6th Edition of Neurology World Conference 2026

Abstract

Background: SRPK1 is a splicing-related protein that plays an important role in the development and function of the human brain. Alternative splicing enables significant molecular variety in the human nervous system, allowing hundreds of unique proteins to be produced from far fewer genes. This article presents evidence that SRPK1 has distinct spatiotemporal expression patterns enriched in processes related to neurodevelopmental disorders across development.

Material and method: We used the BrainSpan growing mammalian brain transcriptome to evaluate the distribution of SRPK1 throughout the entire brain. RNA sequencing data were gathered from 524 tissue samples recovered from 41 postmortem brains of physiologically normal individuals spanning early developing fetus(8 postconception weeks, PCW) to later life (40 years of age). The BrainSpan website (http://www.brainspan.org/rnaseq/search/index.html) provides information about tissue collection anddata processing. The RNA-seq datawere annotated with gene and exon information from GENCODE version 10 (GRCh37–Ensembl 65). Exon expression levels were quantified in RPKM (reads per kilobase permillion mapped reads) units. To better understand the function of SRPK1, we consulted the AllenHuman Brain Atlas (AHBA) dataset (https://human.brain-map.org),which includes information on the spatial gene expression of fifteen adult human brains.  We assessed the spatial correlation (using Pearson’s correlation coefficient) among all genes in the AHBA (19,991 genes) to determine the functional link between the SRPK1 gene and all other genes in the adolescent human brain by integrating all data from six donors (3902 samples). We assessed the spatiotemporal correlation (Pearson’s)among all exons (241,690 exons) in the BrainSpan dataset to determine their functional relationships with SRPK1 during development. Based on the relationships, genes were ranked in descending order. To develop a ranked gene list, the rank of each gene’s most highly correlated exon was assigned to each gene (https://genefriends.org). A functional annotation analysis was conducted on the top 1%of gene sets (strongest positive correlations). Using ToppGene, a functional annotation analysis was performed (https://toppgene.cchmc.org/).

Results: We found evidence that analyzing the spatiotemporal gene expression profile and identifying co-expressed genes reveals that SRPK1 expression is involved in various neurodevelopmental and somatic events throughout the lifetime. Our analysis showed that SRPK1 expression increases throughout the human brain immediately before birth, with significantly higher levels during the early PCW than during childhood and adulthood (p value < .0001) and marginally higher levels during childhood than during adulthood. The AHBA provides microarray gene expression profiles from hundreds of samples obtained from six adult human brains, providing a comprehensive examination of the local expression of genes in the human brain. Further, we mapped the top 3020 SRPK1-linked genes to a co-expression network to evaluate the strength of the connections between the basis of both spatial and temporal co-expression trends with SRPK1in the developing brain, and we may identify people. The phenotype associations early neurodevelopmental disorders of gait abnormalities.

Conclusion: Our findings highlight the importance of detailed maps of gene expression in the human brain for improved human-to-human translation and illustrate differences in SRPK1 expression across anatomical areas and developmental stages in healthy human brain tissue.