Dataset Information

Striatal proteomics offers clues on the inattention in early adult THRSP-overexpressing mice: Involvement of Snap25 gene

ABSTRACT: Attention-deficit/hyperactivity disorder, or ADHD, is a neurodevelopmental disorder characterized by inattention, hyperactivity, and impulsivity. Despite its high prevalence, the underlying molecular mechanisms of ADHD remain poorly understood. Recent studies have proposed that changes in the expression of genes involved in regulating synaptic transmission in the striatum may play a role in the pathogenesis of ADHD. To explore the molecular basis of ADHD, we conducted a study using proteomics to analyze whole striatal tissues from early adult thyroid hormone-responsive protein overexpressing (THRSP-OE) mice, which displayed defining characteristics of predominantly inattentive ADHD (ADHD-PI). We focused on the striatal brain region for its critical role in the regulation of attention, motivation, and reward processing. Moreover, the striatum modulates dopaminergic pathways that are known to be impaired in ADHD. Our analysis revealed an innate overexpression of Snap25 protein in THRSP-OE mice, which indicates possible altered SNARE protein complex and potential neurotransmitter dysregulation. Furthermore, a binding affinity study showed reduced dopamine D1 receptor binding concentrations in THRSP-OE mice and pronounced low dopamine levels using enzyme-linked immunosorbent assays measuring DA concentrations. Interestingly, repeated seven-day injections of Methylphenidate improved the low DA, reducing the theta/beta ratio in this animal model. These findings suggest new markers specific to the ADHD-PI presentation and further support the role of Snap25 dysregulation and possible SNARE protein complex alterations in ADHD-PI.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Eugene C Yi

LAB HEAD: Eugene C. Yi

PROVIDER: PXD051619 | Pride | 2025-09-22

REPOSITORIES: Pride

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			Action	DRS
	20201203_ADHD_STR_ThrspOE_FN01_01.raw	Raw
	20201203_ADHD_STR_ThrspOE_FN01_02.raw	Raw
	20201203_ADHD_STR_ThrspOE_FN02_01.raw	Raw
	20201203_ADHD_STR_ThrspOE_FN02_02.raw	Raw
	20201203_ADHD_STR_ThrspOE_FN03_01.raw	Raw

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Publications

Unraveling Predominantly Inattentive ADHD (ADHD-PI): Insights from Proteomic Analysis of the Striatum of Thyroid Hormone-Responsive Protein (THRSP)-Overexpressing Mice.

Custodio Raly James Perez RJP Sayson Leandro Val LV Cho Ara A Jung Hyeryeon H Ortiz Darlene Mae DM Lee Hyun Jun HJ Alyan Emad E Wascher Edmund E Getzmann Stephan S Kim Mikyung M Kim Kyeong-Man KM Yi Eugene C EC Kim Hee Jin HJ Cheong Jae Hoon JH

Molecular neurobiology 20250610 10

Attention-deficit/hyperactivity disorder, or ADHD, is a neurodevelopmental disorder with poorly understood molecular mechanisms. Recent studies have proposed that gene expression involved in regulating synaptic transmission in the striatum may play a role in ADHD pathogenesis. To explore the molecular basis of ADHD, we utilized proteomic analysis using whole striatal tissues from early adult thyroid hormone-responsive protein-overexpressing (THRSP-OE) mice, which displayed defining characteristi ...[more]

PMID: 40493342

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