prefrontal Cortex of Adolescent Rats Exposed to Acute Stress

Gallo,

Dolci,

Fumagalli

et al. 2024

ACS Chem. Neurosci.

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“…34 This occurred in a sex-dependent manner in some studies where social-like behavior is altered in only juvenile males exposed to MIA 35 where other studies demonstrate social deficits in adult male and female offspring. [36][37][38] The current MIA study used a TLR7/8 agonist, Resiquimod (RQ).…”

Section: Introductionmentioning

confidence: 99%

“…Hyperactive hypothalamic–pituitary–adrenal (HPA) axis stress reactivity was accompanied by deficits in social‐like behaviors 34 . This occurred in a sex‐dependent manner in some studies where social‐like behavior is altered in only juvenile males exposed to MIA 35 where other studies demonstrate social deficits in adult male and female offspring 36–38 …”

Section: Introductionmentioning

confidence: 99%

Maternal immune activation with toll‐like receptor 7 agonist during mid‐gestation alters juvenile and adult developmental milestones and behavior

Sheng,

Tobet

2024

J Neuroendocrinology

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Infections during pregnancy are associated with increased risk for adult neuropsychiatric disease, such as major depressive disorder, schizophrenia, and autism spectrum disorder. In mouse models of maternal immune activation (MIA), different toll‐like receptors (TLRs) are stimulated to initiate inflammatory responses in mother and fetus. The goal of this study was to determine sex‐dependent aspects of MIA using a TLR7/8 agonist, Resiquimod (RQ), on neurodevelopment. RQ was administered to timed‐pregnant mice on embryonic day (E) 12.5. At E15, maternal/fetal plasma cytokines were measured by enzyme‐linked immunosorbent assay (ELISA). Maternal cytokines interleukin (IL)‐6 and IL‐10 were higher while tumor necrosis factor (TNF)‐α and IL‐17 were lower in pregnant dams exposed to RQ. Fetal cytokines (E15) were altered at the same timepoint with fetal plasma IL‐6 and IL‐17 greater after RQ compared to vehicle, while IL‐10 and TNF‐α were higher in male fetuses but not female. Other timed‐pregnant dams were allowed to give birth. MIA with RQ did not alter the female to male ratio of offspring born per litter. Body weights were reduced significantly in both sexes at birth, and over the next 5 weeks. Offspring from RQ‐injected mothers opened their eyes 5 days later than controls. Similarly, female offspring from RQ‐injected mothers exhibited pubertal delay based on vaginal opening 2–3 days later than control females. On the behavioral side, juvenile and adult male and female MIA offspring exhibited less social‐like behavior in a social interaction test. Anhedonia‐like behavior was greater in MIA adult female mice. This study provides support for sex‐dependent influences of fetal antecedents for altered brain development and behavioral outputs that could be indicative of increased susceptibility for adult disorders through immune mechanisms. Future studies are needed to determine neural cellular and molecular mechanisms for such programming effects.

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Prenatal and postnatal neuroimmune interactions in neurodevelopmental disorders

Kim,

Huh,

Choi

2024

Nat Immunol

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Maternal immune activation alters social affective behavior and sensitivity to corticotropin releasing factor in male but not female rats

Cited by 4 publications

References 61 publications

Prenatal Fluoxetine Exposure Influences Glucocorticoid Receptor-Mediated Activity in the Prefrontal Cortex of Adolescent Rats Exposed to Acute Stress

Prenatal Fluoxetine Exposure Influences Glucocorticoid Receptor-Mediated Activity in the Prefrontal Cortex of Adolescent Rats Exposed to Acute Stress

Maternal immune activation with toll‐like receptor 7 agonist during mid‐gestation alters juvenile and adult developmental milestones and behavior

Prenatal and postnatal neuroimmune interactions in neurodevelopmental disorders

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