This is comparable to lysosomal enzymes having activity in the foci of inflammation [49,50,51]

This is comparable to lysosomal enzymes having activity in the foci of inflammation [49,50,51]. == 1. Introduction == The prevalence of bipolar affective disorder (BD) is about 1% in the general population [1] and has remained consistently high over the past 30 years [2]. Bipolar affective disorder is a chronic disorder of mood that is characterized by a combination of manic, hypomanic and depressive episodes, which are expressed as recurrent cases of changes in energy levels and behavior [3]. It can be subdivided into bipolar disorder I (BD I), defined by the occurrence of at least one lifetime manic or mixed affective episode along with and recurrent depressive episodes and bipolar disorder II (BD II), defined by the occurrence of at least one hypomanic episode and one major depressive episode [4]. This disorder is associated with high rates of premature mortality from medical comorbidities and suicide [5]. However, the etiology and mechanisms underlying bipolar disorder are not well understood. Numerous diffusion tensor imaging studies [6], genome-wide association studies [7,8], and postmortem studies [9,10] have demonstrated a reduction in myelin content in the CNS, aberrant expression of myelin-related genes and damage of oligodendrocytes, Metanicotine along with decreased myelin staining in BD patients. A recent meta-analysis involving 32 studies confirms a reduction in fractional anisotropy and an increase in radial diffusivity in individuals with BD compared to healthy subjects, supporting the hypothesis of alterations in myelination as a possible mechanism of BD [6]. Myelination in BD might change after affective episodes [11], accompanied by altered activity levels or cognitive biases associated with depression and mania [12]. Additionally, a global age-related deficit in intracortical myelin maturation throughout the cortex has been identified in bipolar disorder, which the authors of the study attribute to potential cognitive and behavioral impairments [13]. One of the main protein components of myelin in the human CNS is myelin basic protein (MBP), which may enter the cerebrospinal fluid or bloodstream and have highly Rabbit Polyclonal to BL-CAM (phospho-Tyr807) immunogenic properties [14]. MBP is responsible for the adhesion of myelin sheaths of oligodendrocytes, may participate in signaling in the nucleus, in interactions with the cytoskeleton, and a regulatory function in the expression of other myelin proteins [15]. Antibodies to MBP appear in violation of the integrity of myelin during stroke [16], brain injury Metanicotine [17], multiple sclerosis [18], systemic lupus erythematosus [19], autism [20], and schizophrenia [21]. It is suggested that immune system dysfunction and inflammatory processes may influence myelination abnormalities in various psychiatric disorders, including BD [22,23,24]. The integrity and permeability of the bloodbrain barrier change during pro-inflammatory conditions during bipolar depression [25]. Recent studies have shown that bipolar disorder involves Metanicotine microglial activation in the hippocampus and alterations in peripheral cytokines, suggesting a potential link between neuroinflammation and peripheral toxicity [24,26]. There is evidence of a reduced number of circulating T-regulatory lymphocytes, which suppress hyperactive immune responses and the development of autoimmune diseases [24,26], and their correlations with brain white matter integrity in patients with BD [22,23]. Furthermore, recent works have thoroughly supported the association between BD and a proinflammatory state, involving both the innate and the adaptive immune system. In particular, they revealed an increase in the production of IL-4, IL-5, and IL-10 suggests Th2 cells activation and enhanced antibody-mediated reactions [13]. A wide range of autoantibodies were identified in BD, including a group of antinuclear and antiphospholipid autoantibodies, antibeta2-glycoprotein, anti-tissue transglutaminase IgA [27], and anti-thyroid peroxidase antibodies [28]. In addition, autoantibodies to neuro-specific antigens, such as IgM to NMDA receptors, have been found in cases of bipolar affective disorder and psychosis [29,30], including the early stages of the disease [30]. It is reasonable to assume that among such a wide range Metanicotine of antibodies in BD, antibodies with catalytic activity may also appear. Over recent decades, the catalytic properties of antibodies have been demonstrated, which allow them not only to bind but also to hydrolyze.