Deregulated mRNA and microRNA Expression Patterns in the Prefrontal Cortex of the BTBR Mouse Model of Autism.

ingentiumby ingentium

In Autism Literature.

Publication date: Apr 14, 2025

Autism spectrum disorder (ASD) is a neurodevelopmental condition caused by both genetic and environmental factors. Since no single gene variant accounts for more than 1% of the cases, the converging actions of ASD-related genes and other factors, including microRNAs (miRNAs), may contribute to ASD pathogenesis. To date, few studies have simultaneously investigated the mRNA and miRNA profiles in an ASD-relevant model. The BTBR mouse strain displays a range of behaviors with ASD-like features but little is known about the protein-coding and noncoding gene expression landscape that may underlie the ASD-like phenotype. Here we performed parallel mRNA and miRNA profiling using the prefrontal cortex (PFC) of BTBR and C57BL/6 J (B6) mice. This identified 1063 differentially expressed genes and 48 differentially expressed miRNAs. Integration of mRNA and miRNA data identified a strong inverse relationship between upregulated (DEGs) and downregulated miRNAs, and vice versa. Pathway analysis, taking account of the inverse relationship between differentially expressed miRNAs and their target mRNAs highlighted significant shared enrichment in immune signaling, myelination, and neurodevelopmental processes. Notably, miRNA changes were predicted to affect synapse-related functions but we did not find enrichment of protein-coding genes linked to cellular components or biological processes related to synapses in the PFC of BTBR mice, indicating processes may evade miRNA control. In contrast, other miRNAs were predicted to have extensive relationships with DEGs suggesting their role as potential hub coordinators of gene expression. Profiling findings were confirmed via qRT-PCR for representative protein-coding transcripts and miRNAs. Our study underscores the complex interplay between gene expression and miRNA regulation within immune and inflammatory pathways in the BTBR model, offering insights into the neurodevelopmental mechanisms of ASD. These results support the value of the BTBR mouse model and identify strategies that could adjust molecular pathways for therapeutic applications in ASD research.

Open Access PDF

Concepts Keywords
Autism Autism spectrum disorder
Btbr Inflammatory pathways
Environmental MiRNA
Mice MRNA
Pcr Prefrontal cortex

Semantics

Type Source Name
disease MESH Autism
disease MESH Autism spectrum disorder
disease MESH pathogenesis
drug DRUGBANK Huperzine B
disease MESH repression
disease MESH neurodevelopmental disorders
drug DRUGBANK Trestolone
drug DRUGBANK Esomeprazole
disease MESH anomalies
drug DRUGBANK Indoleacetic acid
drug DRUGBANK Water
drug DRUGBANK Isoxaflutole
disease MESH bipolar disorder
drug DRUGBANK D-Alanine
drug DRUGBANK Riboprine
drug DRUGBANK Ranitidine
pathway REACTOME Extracellular matrix organization
pathway KEGG Adherens junction
drug DRUGBANK Calcium
pathway REACTOME Apoptosis
pathway REACTOME Metabolism
pathway REACTOME GPCR ligand binding
disease MESH schizophrenia
disease MESH intellectual disability
disease MESH oxidative stress
disease MESH syndrome
drug DRUGBANK L-Valine
pathway KEGG Chemokine signaling pathway
pathway REACTOME Axon guidance
pathway KEGG Focal adhesion
drug DRUGBANK Coenzyme M
disease MESH tic
drug DRUGBANK Ethionamide
pathway KEGG Ras signaling pathway
pathway REACTOME Autophagy
drug DRUGBANK Flunarizine
disease MESH inflammation
drug DRUGBANK Myricetin
drug DRUGBANK Trihexyphenidyl
drug DRUGBANK Profenamine
drug DRUGBANK Zinc
disease MESH neuroinflammation
pathway KEGG Calcium signaling pathway
pathway REACTOME Signal Transduction
pathway KEGG Metabolic pathways
disease MESH morbidities
disease MESH mental disorders
pathway REACTOME Immune System
disease MESH haploinsufficiency
disease MESH epilepsy
disease MESH multiple sclerosis
disease MESH cognitive impairments
disease MESH depression
disease MESH brain disorders
drug DRUGBANK Etoperidone
pathway REACTOME Reproduction
disease MESH comorbidity
drug DRUGBANK Minaprine
drug DRUGBANK Diethylstilbestrol
drug DRUGBANK Metamfetamine
pathway REACTOME Methylation
disease MESH temporal lobe epilepsy
disease MESH status epilepticus
disease MESH Alzheimer’s diseases
disease MESH multiple myeloma
disease MESH Leukemia
drug DRUGBANK L-Leucine
drug DRUGBANK Aminosalicylic Acid
disease MESH Death
disease MESH stroke
drug DRUGBANK Carboxyamidotriazole
drug DRUGBANK Valproic Acid
disease MESH Pitt Hopkins syndrome
disease MESH neurodegenerative disease
pathway REACTOME Neurodegenerative Diseases
drug DRUGBANK Lauric Acid
disease MESH microcephaly
disease MESH seizures
disease MESH Thrush
disease MESH autoimmunity
disease MESH major depressive disorder
disease MESH memory deficits
disease MESH mitochondrial dysfunction

