# Altered Co-Expression Patterns of Mitochondrial NADH-Dehydrogenase Genes in the Prefrontal Cortex of Rodent ADHD Models

## TL;DR

This study finds that mitochondrial genes in the prefrontal cortex show altered co-expression in rodent models of ADHD, suggesting mitochondria may play a role in the disorder.

## Contribution

The study identifies specific co-expression patterns of mitochondrial complex I genes in ADHD models, linking them to neural processes.

## Key findings

- ND1–ND6 genes show significantly enhanced co-expression in ADHD rodent models compared to controls.
- ND3 and ND4L expression is associated with neural tissue-specific genes only in ADHD models.
- DAT-Het rats show upregulated ND4L expression despite not exhibiting hyperactivity.

## Abstract

Altered mitochondrial function is implicated in disorders characterized by prefrontal cortex activation deficits, including attention deficit hyperactivity disorder (ADHD). The expression of mitochondrial DNA-coded respiratory chain complex I genes (ND1–ND6) in the prefrontal cortex of ADHD animal models was estimated in the present study. ND gene expression was assessed in two publicly available datasets: GSE117357 (Adgrl3 knockout mice) and GSE173926 (MYT1L heterozygous knockout mice). Additionally, we measured NDs gene expression via qPCR in dopamine transporter knockout (DAT-KO) rats and their heterozygous (DAT-Het) littermates. Transcriptomic analysis revealed consistent ND1–ND6 expression profiles across both datasets, and co-expression among ND genes was significantly enhanced in ADHD models compared to wild-type controls. Whole-transcriptome analysis identified associations between ND3 and ND4L expression and genes involved in neural tissue-specific processes, exclusively in ADHD models. In DAT-KO and DAT-Het rats, NDs gene co-expression increased. Furthermore, in DAT-Het rats, which do not exhibit hyperactivity, the upregulation of ND4L expression relative to wild-type littermates was demonstrated. The observed changes in mitochondrial complex I gene co-expression in ADHD models suggest mitochondria may serve as a prospective target for adjuvant therapy. These findings highlight the need for further investigation into mitochondrial contributions to ADHD pathophysiology.