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Developmental cigarette smoke exposure: hippocampus proteome and metabolome profiles in low birth weight pups
Rachel E Neal1, Jing Chen2, Rekha Jagadapillai3
1Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, KY, USA; Birth Defects Center, University of Louisville, Louisville, KY, USA.
Insights
Developmental exposure to cigarette smoke (CSE) impacts the hippocampus, altering key metabolic and neurodevelopmental pathways. This study reveals molecular changes in the brain from prenatal through early postnatal development.
Area of Science:
- Neuroscience
- Developmental Biology
- Biochemistry
Background:
- Developmental exposure to cigarette smoke (CSE) is associated with neurodevelopmental deficits and cognitive impairments.
- Specific molecular changes in brain regions due to developmental CSE are not well understood.
Purpose of the Study:
- To investigate the biomolecular alterations in the hippocampus following developmental CSE.
- To identify specific molecular and metabolic pathways affected by CSE during critical brain development periods.
Main Methods:
- Utilized a mouse model for 'active' developmental CSE from pre-implantation to postnatal day 21.
- Performed gel-based proteomic and non-targeted metabolomic profiling on hippocampus tissue.
- Employed partial least squares-discriminant analysis (PLS-DA) and Ingenuity Pathway Analysis (IPA) for data interpretation.
Main Results:
- CSE significantly altered pathways related to glycolysis and oxidative phosphorylation in the hippocampus.
- Detected impacts on fatty acid metabolism and neurodevelopmental pathways.
- Identified specific molecular and metabolic features of interest through PLS-DA.
Conclusions:
- Developmental CSE induces significant molecular and metabolic changes in the hippocampus.
- These alterations affect fundamental cellular processes including energy metabolism and neurodevelopment.
- The findings provide insight into the neurobiological mechanisms underlying CSE-induced cognitive deficits.
Abstract:
Exposure to cigarette smoke during development is linked to neurodevelopmental delays and cognitive impairment including impulsivity, attention deficit disorder, and lower IQ. However, brain region specific biomolecular alterations induced by developmental cigarette smoke exposure (CSE) remain largely unexplored. In the current molecular phenotyping study, a mouse model of 'active' developmental CSE (serum cotinine > 50 ng/mL) spanning pre-implantation through third trimester-equivalent brain development (gestational day (GD) 1 through postnatal day (PD) 21) was utilized. Hippocampus tissue collected at the time of cessation of exposure was processed for gel-based proteomic and non-targeted metabolomic profiling with partial least squares-discriminant analysis (PLS-DA) for selection of features of interest. Ingenuity pathway analysis was utilized to identify candidate molecular and metabolic pathways impacted within the hippocampus. CSE impacted glycolysis, oxidative phosphorylation, fatty acid metabolism, and neurodevelopment pathways within the developing hippocampus.
