Exposure to Δ9-tetrahydrocannabinol leads to a rise in caspase-3, morphological changes in microglial, and astrocyte reactivity in the cerebellum of rats.

The present study aimed to elucidate the effect of 10 mg/kg Δ9-tetrahydrocannabinol (THC) on cerebellar neuronal and glial morphology, apoptosis and inflammatory gene expression using a series of histological assays including stereology, Sholl analysis, immunofluorescence and real-time qPCR in male Wistar rats. A decrease in the number of Purkinje neurons and the thickness of the granular layer in the cerebellum was reported in THC-treated rats. Increased expression of Iba-1 and arborization of microglial processes were evidence of microgliosis and morphological changes in microglia. In addition, astrogliosis and changes in astrocyte morphology were other findings associated with THC administration. THC also led to an increase in caspase-3 positive cells and a decrease in autophagy and inflammatory gene expression such as mTOR, BECN1 and LAMP2. However, there were no significant changes in the volume of molecular layers and white matter, the spatial arrangement of granular layers and white matter, or the spatial arrangement of granular layers and white matter in the cerebellum. Taken together, our data showed both neuroprotective and neurodegenerative properties of THC in the cerebellum, which require further study in the future.

The role of Tetrahydrocannabinol in inducing disrupted signaling cascades, hippocampal atrophy and memory defects.

Tetrahydrocannabinol (THC), a major psychoactive constituent of marijuana, can substantially change the function of several brain areas, leading to behavioral impairment including memory and learning dysfunction. Given the importance of hippocampus as one of the chief parts of the brain involved in memory processing, the present study seeks to investigate structural and histological alterations in hippocampus as well as behavioral defects provoked by THC treatment. Besides, using genome-wide sequencing, we adopted a pathway-based approach to discover dysregulated molecular pathways. Our results demonstrated remarkable hippocampal atrophy, and also interrupted memory function and long term potentiation (LTP) under THC exposure. We also detected several dysregulated signaling pathways involved in synaptic plasticity as well as cell-cell interaction in the hippocampus of THC-treated rats. Overall, the results indicate a potential correlation between disrupted signaling cascades, hippocampal atrophy and memory defects caused by THC treatment.