Original Article

(Visited 1 times, 1 visits today)

Leave a Comment

Your email address will not be published. Required fields are marked *

Deregulated mRNA and microRNA Expression Patterns in the Prefrontal Cortex of the BTBR Mouse Model of Autism.

ingentiumby ingentium

In Autism Literature.

Publication date: Apr 14, 2025

Autism spectrum disorder (ASD) is a neurodevelopmental condition caused by both genetic and environmental factors. Since no single gene variant accounts for more than 1% of the cases, the converging actions of ASD-related genes and other factors, including microRNAs (miRNAs), may contribute to ASD pathogenesis. To date, few studies have simultaneously investigated the mRNA and miRNA profiles in an ASD-relevant model. The BTBR mouse strain displays a range of behaviors with ASD-like features but little is known about the protein-coding and noncoding gene expression landscape that may underlie the ASD-like phenotype. Here we performed parallel mRNA and miRNA profiling using the prefrontal cortex (PFC) of BTBR and C57BL/6 J (B6) mice. This identified 1063 differentially expressed genes and 48 differentially expressed miRNAs. Integration of mRNA and miRNA data identified a strong inverse relationship between upregulated (DEGs) and downregulated miRNAs, and vice versa. Pathway analysis, taking account of the inverse relationship between differentially expressed miRNAs and their target mRNAs highlighted significant shared enrichment in immune signaling, myelination, and neurodevelopmental processes. Notably, miRNA changes were predicted to affect synapse-related functions but we did not find enrichment of protein-coding genes linked to cellular components or biological processes related to synapses in the PFC of BTBR mice, indicating processes may evade miRNA control. In contrast, other miRNAs were predicted to have extensive relationships with DEGs suggesting their role as potential hub coordinators of gene expression. Profiling findings were confirmed via qRT-PCR for representative protein-coding transcripts and miRNAs. Our study underscores the complex interplay between gene expression and miRNA regulation within immune and inflammatory pathways in the BTBR model, offering insights into the neurodevelopmental mechanisms of ASD. These results support the value of the BTBR mouse model and identify strategies that could adjust molecular pathways for therapeutic applications in ASD research.

Open Access PDF

Concepts Keywords
Autism Autism spectrum disorder
Btbr Inflammatory pathways
Environmental MiRNA
Mice MRNA
Pcr Prefrontal cortex

