Adult Rat Offspring Exposed to THC during Gestation Exhibit Distinct Biomolecular Changes Identified by X-ray Fluorescence Imaging and Fourier Transform Infrared Spectroscopy in Cortico-Limbic Circuits

Perspectives surrounding Cannabis use have transformed over the past decade. This shift in perspective has been noted in pregnant populations in Canada and the US, where various investigations report that the use of Cannabis in pregnancy is increasingly commonplace. There is some evidence indicating that Δ9-tetrahydrocannabinol (THC), the main intoxicating phytocannabinoid found within Cannabis flower, may influence the biochemical composition of lipids within the developing fetal brain. The aim of this study was to apply multimodal biospectroscopic imaging techniques, X-ray fluorescence imaging (XFI) and Fourier transform mid-infrared spectromicroscopy (FTIR), to investigate the biochemical and biomolecular changes underlying the distinct behavioral phenotypes identified previously. XFI was used to investigate the presence of metal, nonmetal, and alkali dysregulation, while FTIR provided information on neurochemical dysbiosis within the brains of offspring exposed to THC (3 mg/kg; i.p.) or vehicle (VEH). The THC offspring exhibited decreased copper (Cu) concentrations within the perimeter of their corpus callosum, as identified by XFI. FTIR hyperspectral data from the brain revealed noteworthy changes in peaks associated with lipid methylene (CH2as), carbohydrates, and peak ratios identifying changes in the lipid structure and the relative content of lipids, cholesterol esters, and cholesterols to saturated fatty acids. These changes were particularly evident in the hippocampus, where THC offspring exhibited increased CH2as, lipid esters, phosphate, protein, and unsaturation levels of lipids. The biochemical changes seen in the FTIR spectra were modest, with THC offspring showing an increase in the number of structural changes of lipids in the corpus callosum and an increase in protein in the lateral ventricle. This study supports the usefulness of these techniques to detect subtle changes in biomolecular composition within brain tissues exposed to gestational THC. These results contribute to the growing body of knowledge unraveling the complex effects of THC on fetal neurodevelopmental trajectories.