# Mitochondrial Integrity and Kynurenine Pathway Enzyme Dynamics in the Hippocampus of Rats with Scopolamine-Induced Cognitive Deficits

## TL;DR

Short-term scopolamine exposure in rats does not disrupt hippocampal mitochondrial DNA or activate the kynurenine pathway, suggesting these changes are not involved in acute cognitive deficits.

## Contribution

The study demonstrates that short-term scopolamine exposure does not alter mitochondrial DNA or kynurenine pathway enzyme expression in the hippocampus.

## Key findings

- No significant mtDNA mutations or heteroplasmy changes were observed in the hippocampus of scopolamine-treated rats.
- Expression levels of kynurenine pathway enzymes and receptors remained unchanged in treated rats.
- Results suggest that acute pharmacological stress does not trigger mitochondrial or kynurenine pathway disruptions in the hippocampus.

## Abstract

Cognitive impairments, particularly in the context of neurodegenerative diseases, are associated with disruptions in mitochondrial function and key metabolic pathways. This study investigates the impact of short-term scopolamine exposure on mitochondrial DNA (mtDNA) stability and the kynurenine pathway (KP) in the hippocampus, a brain region central to learning and memory. We analyzed the mitochondrial D-loop region for mutations and heteroplasmy levels in hippocampal tissue from rats exposed to scopolamine (1 mg/kg/0.4 mL/cc i.p. x 14 days). Additionally, the expression of the KP enzymes kynurenine aminotransferase (KAT I, KAT II) and kynurenine 3-monooxygenase (KMO) and receptors aryl hydrocarbon receptor (Ahr) and G protein-coupled receptor 35 (GPR35) was evaluated using quantitative PCR. Neither significant mutation nor heteroplasmy changes were observed in the mtDNA D-loop region between the scopolamine-treated and control groups. Similarly, the hippocampal expression levels of the kat I, kat II, kmo and ahr and gpr35 genes remained unchanged, indicating no activation of this metabolic pathway under short-term scopolamine exposure. These findings suggest that the mitochondrial genome in the hippocampus remains stable under acute pharmacological stress induced by scopolamine, with no significant activation of the KP. These results underline the distinction between transient, reversible cognitive deficits and chronic neurodegenerative processes, providing insights for therapeutic approaches targeting specific stages of cognitive change.