Gestational THC exposure perturbates hippocampal mitochondrial respiration in the memory-impaired adolescent progeny: Is there a role for mitochondrial CB1 receptor?
Gianluca Lavanco, Valentina Castelli, Cesare D'Amico, Francesca Vaccaro, Giuseppe Tringali, Maria Elisabetta Clementi, Patrizia Bottoni, Martin Kuchař, Petr Palivec, Olivia Engmann, Anna Brancato, Carla Cannizzaro
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie June 2025 DOI: 10.1016/j.biopha.2025.118144 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Offspring of rat dams prenatally exposed to THC or vehicle |
| Dose | 2 mg/Kg |
| Duration | Gestational day 5 to gestational day 20 |
| Measures | Novel Object Recognition test in the L-maze, high-resolution respirometry, ELISA |
| Topics | Cannabis |
| Keywords | Cb1 receptor Complex-i Declarative memory Hippocampus Mitochondria Prenatal THC |
| Key points | Prenatal THC exposure in rats produced significant memory impairment in offspring, along with attenuated hippocampal mitochondrial respiration, reduced complex-I subunit NDUFS1, and increased mitochondrial CB1 receptor expression. The authors propose a functional link between impaired mitochondrial bioenergetics and abnormal CB1 receptor signalling in the hippocampus. |
Abstract
Mitochondria are central to cellular energy metabolism, contributing to synaptic transmission and plasticity. The mitochondrial membranes present the cannabinoid type-1 receptor (mito-CB1R), which has been functionally linked to neuronal energy supply and cognitive processing. Prenatal exposure to Δ9-tetrahydrocannabinol (pTHC) has been associated with cognitive impairments associated with molecular cellular and functional abnormalities in several brain regions, including the hippocampus. This study aims at assessing whether, besides the memory impairment, pTHC exposure may result in mitochondrial molecular and functional alterations in the hippocampus of the offspring. Moreover, the assessment of CB1R expression is also carried out as a proxy of CB1 signalling in pTHC-exposed offspring. THC (2 mg/Kg), or vehicle, was administered to the dams from gestational day (GD) 5 to GD20, and the offspring were tested for declarative memory using the Novel Object Recognition test in the L-maze. We also assessed: mitochondrial respiration by high-resolution respirometry; mitochondrial respiratory complex-I subunit NDUFS1 protein levels, and mito-CB1R expression by ELISA. Our results revealed: significant memory impairment in pTHC-exposed offspring; attenuated mitochondrial respiration in the hippocampus alongside a marked reduction in complex-I-subunit NDUFS1; a significant increase in mito-CB1R expression. This is the first evidence of pTHC exposure-induced impairment in memory processing in the offspring that suggests a functional link between an attenuation in mitochondrial bioenergetics and abnormal CB1R signalling in the hippocampus.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cites 7
- Long-term hippocampal interneuronopathy drives sex-dimorphic spatial memory impairment induced by prenatal THC exposure Neuropsychopharmacology January 26, 2020
- Cannabidiol tempers alcohol intake and neuroendocrine and behavioural correlates in alcohol binge drinking adolescent rats. Focus on calcitonin gene‐related peptide's brain levels Phytotherapy Research July 31, 2023
- Prenatal THC exposure drives sex-specific alterations in spatial memory and hippocampal excitatory/inhibitory balance in adolescent rats. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie December 1, 2024
- CBD enhances the cognitive score of adolescent rats prenatally exposed to THC and fine-tunes relevant effectors of hippocampal plasticity. Frontiers in Pharmacology July 31, 2023
- Prenatal Exposure to Δ9-Tetrahydrocannabinol Affects Hippocampus-Related Cognitive Functions in the Adolescent Rat Offspring: Focus on Specific Markers of Neuroplasticity. Pharmaceutics February 17, 2023
and 2 more in the library