Al GM compartment occurred until the age of 5, CPI-203 site followed by a steady decline in volume throughout the remaining lifespan. In a 5-year MRI follow-up study, however, Van Haren et al. [4] assessed 113 participants, and observed essentially no decrease until the age of 30 years. From that age onward, cerebral volume gradually decreased. Furthermore, studies of healthy volunteers reported significant trends in age-related volume reduction in certain regions of the brain, including the hippocampus [5], the cerebellum [1], and the prefrontal [2], temporal [2], and occipital lobes [5].Twin studies have shown that many aspects of brain structure are highly heritable, with heritability estimates ranging from 82 for gray matter to 88 for white matter [6,7]. A longitudinal study of 71 twin pairs by Prefferbaum et al. [11] showed that genetic contributions to variability in brain structure were high at baseline and at a 4-year follow-up. Although the genetic components of age-related changes in the human brain volume remain largely unknown, several candidate genes have been suggested to influence age-related changes in brain structure. Sublette et al. [8] reported that an allelic variant of brain-derived neurotrophic factor (BDNF) was associated with age-related changes in the amygdala volume, and Nemoto et al. [9] reported that the same BDNF allelic variant influenced age-related changes in brain morphology. The apolipoprotein E genotype has also been shown to have an impact on age-related GM volume loss [10]. The findings of these studies suggest that genetic variation may influence age-related changes in brain morphology. The anti-apoptotic protein B-cell CLL/lymphoma 2 (Bcl-2) is a major inhibitor of apoptotic and necrotic cell death [12]. Bcl-2 also plays critical roles in neuronal morphogenesis and synapticBcl-2 and Age-Related Gray Matter Volume Changesplasticity [13,14], and altered Bcl-2 function has been proposed to contribute to the impairment of cellular plasticity and resilience in neuropsychiatric patients [12]. Bcl-2 may support central neurons through intracellular calcium signaling, which stimulates the regenerative response and neuronal differentiation [15], and this mechanism may influence aging processes 15857111 and pathogenesis in neurodegenerative disease [16]. These findings collectively suggest that Bcl-2 may play a critical role in the modulation of aging processes in the brain [17,18]. Uemura et al. [19] recently demonstrated that the intronic single nucleotide polymorphism (SNP) Bcl-2 rs956572 influences Bcl-2 function in B lymphoblast cell lines derived from bipolar disorder patients. The levels of Bcl-2 mRNA and protein were lowest in cell lines of patients with the G/G genotype, compared to that of patients with the other functional genotypes, G/A and A/ A. In CUDC-907 custom synthesis contrast, an earlier study using similar cell lines found that the A/A genotype was associated with significantly lower Bcl-2 expression and greater cellular sensitivity to stress-induced apoptosis, compared with the G/G genotype [20]. However, both studies showed that the Bcl-2 polymorphism was associated with intracellular calcium homeostasis in lymphoblast cells derived from bipolar disorder patients. A growing body of evidence indicates that a relationship exists between altered Bcl-2 expression and the neurodegenerative process [18], and that calcium signaling is responsible for neuronal aging and degeneration [21]. Increased vulnerability to Bcl-2related apoptosis.Al GM compartment occurred until the age of 5, followed by a steady decline in volume throughout the remaining lifespan. In a 5-year MRI follow-up study, however, Van Haren et al. [4] assessed 113 participants, and observed essentially no decrease until the age of 30 years. From that age onward, cerebral volume gradually decreased. Furthermore, studies of healthy volunteers reported significant trends in age-related volume reduction in certain regions of the brain, including the hippocampus [5], the cerebellum [1], and the prefrontal [2], temporal [2], and occipital lobes [5].Twin studies have shown that many aspects of brain structure are highly heritable, with heritability estimates ranging from 82 for gray matter to 88 for white matter [6,7]. A longitudinal study of 71 twin pairs by Prefferbaum et al. [11] showed that genetic contributions to variability in brain structure were high at baseline and at a 4-year follow-up. Although the genetic components of age-related changes in the human brain volume remain largely unknown, several candidate genes have been suggested to influence age-related changes in brain structure. Sublette et al. [8] reported that an allelic variant of brain-derived neurotrophic factor (BDNF) was associated with age-related changes in the amygdala volume, and Nemoto et al. [9] reported that the same BDNF allelic variant influenced age-related changes in brain morphology. The apolipoprotein E genotype has also been shown to have an impact on age-related GM volume loss [10]. The findings of these studies suggest that genetic variation may influence age-related changes in brain morphology. The anti-apoptotic protein B-cell CLL/lymphoma 2 (Bcl-2) is a major inhibitor of apoptotic and necrotic cell death [12]. Bcl-2 also plays critical roles in neuronal morphogenesis and synapticBcl-2 and Age-Related Gray Matter Volume Changesplasticity [13,14], and altered Bcl-2 function has been proposed to contribute to the impairment of cellular plasticity and resilience in neuropsychiatric patients [12]. Bcl-2 may support central neurons through intracellular calcium signaling, which stimulates the regenerative response and neuronal differentiation [15], and this mechanism may influence aging processes 15857111 and pathogenesis in neurodegenerative disease [16]. These findings collectively suggest that Bcl-2 may play a critical role in the modulation of aging processes in the brain [17,18]. Uemura et al. [19] recently demonstrated that the intronic single nucleotide polymorphism (SNP) Bcl-2 rs956572 influences Bcl-2 function in B lymphoblast cell lines derived from bipolar disorder patients. The levels of Bcl-2 mRNA and protein were lowest in cell lines of patients with the G/G genotype, compared to that of patients with the other functional genotypes, G/A and A/ A. In contrast, an earlier study using similar cell lines found that the A/A genotype was associated with significantly lower Bcl-2 expression and greater cellular sensitivity to stress-induced apoptosis, compared with the G/G genotype [20]. However, both studies showed that the Bcl-2 polymorphism was associated with intracellular calcium homeostasis in lymphoblast cells derived from bipolar disorder patients. A growing body of evidence indicates that a relationship exists between altered Bcl-2 expression and the neurodegenerative process [18], and that calcium signaling is responsible for neuronal aging and degeneration [21]. Increased vulnerability to Bcl-2related apoptosis.
