Evaluating neuroinflammation in a mouse model of dopamine depletion. Sex differences and developmental impact.

Abstract

Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental syndrome influenced by both environmental and genetic factors, such as catecholamine dysfunctions, although neuroinflammation is suggested as a significant trigger. This study investigates the link between dopaminergic deficiency and neuroinflammation in ADHD using a 6-hydroxydopamine (6-OHDA) mouse model and abscisic acid (ABA) treatment, which has anti-inflammatory effects. In two-month-old mice, sex-dependent effects were observed: females exhibited increased pain sensitivity and inflammation, while males showed hyperactivity. ABA treatment reduced hypersensitivity and inflammation in females and alleviated hyperactivity in males. Both sexes displayed memory deficits unaffected by ABA. Prolonged ABA treatment led to partial recovery of behavioral symptoms in females at three months. The 6-OHDA lesion also altered microglial morphology and cytokine levels, which ABA restored. The findings highlight the importance of sex and age in the dopaminergic lesions' effects and suggest that ABA can help manage ADHD symptoms by restoring microglial function and enhancing GABAergic signaling.