Bipolar disorder (BPD) is a serious psychiatric condition that is characterized by the frequent shifting of mood patterns, ranging from manic to depressive episodes. Although there are already treatment strategies that aim at regulating the manifestations of this disorder, its etiology remains unclear and continues to be a question of interest within the scientific community. The development of RNA sequencing techniques has provided newer and better approaches to studying disorders at the transcriptomic level. Hence, using RNA-seq data, we employed intramodular connectivity analysis and network pharmacology assessment of disease-associated variants to elucidate the biological pathways underlying the complex nature of BPD. This study was intended to characterize the expression profiles obtained from three regions in the brain, which are the nucleus accumbens (nAcc), the anterior cingulate cortex (AnCg), and the dorsolateral prefrontal cortex (DLPFC), provide insights into the specific roles of these regions in the onset of the disorder, and present potential targets for drug design and development. The nAcc was found to be highly associated with genes responsible for the deregulated transcription of neurotransmitters, while the DLPFC was greatly correlated with genes involved in the impairment of components crucial in neurotransmission. The AnCg did show association with some of the expressions, but the relationship was not as strong as the other two regions. Furthermore, disease-associated variants or single nucleotide polymorphisms (SNPs) were identified among the significant genes in BPD, which suggests the genetic interrelatedness of such a disorder and other mental illnesses. , , and were the genes with disease-associated variants expressed in the nAcc; and were the genes with disease-associated variants expressed in the AnCg; and , , , , and were the genes with disease-associated variants expressed in the DLPFC. Aside from unraveling the molecular and cellular mechanisms behind the expression of BPD, this investigation was envisioned to propose a new research pipeline in studying the transcriptome of psychiatric disorders to support and improve existing studies.
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http://dx.doi.org/10.3390/biology13100787 | DOI Listing |
Alzheimers Dement
December 2024
UK Dementia Research Institute, London, United Kingdom.
Background: Microglia are key players in Alzheimer's disease (AD): Genetic risk for AD is enriched in microglial enhancers, and microglial gene regulatory networks have been shown to be disrupted in AD. Here, we studied polygenic and variant-specific (APOE) risk burden for AD in a xenotransplantation model of AD and human post-mortem brain tissue.
Method: We profiled gene regulation by RNA-seq and ATAC-seq in human iPS-derived microglia, xenotransplanted into the APPNL-G-F mouse model of AD.
Alzheimers Dement
December 2024
University of Connecticut, Storrs, CT, USA.
Background: With insight into the elevated levels of phosphorylation of diseased tau, it is believed that specific modifications occur in a time-dependent manner that contribute to tau's role in Alzheimer's disease pathogenesis and progression. Present methods to obtain phospho-tau (p-tau) from post-mortem tissue or recombinantly are insufficient to answer the foremost questions in the field, and there is currently no way to study each disease-relevant modification reproducibly or in isolation. To this point, learning about tau phosphorylation at the resolution of a single modification has been a major obstacle in clarifying whether certain sites are causative of disease or just a by-product of other harmful mechanisms.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of California, Irvine, Irvine, CA, USA.
Background: Alzheimer's disease (AD), characterized by tau lesions and amyloid plaques, has traditionally been investigated within the cortical domain. Recent neuroimaging studies have implicated micro- and macrostructural abnormalities in cortical layers during the progression of AD. While examinations from diverse brain regions have contributed to comprehending the regional severity, these approaches have constrained the ability to delineate cortical alterations in AD.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Boston Children's Hospital, Boston, MA, USA.
Background: Alzheimer's disease (AD), an age-associated neurodegenerative disorder, is characterized by progressive neuronal loss and the accumulation of misfolded proteins such as amyloid-β and tau. While neuroinflammation, mediated by microglia and brain-resident macrophages, plays a pivotal role in AD pathogenesis, the intricate interactions among age, genes, and other risk factors remain elusive. Somatic mutations, known to accumulate with age, instigate clonal expansion across diverse cell types, impacting both cancer and non-cancerous conditions.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of California, Irvine, Irvine, CA, USA.
Background: A case study on a PSEN1 (E280A) carrier with APOECh (R136S) mutation revealed changes in APOE protein function led to a protective effect on AD outcomes. Notably, there is an intriguing disparity between the two hallmark pathologies: a reduction in tauopathy but no change in plaque burden. Given that the APOE protein is predominantly produced by astrocytes and activated microglia, and the APOE gene is among the disease-associated microglia (DAM) genes, it is conceivable that the variance in pathological outcomes may be rooted in the glial response.
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