Cross-generational THC exposure alters the developmental sensitivity of ventral and dorsal striatal gene expression in male and female offspring.
- Authors
- Szutorisz, Henrietta; EgervΓ‘ri, Gabor; Sperry, James; Carter, Jenna M; Hurd, Yasmin L
- Year
- 2016
- Journal
- Neurotoxicology and teratology
- PMID
- 27221226
- DOI
- 10.1016/j.ntt.2016.05.005
- PMCID
- PMC5118190
Cannabis (Cannabis sativa, Cannabis indica) is the illicit drug most frequently abused by young men and women. The growing use of the drug has raised attention not only on the impact of direct exposure on the developing brain and behavior later in life, but also on potential cross-generational consequences. Our previous work demonstrated that adolescent exposure to Ξ-tetrahydrocannabinol (THC), the main psychoactive component of cannabis, affects reward-related behavior and striatal gene expression in male offspring that were unexposed to the drug during their own lifespan. The significant sex differences documented for most addiction and psychiatric disorders suggest that understanding the perturbation of the brain in the two sexes due to cannabis could provide insights about neuronal systems underpinning vulnerability to psychiatric illnesses. In the current study, we expanded our previous observations in males by analyzing the female brain for specific aberrations associated with cross-generational THC exposure. Based on the impact of adolescent development on subsequent adult behavioral pathology, we examined molecular patterns during both adolescence and adulthood. The results revealed a switch from the ventral striatum during adolescence to the dorsal striatum in adulthood in alterations of gene expression related to synaptic plasticity in both sexes. Females, however, exhibited stronger correlation patterns between genes and also showed locomotor disturbances not evident in males. Overall, the findings demonstrate cross-generational consequences of parental THC exposure in both male and female offspring.
Schematic overview of the experimental approach used to study the cross-generational effects of parental germline THC exposure in F1 offspring. For details, see Materials and Methods.
Relationships between the mRNA levels of synaptic regulators within striatal subregions and sexes. Correlation analysis of the mRNA levels measured by qRT-PCR in samples combining offspring with parental THC or VEH exposure. (A, C) Adult F1 males. (B, D) Adult F1 females. Colors in heat maps represent Pearson correlation coefficient (r) values. Scatter plots show the distribution of mRNA levels between animal subjects. N= 16 (8 males+8 females)/treatment group. VS, ventral striatum; DS, dorsal striatum.
Parental THC exposure alters the relationships between the mRNA levels of synaptic regulators in the dorsal striatum. Correlation analysis of the mRNA levels measured by qRT-PCR. (A, C) Germline VEH- and THC-exposed adult F1 males, respectively. (B, D) Germline VEH- and THC-exposed adult F1 females, respectively. Colors in heat maps represent Pearson correlation coefficient (r) values. Scatter plots show the distribution of mRNA levels between animal subjects. N=8/ treatment/sex. DS, dorsal striatum.
Parental germline THC exposure leads to decreased novelty-related locomotor activity in adult F1 females. Open field horizontal activity in adult F1 male (A) and female (B) offspring. N=10-12 animals/group. Values are expressed as a mean Β± SEM. * indicates p< 0.05 vs control (F1-VEH) subjects.
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