Overabundant endocannabinoids in neurons are detrimental to cognitive function
Zhu, D.; Zhang, J.; Ma, X.; Hu, M.; Gao, F.; Hashem, J.; Lyu, J.; Wei, J.; Cui, Y.; Qiu, S.; Chen, C.
Show abstract
2-Arachidonoylglycerol (2-AG) is the most prevalent endocannabinoid involved in maintaining brain homeostasis. Previous studies have demonstrated that inactivating monoacylglycerol lipase (MAGL), the primary enzyme responsible for degrading 2-AG in the brain, alleviates neuropathology and prevents synaptic and cognitive decline in animal models of neurodegenerative diseases. However, we show that selectively inhibiting 2-AG metabolism in neurons impairs cognitive function in mice. This cognitive impairment appears to result from decreased expression of synaptic proteins and synapse numbers, impaired long-term synaptic plasticity and cortical circuit functional connectivity, and diminished neurogenesis. Interestingly, the synaptic and cognitive deficits induced by neuronal MAGL inactivation can be counterbalanced by inhibiting astrocytic 2-AG metabolism. Transcriptomic analyses reveal that inhibiting neuronal 2-AG degradation leads to widespread changes in expression of genes associated with synaptic function. These findings suggest that crosstalk in 2-AG signaling between astrocytes and neurons is crucial for maintaining synaptic and cognitive functions and that excessive 2-AG in neurons alone is detrimental to cognitive function.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Aberrant hippocampal transmission and behavior in mice with a stargazin mutation linked to intellectual disability 97%
- Neural stem and progenitor cells support and protect adult hippocampal function via vascular endothelial growth factor secretion. 97%
- Erythropoietin restrains the inhibitory potential of interneurons in the mouse hippocampus 97%
Similar papers in this journal
- Pathway-specific deregulation of striatal excitatory synapses in LRRK2 mutations 96%
- KIF2C regulates synaptic plasticity and cognition by mediating dynamic microtubule invasion of dendritic spines 96%
- PTBP1 Depletion in Mature Astrocytes Reveals Distinct Splicing Alterations Without Neuronal Features 96%
Similar papers in this journal
- Cytoplasmic accumulation of FUS triggers early behavioral alterations linked to cortical neuronal hyperactivity and defects in inhibitory synapses 97%
- Age-dependent regulation of axoglial interactions and behavior by oligodendrocyte AnkyrinG 97%
- Abnormal AMPAR-mediated synaptic plasticity, cognitive and autistic-like behaviors in a missense Fmr1 mutant mouse model of Fragile X syndrome 96%
Similar papers in this journal
- Protein lactylation induced by neural excitation 96%
- Loss-of-function variants in the schizophrenia risk gene SETD1A alter neuronal network activity in human neurons through cAMP/PKA pathway 96%
- Jedi-1/MEGF12-mediated phagocytosis controls the pro-neurogenic properties of microglia in the ventricular-subventricular zone 96%
Similar papers in this journal
- Enhanced FGFR3 activity in post-mitotic principal neurons during brain development results in cortical dysplasia and axon miswiring 97%
- Regulation of Glypican 6-mediated Wnt activation maintains TDP-43 nuclear localization in neurons 96%
- Pyk2 in dorsal hippocampus plays a selective role in spatial memory and synaptic plasticity 96%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.