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Proteomic consequences of early postnatal, chronic THC exposure for the adolescent and adult hippocampus

ABSTRACT: This study aims to identify the proteomic targets of THC in the early postnatal hippocampus of developing mice. Therefore, early postnatal C57Bl/6 mice (P5) were exposed daily and for 30 days to plant extracted THC (either 1 mg/kg or 5 mg/kg) or vehicle solution (saline with 3% Tween® 80) for the control group. All animals stayed with their mothers until P25 and after the initial drug exposure time (until P35) animals were given a drug-free resting period. The animals were sacrificed, and their hippocampus was dissected and prepared for the following proteomic analysis at either P48 or after an extended resting period at P120. We found 31 proteins to be changed after THC exposure compared to vehicle at P48 and 186 proteins showing modifications at P120. Gene ontology classification of protein targets revealed a substantial amount of proteins involved in metabolic processes of neurons after THC exposure. The results highlight the vulnerability of the developing hippocampus towards THC exposure and identify the mitochondrial as well as other cell metabolic processes as potential drug targets.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Edit Szodorai

LAB HEAD: Univ. Prof. Dr. Tibor Harkany

PROVIDER: PXD010802 | Pride | 2020-11-09

REPOSITORIES: Pride

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Project description:Background: Prenatal alcohol exposure (PAE) is associated with alterations in numerous physiological systems, including the stress and immune systems. We have previously shown that PAE increases the course and severity of arthritis in an adjuvant-induced arthritis (AA) model. While the molecular mechanisms underlying these effects are not fully known, changes in neural gene expression are emerging as important factors in the etiology of PAE effects. As the prefrontal cortex (PFC) and hippocampus (HPC) play key roles in neuroimmune function, PAE-induced alterations to their transcriptome may underlie abnormal steady-state functions and responses to immune challenge. The current study examined brains from adult PAE and control females from our recent AA study to determine whether PAE causes long-term alterations in gene expression and whether these mediate the altered severity and course of arthritis in PAE females Methods: Adult females from PAE, pair-fed [PF], and ad libitum-fed control [C]) groups were injected with either saline or complete FreundM-bM-^@M-^Ys adjuvant. Animals were terminated at the peak of inflammation or during resolution (days 16 and 39 post-injection, respectively); cohorts of saline-injected PAE, PF and C females were terminated in parallel. Gene expression was analyzed in the PFC and HPC using whole genome mRNA expression microarrays. Results: Significant changes in gene expression in both the PFC and HPC were found in PAE compared to controls in response to ethanol exposure alone (saline-injected females), including genes involved in neurodevelopment, apoptosis, and energy metabolism. Moreover, in response to inflammation (adjuvant-injected females), PAE animals showed unique expression patterns, while failing to exhibit the activation of genes and regulators involved in the immune response observed in control and pair-fed animals. Conclusions: These results support the hypothesis that PAE affects neuroimmune function at the level of gene expression, demonstrating long-term effects of PAE on the CNS response under steady-state conditions and following an inflammatory insult. Key words: prenatal alcohol exposure (PAE), ethanol, inflammation, arthritis, gene expression, rat. 192 samples, including 20 hybridization replicates

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Proteomic consequences of early postnatal, chronic THC exposure for the adolescent and adult hippocampus

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