Although brain serotonin levels appear to be unaltered in R e l n +/? mice, both R e l n +/+ and R e l n +/? mice show an increase in brain serotonin levels upon early maternal separation of the pups . clustering into specific membrane domains is known to be of importance for membrane proteins functional regulation: the clustering of neurotransmitter receptors into postsynaptic active sites, the formation of the immunological synapse, the partitioning of membrane proteins into lipid raft domains, and the clustering of membrane proteins to be internalized are good examples of that. The serotonin transporter (SERT) belongs to the SLC6 family of sodium- and chloride-dependent integral membrane proteins, and is the primary responsible for the recapture of released serotonin from the extracellular space [1, 2]. The clustering of SERT into specific membrane domains such as lipid rafts Pindolol , SERT oligomerization [4, 5], and SERT subcellular distribution  appears to be critical for serotonin reuptake activity. SERT is one of the main targets of antidepressant medication, and alterations in SERT expression and activity have been found both in mood and psychotic disorders. In fact, a decrease in SERT binding in blood platelets Pindolol is Pindolol one of the best-characterized biomarkers of depression , and a similar decrease has also been found in peripheral lymphocytes in depression [8C10]. Reelin is a large extracellular matrix protein abundant in brain tissue whose levels are down-regulated in several psychiatric disorders [11C15]. Reelin is also expressed in blood plasma , and alterations in reelin plasma levels are also found in different psychiatric disorders such as schizophrenia, mood disorders, and autism [14, 17], although an accurate measurement of reelin plasma levels is not easily accomplished due to its sensitivity to proteolysis and freeze-thawing cycles . The primary actions of reelin in the nervous systems are regulating neural migration and synaptogenesis in cortical areas during brain development (i.e., cerebral cortex, hippocampus, olfactory bulb, and cerebellum), and later in stabilizing synaptic contacts onto dendritic spines in the adult brain thereby regulating synaptic plasticity (see [19C21]). These actions are mediated at the molecular level by the interaction of reelin with ApoER2-VLDLR receptors, and bring about the phosphorylation of the adaptor protein DAB1 and activation of nonreceptor tyrosine kinases (see as reviews [20, 21]). In addition, reelin also binds integrin receptors resulting in the upregulation of specific mRNAs translation in dendritic spines , Rabbit Polyclonal to YB1 (phospho-Ser102) and an increase in number and clustering of intramembrane particles (i.e., transmembrane proteins) in postsynaptic membrane domains . While reelin actions in the nervous system are well studied, there is not so much knowledge about the possible actions of reelin in blood plasma, although it is known that reelin plasma is mostly secreted by hepatocytes , and is processed by plasminogen activator and plasmin . Homozygous reeler mice (< .05. 3. Results SERT immunolabelling is mostly evidenced as immunofluorescent clusters observed primarily in the lymphocytes plasma membrane (Figures 1(a), 1(c), and 1(e)). Open in a separate window Figure 1 Confocal micrographs (a, c, e) and surface plot graphs (b, d, f) of examples of blood lymphocytes from wild-type (< .05. a, b, d. Different than in R e l n +/+ and R e l n ?/? mice. c, e. Different than in R e l n +/+ and R e l n +/? mice. The average size of SERT immunopositive clusters is increased about 27% in R e l n +/? mice in comparison to wild-type mice, while in reeler mice (R e l n ?/?), the average size of SERT clusters more than doubles that of wild-type mice (and increase of 109%), and is about 64% larger than in heterozygous reeler mice (R e l n +/? (Figure 2(b) and Table 1). The percentage of the lymphocytes surface occupied by SERT immunopositive clusters is also increased in both Pindolol R e l n +/? mice (a 50% increase) and R e l n ?/? mice (an increase of 119%) with respect to wild-type mice (Figure 2(c) and Table 1). In addition, there is an increase of about 47% in the same value in R e l n ?/?mice in comparison with R e l n +/? mice (Figure 2(c) and Table 1). The graphic representation of the distribution of SERT clusters size in lymphocytes evidences that about 60% of the clusters are comprised in the interval of 0.05C0.1?m2 in wild-type R e l n +/+ mice, while this percentage is only of about 40%.