Impact of prenatal THC exposure on mouse brain development; a lifespan approach with MRI

Prenatal cannabis exposure has been demonstrated to impact neurodevelopment in offspring at different ages. To date, to our knowledge, no study has longitudinally examined the effects from embryos to adulthood. Here we collected and analyzed data to explore how prenatal exposure to delta-9-tetrahydrocannabinol (5 mg/kg subcutaneous injections, gestational dat [GD] 3-10) in mice impacts trajectories of brain development with structural magnetic resonance imaging. We supplement these findings with behavioural analyses and electron microscopy as described below.

In the first cohort (embryos) embryos were extracted on GD 17 and scanned with MRI postnatally, as described in the methods of the accompanying paper. Electron microscopy was used to investigate dark neural and glial cells, apoptotic cells, and dividing cells in the hippocampus. In the second cohort (neonates) pups were born and scanned postnatally with manganese enhanced MRI on postnatal day (PND) 3, 5, 7, and 10. Separation-induced ultrasonic vocalizations were acquired on PND 12 and pups were perfused on PND 13. EM analyses were repeated in the neonatal hippocampi. In the third cohort (adults) pups were scanned on PND 25, 35, 60, and 90. Behavioral assessments for anxiety-like behavior with open-field test and sensorimotor gating with prepulse inhibition were performed on PND 35 and 37 respectively. 

Findings showed altered prenatal body volumes and weight-trajectories, altered brain volumes (especially sustained in females until adulthood), and indications of changes to behavior, including anxiety-like phenotypes in neonates and adolescents. Evidence from electron microscopy suggests increased cell division in the embryo hippocampus. Together these data suggest a profound and sustained impact of early gestation prenatal THC exposure on brain development. For further details on the methods, approach, and results, please see the forthcoming publication.

In this dataset you will find the following data:

Pregnancy/dam-level outcomes can be found in maternal_outcomes.zip

zenodo_pregnancy_README.txt: includes description of the data and fields available in each csv.

dam_weights.csv: A spreadsheet including the information related to each dam pooled across the studies

nest_quality.csv: A spreadsheet including the manually-rated nest quality from a pilot and the full experiment

master_maternal_observations_old_thc.csv: A spreadsheet including data for time spent on and off nest extracted automatically and manually from Ethovision

Embryo outcomes:

zenodo_embryos_README.txt: includes description of the data and fields available in each csv.

demographics_for_analysis.csv: A spreadsheet with relevant information for each embryo sample.

raw_embryo_mincs.zip: includes 84 embryo scans, full body

embryo_heads.zip: includes 57 embryo scans that all passed qc, head only niftis 

squish_qc.csv: QC of whether the embryos were squished or not

em_embryo_hc_mm2csv.csv: cells per mm^2 from electron microscopy

Neonate outcomes:

zenodo_neonates_README.txt: includes description of data and fields available in each csv

demographics.csv: A spreadsheet with the demographic information for each pup and timepoint in the study

raw_neonate_niftis.zip: 172 scans from neonates in nifti format

agreement_qc.csv: quality control file with assessments of raw images

milestones_999_as_NA.csv: Record of which milestones were tested and whether they were obtained

master_usv.csv: Spreadsheet including data for ultrasonic vocalizations from all tested pups

neo_cell_counts_mm2.csv: cells per mm^2 from electron microscopy for the neonates

Adult outcomes: 

zenodo_adult_README.txt: includes description of the data and fields available in each csv.

demographics.csv: A spreadsheet with the demographic information for each mouse and timepoint in the study

adult_raw_niftis.zip: The raw data (before preprocessing) in nifti format

master_qc.csv: Quality control assessment of the raw images

master_oft.csv: Values for open field test extracted from Ethovision

avg_trials_ppi.csv: Data from prepulse inhibition trials, average startle of 100 ms following pulse

max_trials_ppi.csv Dat afrom prepulse inhibition trials, maximum startle of 100 ms following pulse