Gene expression plays a fundamental role in the development and function of the nervous system. Interactions between the products of gene expression and the environment are crucial to the adaptive response of the nervous system. Variations in gene expression, even small ones, can significantly affect the activity of the system. Changes in regulatory genes during development can increase susceptibility to neurodevelopmental conditions such as autism, ADHD, and schizophrenia. Alterations in gene expression are also implicated in psychiatric disorders such as depression and OCD, and in the reinforcement aspects of addiction. Furthermore, persistent alterations in gene expression may be involved in the initiation and maintenance of pathological states such as seizures and neurodegenerative diseases such as Parkinson’s and Alzheimer’s. However, it is essential to recognize that associations between diseases and products of gene expression do not imply genetic determinism. Although many of these diseases have an inherited genetic basis, usually in the form of susceptibility genes, it is the ongoing interaction between the products of gene expression and the environment that shapes the activity of the nervous system. (Marcotte et al., 2003)
cDNA microarrays:
cDNA microarrays allow rapid and accurate quantification of a large number of potential changes in gene expression simultaneously. This technique, based on the hybridization of complementary DNA molecules, enables large-scale analysis of expressed genes. cDNA fragments are arranged in a high-density matrix, and hybridization with tissue samples allows the determination of the expression levels of thousands of genes simultaneously. This ability to examine the expression of numerous genes at the same time paves the way for the analysis of the expression state of an individual in a single experiment, especially with advances in genomic sequencing. (Marcotte et al., 2003)
Applications in Schizophrenia:
Schizophrenia is a complex disease with genetic, environmental, and developmental components, making it ideal for large-scale gene expression analysis with cDNA microarrays. Microarray studies of postmortem brain tissue from patients with schizophrenia have identified alterations in the expression of genes involved in presynaptic function, glutamatergic and GABAergic neurotransmission, and the regulation of G-protein signaling. Consistent results point to a reduction in RGS4 expression in the prefrontal cortex of patients with schizophrenia. Other studies have highlighted reduced expression of genes related to myelination, raising the possibility that oligodendrocytes are functionally deficient in schizophrenia. (Marcotte et al., 2003)
Applications in Alzheimer’s:
Alzheimer’s disease (AD) is the most prevalent form of age-related neurodegeneration. It is a progressive disease leading to cognitive impairment and is characterized by neuropathological changes such as extracellular amyloid plaques, intracellular neurofibrillary tangles of abnormally phosphorylated tau protein, and degeneration of basal forebrain cholinergic neurons. Microarray studies in AD have revealed significant alterations in gene expression in several brain regions, including the hippocampus, cingulate cortex, and amygdala. (Marcotte et al., 2003)
Proteomic Approaches:
Proteomics, which focuses on large-scale analysis of proteins, complements genomics and cDNA microarrays. Proteins, the end products of gene expression, are regulated by other cellular constituents and undergo post-translational modifications that influence their functions. Proteomics seeks to elucidate the role of protein expression, including protein-protein interactions and the formation of protein complexes. Advances in mass spectrometry and protein isolation techniques have advanced proteomic approaches, allowing the identification and analysis of proteins in complex mixtures. (Marcotte et al., 2003)
Proteomics in Alzheimer’s:
AD, with its extracellular amyloid plaques and intracellular neurofibrillary tangles, is a disease in which protein-protein interactions likely play a crucial role. Proteomic analysis in AD can confirm and complement genomic studies by revealing alterations in protein expression and post-translational modifications. Proteomic studies have identified proteins differentially expressed in several brain regions in AD, including proteins related to the inflammatory response, energy metabolism, synaptic function, and oxidative stress. (Marcotte et al., 2003)
Conclusions:
Advances in genomics and proteomics, including cDNA microarrays and mass spectrometry, have revolutionized biomedical research, especially in neuroscience. The ability to analyze the expression of thousands of genes and proteins simultaneously, combined with bioinformatics, is providing a more complete view of complex biological processes and diseases. In neuroscience, the application of genomics and proteomics is particularly promising, considering the complexity and diversity of cellular interactions in the nervous system. Continued use of these techniques in post-mortem human tissues, animal models, and cell culture systems will allow a better understanding of the physiology of the nervous system under normal and pathological conditions, facilitating the discovery of potential drug targets for brain diseases. However, it is essential to remember that the interpretation of genomic and proteomic data requires careful analysis and a deep understanding of the biological processes involved. (Marcotte et al., 2003)
Reference:
MARCOTE, ER; SRIVASTAVA, LK; QUIRION, R. cDNA microarray and proteomic approaches in the study of brain diseases: focus on schizophrenia and Alzheimer’s disease. Pharmacology & Therapeutics, vol. 100, no. 1, p. 63–74, 2003.