Semantics

Type Source Name
disease MESH Autism
disease MESH Autism spectrum disorder
disease MESH pathogenesis
drug DRUGBANK Huperzine B
disease MESH repression
disease MESH neurodevelopmental disorders
drug DRUGBANK Trestolone
drug DRUGBANK Esomeprazole
disease MESH anomalies
drug DRUGBANK Indoleacetic acid
drug DRUGBANK Water
drug DRUGBANK Isoxaflutole
disease MESH bipolar disorder
drug DRUGBANK D-Alanine
drug DRUGBANK Riboprine
drug DRUGBANK Ranitidine
pathway REACTOME Extracellular matrix organization
pathway KEGG Adherens junction
drug DRUGBANK Calcium
pathway REACTOME Apoptosis
pathway REACTOME Metabolism
pathway REACTOME GPCR ligand binding
disease MESH schizophrenia
disease MESH intellectual disability
disease MESH oxidative stress
disease MESH syndrome
drug DRUGBANK L-Valine
pathway KEGG Chemokine signaling pathway
pathway REACTOME Axon guidance
pathway KEGG Focal adhesion
drug DRUGBANK Coenzyme M
disease MESH tic
drug DRUGBANK Ethionamide
pathway KEGG Ras signaling pathway
pathway REACTOME Autophagy
drug DRUGBANK Flunarizine
disease MESH inflammation
drug DRUGBANK Myricetin
drug DRUGBANK Trihexyphenidyl
drug DRUGBANK Profenamine
drug DRUGBANK Zinc
disease MESH neuroinflammation
pathway KEGG Calcium signaling pathway
pathway REACTOME Signal Transduction
pathway KEGG Metabolic pathways
disease MESH morbidities
disease MESH mental disorders
pathway REACTOME Immune System
disease MESH haploinsufficiency
disease MESH epilepsy
disease MESH multiple sclerosis
disease MESH cognitive impairments
disease MESH depression
disease MESH brain disorders
drug DRUGBANK Etoperidone
pathway REACTOME Reproduction
disease MESH comorbidity
drug DRUGBANK Minaprine
drug DRUGBANK Diethylstilbestrol
drug DRUGBANK Metamfetamine
pathway REACTOME Methylation
disease MESH temporal lobe epilepsy
disease MESH status epilepticus
disease MESH Alzheimer’s diseases
disease MESH multiple myeloma
disease MESH Leukemia
drug DRUGBANK L-Leucine
drug DRUGBANK Aminosalicylic Acid
disease MESH Death
disease MESH stroke
drug DRUGBANK Carboxyamidotriazole
drug DRUGBANK Valproic Acid
disease MESH Pitt Hopkins syndrome
disease MESH neurodegenerative disease
pathway REACTOME Neurodegenerative Diseases
drug DRUGBANK Lauric Acid
disease MESH microcephaly
disease MESH seizures
disease MESH Thrush
disease MESH autoimmunity
disease MESH major depressive disorder
disease MESH memory deficits
disease MESH mitochondrial dysfunction

Original Article

Leave a Comment

Your email address will not be published. Required fields are marked *

Deregulated mRNA and microRNA Expression Patterns in the Prefrontal Cortex of the BTBR Mouse Model of Autism.

ingentiumby ingentium

In Autism Literature.

Publication date: Apr 14, 2025

Autism spectrum disorder (ASD) is a neurodevelopmental condition caused by both genetic and environmental factors. Since no single gene variant accounts for more than 1% of the cases, the converging actions of ASD-related genes and other factors, including microRNAs (miRNAs), may contribute to ASD pathogenesis. To date, few studies have simultaneously investigated the mRNA and miRNA profiles in an ASD-relevant model. The BTBR mouse strain displays a range of behaviors with ASD-like features but little is known about the protein-coding and noncoding gene expression landscape that may underlie the ASD-like phenotype. Here we performed parallel mRNA and miRNA profiling using the prefrontal cortex (PFC) of BTBR and C57BL/6 J (B6) mice. This identified 1063 differentially expressed genes and 48 differentially expressed miRNAs. Integration of mRNA and miRNA data identified a strong inverse relationship between upregulated (DEGs) and downregulated miRNAs, and vice versa. Pathway analysis, taking account of the inverse relationship between differentially expressed miRNAs and their target mRNAs highlighted significant shared enrichment in immune signaling, myelination, and neurodevelopmental processes. Notably, miRNA changes were predicted to affect synapse-related functions but we did not find enrichment of protein-coding genes linked to cellular components or biological processes related to synapses in the PFC of BTBR mice, indicating processes may evade miRNA control. In contrast, other miRNAs were predicted to have extensive relationships with DEGs suggesting their role as potential hub coordinators of gene expression. Profiling findings were confirmed via qRT-PCR for representative protein-coding transcripts and miRNAs. Our study underscores the complex interplay between gene expression and miRNA regulation within immune and inflammatory pathways in the BTBR model, offering insights into the neurodevelopmental mechanisms of ASD. These results support the value of the BTBR mouse model and identify strategies that could adjust molecular pathways for therapeutic applications in ASD research.

