• Pumilio
• Endocannabinoid system
• CB2
• Staufen
• Bipolar disorder

Genetic association between bipolar disorder and 524A>C (Leu133Ile) polymorphism of CNR2gene, encoding for CB2 cannabinoid receptor (abstract).

Bipolar Disorder, an illness that affects an estimated 2.3 million American adults, has been characterized in many different ways. The original diagnosis of ―manic-depressive insanity,‖ described by Emil Kraepelin in the 1899 edition of Clinical Psychiatry, has evolved through the years to the current classification system of four subtypes: Bipolar I Disorder, Bipolar II Disorder, Cyclothymic Disorder and Bipolar Disorder Not Otherwise Specified. The primary mood disturbance in Bipolar I Disorder is either mania or a mixed episode and it is usually accompanied by episodes of depression while the primary mood disturbance in Bipolar II disorder is depression and it is accompanied by at least one episode of a mild form of mania called hypomania. Instead, an individual with Cyclothymic Disorder cycles between periods of hypomanic symptoms and periods of depressive Symptoms. The hypomanic symptoms are never severe enough to be considered a manic episode and the depressive symptoms are never severe enough to be considered a depressive episode. BD Not Otherwise Specified captures all of the other variants of the disease that do not fit nearly into one of the above categories.
The etiology of BD is very complex. A lot of various biological system are involved in neurobiology of this disorder impairing function or just changing in morphology.
The best characterized neurotransmitter systems involved in pathophysiology of BD are dopaminergic and serotononinergic, but also GABAergic and glutamatergic (Manji et al., 2003).
More recently also the ECS has been identified as an important target of several psychiatric disorders including the bipolar one.
In the past a lot of studies have investigated more the role of CBR1 in CNS than CBR2 because the expression of this latter receptor was considered only at microglia levels; recently the discovery of mRNA of the isoforms CBR2A in very important regions of human brain such as caudate, amygdale, hippocampus, cerebellum, nucleus accumbens, putamen and cortex (Liu et al., 2009) could permit to understand better the role of CBR2 not only in nuroinflammation process but also in neurotransmission and so also in depression and related disorders, as is BD.
Then, the important role of CBR2 as mediator of PIM and the evidences that a lot of bipolar patients suffer of obesity, insulin resistance, arthritis, pain and cardiovascular illness, all pathologies correlated to alteration of CBR2, suggest that this CBR could really interfere with the pathology of BD.
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So, in this study we tested the hypothesis that genetic variants of CNR2 might be associated with BD. In particular, by means of a case–control study the frequencies of three missense SNPs of CNR2, namely rs2501432 (315A>G; Arg63Gln), rs41311993 (524C>A; Leu133Ile) and rs2229579 (1073C>T; Tyr316His) (Fig.12) have been assessed in a sample of 80 BD patients and 160 healthy control.The comparison between patients and healthy group shows that allele frequencies were significantly different for CNR2 524C>A (p(χ2) =0.001) while there was no significant difference for CNR2 315A>G (p(χ2) =0.15) or1073C>T (p(χ2) =0.21).
The CNR2 524C>A substitution leads to the aminoacid change Leu133Ile which has been suggested to influence the stability and/or functionality of the CBR2. In fact, Leu133 provides a hydrophobic residue involved in an intrachain bond in the transmembrane domains and its presence is thought to be crucial for the stability of the receptor and may influence the receptor-G protein coupling (Xie et al., 2003).

Interaction between Pum2 and Stau1 RNA-binding proteins and their role in behavior (abstract).

Many large or morphologically complex cells compartmentalize information by targeting either mRNAs or proteins to specific domains and maintain the localization of these molecules over time. These distinct cellular domains can function to determine cell polarity, define embryonic axes, or contribute to cellular memory. Although much is understood about how proteins move and are targeted in cells, our understanding of the mechanisms of RNA transport and localization are at an early stage. In neurobiology, the importance of these mechanisms for synaptic plasticity has recently become apparent. In this study, I have focused my attention on two RNA-binding proteins that are associated with impairments in learning and memory, in dendritic spine morphogenesis and in other aspects involved in synaptic plasticity: Stau1 and Pum2. Since the Stau/Pum pathway has been shown to be involved in long-term memory in Drosophila by Dubnau and colleagues, these two genes appear fundamental for memory formation (Dubnau et al., 2003). I have investigated how a gene trap mutation in one of these two genes could interfere with the expression of the other protein and which kind of effects these alteration could have in behavior features as response to a new environment and condition. Using transgenic mice for both proteins, Stau1tm1Apa and Pum2XE77 mice, I have shown that a gene trap mutation in one of these RNA-binding proteins changes not only the level of the disrupted protein, but also of the other one indicating a link between Stau1 and Pum2. To better understand these data I conducted behavioral tests for Stau1tm1Apa and Pum2XE77 mice analyzing several parameters to identify common and different features in behavior between the two transgenic mice groups.
Our results are still preliminary and further studies, extending the sample number and the type of behavior test will be conducted in the future to validate the results presented here. Regardless, these results led me to conclude that the Stau/Pum pathway should be better investigated for its role in memory processes including the mechanism, which regulate the expression levels of these two proteins.