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Novel Insights into Changes in Gene Expression within the Hypothalamus in Two Asthma Mouse Models: A Transcriptomic
Eslam M Bastawy1, Izel M Eraslan1, Lara Voglsanger1
1Faculty of Health, School of Medicine, Institute for Mental and Physical Health and Clinical Translation (IMPACT), Deakin University, Geelong 3216, Australia.
International Journal of Molecular Sciences
|July 13, 2024
Summary
Asthma-induced lung inflammation alters gene expression in the mouse hypothalamus, impacting pathways related to neurotransmitter signaling and neuroinflammation. These findings shed light on lung-brain connections and potential therapeutic targets for mental health conditions.
Area of Science:
- Neuroscience
- Immunology
- Genomics
Background:
- Asthma is linked to higher rates of mental illness, but the molecular mechanisms of lung-brain communication are unclear.
- Hypothalamic dysfunction is common in psychiatric disorders, especially those involving inflammation, due to its vulnerability.
- Understanding these connections is crucial for addressing neuropsychiatric sequelae of lung diseases.
Purpose of the Study:
- To investigate gene expression changes in the hypothalamus of mice following induced lung inflammation (asthma).
- To identify molecular pathways linking lung inflammation to potential brain dysfunction.
- To explore potential therapeutic targets for asthma-related mental health issues.
Main Methods:
- Induced lung inflammation in BALB/c mice using lipopolysaccharide (LPS) or ovalbumin (OVA) allergens.
- Confirmed lung inflammation via histological examination of lung tissue.
- Micro-dissected the hypothalamus, extracted RNA, and performed RNA transcriptome profiling (sequencing).
Main Results:
- LPS exposure significantly altered the expression of 31 single genes in the hypothalamus (FDR < 5%).
- Ovalbumin (OVA) treatment showed no significant single gene changes, indicating a milder hypothalamic response.
- Gene set analysis revealed 48 upregulated and 8 downregulated gene sets in both asthma groups, involved in immune response, metabolism, and neuroplasticity, including five related to neurotransmitter signaling.
Conclusions:
- Lung inflammation associated with asthma can induce molecular changes in the hypothalamus.
- Altered gene sets in the hypothalamus are linked to neurotransmitter signaling, neuroinflammation, and potentially mental health.
- These findings provide insights into lung-brain crosstalk and identify pathways for future therapeutic interventions.
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