Open Access PDF

Concepts Keywords
Autism Autism spectrum disorder
Btbr Inflammatory pathways
Environmental MiRNA
Mice MRNA
Pcr Prefrontal cortex

Semantics

Type Source Name
disease MESH Autism
disease MESH Autism spectrum disorder
disease MESH pathogenesis
drug DRUGBANK Huperzine B
disease MESH repression
disease MESH neurodevelopmental disorders
drug DRUGBANK Trestolone
drug DRUGBANK Esomeprazole
disease MESH anomalies
drug DRUGBANK Indoleacetic acid
drug DRUGBANK Water
drug DRUGBANK Isoxaflutole
disease MESH bipolar disorder
drug DRUGBANK D-Alanine
drug DRUGBANK Riboprine
drug DRUGBANK Ranitidine
pathway REACTOME Extracellular matrix organization
pathway KEGG Adherens junction
drug DRUGBANK Calcium
pathway REACTOME Apoptosis
pathway REACTOME Metabolism
pathway REACTOME GPCR ligand binding
disease MESH schizophrenia
disease MESH intellectual disability
disease MESH oxidative stress
disease MESH syndrome
drug DRUGBANK L-Valine
pathway KEGG Chemokine signaling pathway
pathway REACTOME Axon guidance
pathway KEGG Focal adhesion
drug DRUGBANK Coenzyme M
disease MESH tic
drug DRUGBANK Ethionamide
pathway KEGG Ras signaling pathway
pathway REACTOME Autophagy
drug DRUGBANK Flunarizine
disease MESH inflammation
drug DRUGBANK Myricetin
drug DRUGBANK Trihexyphenidyl
drug DRUGBANK Profenamine
drug DRUGBANK Zinc
disease MESH neuroinflammation
pathway KEGG Calcium signaling pathway
pathway REACTOME Signal Transduction
pathway KEGG Metabolic pathways
disease MESH morbidities
disease MESH mental disorders
pathway REACTOME Immune System
disease MESH haploinsufficiency
disease MESH epilepsy
disease MESH multiple sclerosis
disease MESH cognitive impairments
disease MESH depression
disease MESH brain disorders
drug DRUGBANK Etoperidone
pathway REACTOME Reproduction
disease MESH comorbidity
drug DRUGBANK Minaprine
drug DRUGBANK Diethylstilbestrol
drug DRUGBANK Metamfetamine
pathway REACTOME Methylation
disease MESH temporal lobe epilepsy
disease MESH status epilepticus
disease MESH Alzheimer’s diseases
disease MESH multiple myeloma
disease MESH Leukemia
drug DRUGBANK L-Leucine
drug DRUGBANK Aminosalicylic Acid
disease MESH Death
disease MESH stroke
drug DRUGBANK Carboxyamidotriazole
drug DRUGBANK Valproic Acid
disease MESH Pitt Hopkins syndrome
disease MESH neurodegenerative disease
pathway REACTOME Neurodegenerative Diseases
drug DRUGBANK Lauric Acid
disease MESH microcephaly
disease MESH seizures
disease MESH Thrush
disease MESH autoimmunity
disease MESH major depressive disorder
disease MESH memory deficits
disease MESH mitochondrial dysfunction

Original Article

Leave a Comment

Your email address will not be published. Required fields are marked *