Dataset Information

Cannabinoid receptor 2 deletion influences social memory and synaptic architecture in the hippocampus.

ABSTRACT: Although the cannabinoid receptor 2 (CB₂R) is often thought to play a role mainly outside the brain several publications unequivocally showed the presence of CB₂R on hippocampal principal neurons. Activation of CB₂R produced a long-lasting membrane potential hyperpolarization, altered the input/output function of CA2/3 principal neurons and produced alterations in gamma oscillations. However, other cellular, molecular and behavioral consequences of hippocampal CB₂R signaling have not been studied in detail. Here we demonstrate that the deletion of CB₂ leads to a highly significant increase in hippocampal synapsin-I expression levels and particle density, as well as increased vesicular GABA transporter (vGAT) levels. This phenotype was restricted to females and not observed in males. Furthermore, we demonstrate an impairment of social memory in CB₂ deficient mice. Our results thus demonstrate that the lack of CB₂R leads to changes in the hippocampal synaptic landscape and reveals an important sex-specific difference in endocannabinoid signaling. This study supports a significant role of the CB₂R in modulation of different types of memory despite its low expression levels in the brain and provides more insight into a sex-specific role of CB₂R in synaptic architecture.

SUBMITTER: Komorowska-Muller JA

PROVIDER: S-EPMC8376893 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Cannabinoid receptor 2 deletion influences social memory and synaptic architecture in the hippocampus.

Komorowska-Müller Joanna Agnieszka JA Ravichandran Kishore Aravind KA Zimmer Andreas A Schürmann Britta B

Scientific reports 20210819 1

Although the cannabinoid receptor 2 (CB2R) is often thought to play a role mainly outside the brain several publications unequivocally showed the presence of CB2R on hippocampal principal neurons. Activation of CB2R produced a long-lasting membrane potential hyperpolarization, altered the input/output function of CA2/3 principal neurons and produced alterations in gamma oscillations. However, other cellular, molecular and behavioral consequences of hippocampal CB ...[more]

PMID: 34413398

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Project description:Aging is a process characterized by cognitive impairment and mitochondrial dysfunction. In neurons, these organelles are classified as synaptic and non-synaptic mitochondria depending on their localization. Interestingly, synaptic mitochondria from the cerebral cortex accumulate more damage and are more sensitive to swelling than non-synaptic mitochondria. The hippocampus is fundamental for learning and memory, synaptic processes with high energy demand. However, it is unknown if functional differences are found in synaptic and non-synaptic hippocampal mitochondria; and whether this could contribute to memory loss during aging. In this study, we used 3, 6, 12 and 18 month-old (mo) mice to evaluate hippocampal memory and the function of both synaptic and non-synaptic mitochondria. Our results indicate that recognition memory is impaired from 12mo, whereas spatial memory is impaired at 18mo. This was accompanied by a differential function of synaptic and non-synaptic mitochondria. Interestingly, we observed premature dysfunction of synaptic mitochondria at 12mo, indicated by increased ROS generation, reduced ATP production and higher sensitivity to calcium overload, an effect that is not observed in non-synaptic mitochondria. In addition, at 18mo both mitochondrial populations showed bioenergetic defects, but synaptic mitochondria were prone to swelling than non-synaptic mitochondria. Finally, we treated 2, 11, and 17mo mice with MitoQ or Curcumin (Cc) for 5 weeks, to determine if the prevention of synaptic mitochondrial dysfunction could attenuate memory loss. Our results indicate that reducing synaptic mitochondrial dysfunction is sufficient to decrease age-associated cognitive impairment. In conclusion, our results indicate that age-related alterations in ATP produced by synaptic mitochondria are correlated with decreases in spatial and object recognition memory and propose that the maintenance of functional synaptic mitochondria is critical to prevent memory loss during aging.

Dataset Information

Cannabinoid receptor 2 deletion influences social memory and synaptic architecture in the hippocampus.

Publications

Cannabinoid receptor 2 deletion influences social memory and synaptic architecture in the hippocampus.

Similar Datasets

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