Abstract
The field of cannabinoid research has been receiving ever-growing interest. Ongoing debates worldwide about the legislation of medical cannabis further motivates research into cannabinoid function within the central nervous system (CNS). To date, two well-characterized cannabinoid receptors exist. While most research has investigated Cb1 receptors (Cb1Rs), Cb2 receptors (Cb2Rs) in the brain have started to attract considerable interest in recent years. With indisputable evidence showing the wide-distribution of Cb2Rs in the brain of different species, they are no longer considered just peripheral receptors. However, in contrast to Cb1Rs, the functionality of central Cb2Rs remains largely unexplored. Here we review recent studies on hippocampal Cb2Rs. While conflicting results about their function have been reported, we have made significant progress in understanding the involvement of Cb2Rs in modulating cellular properties and network excitability. Moreover, Cb2Rs have been shown to be expressed in different subregions of the hippocampus, challenging our prior understanding of the endocannabinoid system. Although more insight into their functional roles is necessary, we propose that targeting hippocampal Cb2Rs may offer novel therapies for diseases related to memory and adult neurogenesis deficits.
Highlights
Peripheral Cb2 receptors – a half-truth AbstractThe field of cannabinoid research has been receiving ever-growing interest
More insight into their functional roles is necessary, we propose that targeting hippocampal Cb2 receptors (Cb2Rs) may offer novel therapies for diseases related to memory and adult neurogenesis deficits
A follow-up study showed that knocking out the Cb2R gene decreases hippocampal excitatory synaptic transmission, long-term potentiation, and dendritic spine density, indicating that the endogenous activity of Cb2R contributes to the maintenance of synaptic function and regulates cognitive functions such as long-term memory (Li and Kim 2016b). These results suggest that the loss of Cb2R may lead to hippocam pal-dependent memory deficits, though they should be interpreted with caution since compensatory mechanisms may occur in developmental knockout mice
Summary
COX-2, TNF-α, IL-1β nNOS, iNOS Microglial activation p38 NF-κB activation (MAPK pathway) Nitric Oxide Caspase 3 activation. Microglial Cb2R expression in mouse and rat hippocampi was first demonstrated using different Cb2R-specific antibodies (Brusco et al 2008; Gong et al 2006). More recent studies challenge some of the results previously shown by Onaivi and colleagues. Some publications challenge the specificity of Cb2R antibodies, and overall results indicate that currently available antibodies may lack specificity and may lead to conflicting outcomes (Li and Kim 2015). Considering these results, more validating research needs to be conducted. Summary of Cb2R expression studies in the hippocampus so sp sr CA1 suggests that the notion of the ECS as a retrograde signaling system might not be complete (Castillo et al 2012). The postsynaptic localization of Cb2Rs in principal cells reveals a more complex role for the ECS in the hippocampus than previously thought
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