ArticleTranslational psychiatry2022
Short-term exposure to an obesogenic diet during adolescence elicits anxiety-related behavior and neuroinflammation: modulatory effects of exogenous neuregulin-1.
Article in Translational psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 17 citations in OpenAlex.
- Forsythoside A attenuates metabolic dysfunction in type 2 diabetic mice by inhibiting the MAPK and activating the Nrf2 signalling pathways.Arhiv za higijenu rada i toksikologiju · 2026Article
- Impact of adolescent high-fat diet and psychosocial stress on neuroendocrine stress responses and binge eating behavior in adult male Lewis rats.Hormones and behavior · 2025Article
- Growth hormone reduces retinal inflammation and preserves microglial morphology after optic nerve crush in male rats.Frontiers in cellular neuroscience · 2025Article
- Early-life obesogenic environment integrates immunometabolic and epigenetic signatures governing neuroinflammation.Brain, behavior, & immunity - health · 2024Article
- Physiopathological Roles of White Adiposity and Gut Functions in Neuroinflammation.International journal of molecular sciences · 2024Review
- Role of the prefrontal cortical protease TACE/ADAM17 in neurobehavioral responses to chronic stress during adolescence.Brain and behavior · 2024Article
- Hyperfunction of post-synaptic density protein 95 promotes seizure response in early-stage aβ pathology.EMBO reports · 2024Article
- Shifts in naturalistic behaviors induced by early social isolation stress are associated with adult binge-like eating in female rats.Frontiers in behavioral neuroscience · 2024Article
- Obesity-Induced Brain Neuroinflammatory and Mitochondrial Changes.Metabolites · 2023Review
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Childhood obesity leads to hippocampal atrophy and altered cognition. However, the molecular mechanisms underlying these impairments are poorly understood. The neurotrophic factor neuregulin-1 (NRG1) and its cognate ErbB4 receptor play critical roles in hippocampal maturation and function. This study aimed to determine whether exogenous NRG1 administration reduces hippocampal abnormalities and neuroinflammation in rats exposed to an obesogenic Western-like diet (WD). Lewis rats were randomly divided into four groups (12 rats/group): (1) control diet+vehicle (CDV); (2) CD + NRG1 (CDN) (daily intraperitoneal injections: 5 μg/kg/day; between postnatal day, PND 21-PND 41); (3) WD + VEH (WDV); (4) WD + NRG1 (WDN). Neurobehavioral assessments were performed at PND 43-49. Brains were harvested for MRI and molecular analyses at PND 49. We found that NRG1 administration reduced hippocampal volume (7%) and attenuated hippocampal-dependent cued fear conditioning in CD rats (56%). NRG1 administration reduced PSD-95 protein expression (30%) and selectively reduced hippocampal cytokine levels (IL-33, GM-CSF, CCL-2, IFN-γ) while significantly impacting microglia morphology (increased span ratio and reduced circularity). WD rats exhibited reduced right hippocampal volume (7%), altered microglia morphology (reduced density and increased lacunarity), and increased levels of cytokines implicated in neuroinflammation (IL-1α, TNF-α, IL-6). Notably, NRG1 synergized with the WD to increase hippocampal ErbB4 phosphorylation and the tumor necrosis alpha converting enzyme (TACE/ADAM17) protein levels. Although the results did not provide sufficient evidence to conclude that exogenous NRG1 administration is beneficial to alleviate obesity-related outcomes in adolescent rats, we identified a potential novel interaction between obesogenic diet exposure and TACE/ADAM17-NRG1-ErbB4 signaling during hippocampal maturation. Our results indicate that supraoptimal ErbB4 activities may contribute to the abnormal hippocampal structure and cognitive vulnerabilities observed in obese individuals.
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