Age-related changes in the architecture and biochemical markers levels in motor-related cortical areas of SHR rats-an ADHD animal model

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder whose exact pathophysiology has not been fully understood yet. Numerous studies have suggested disruptions in the cellular architecture and neuronal activity within brain structures of individuals with ADHD, accompanied by imbalances in the immune system, oxidative stress, and metabolism. This study aims to assess two functionally and histologically distinct brain areas involved in motor control and coordination: the motor cortex (MC) and prefrontal cortex (PFC). Namely, the morphometric analysis of the MC throughout the developmental stages of Spontaneously Hypertensive Rats (SHRs) and Wistar Kyoto Rats (WKYs). Additionally, the study aimed to investigate the levels and activities of specific immune, oxidative stress, and metabolic markers in the PFC of juvenile and maturing SHRs in comparison to WKYs. The most significant MC volume reductions occurred in juvenile SHRs, accompanied by alterations in neuronal density in these brain areas compared to WKYs. Furthermore, juvenile SHRs exhibit heightened levels and activity of various markers, including interleukin-1α (IL-1α), IL-6, serine/threonine-protein mammalian target of rapamycin, RAC-alpha serine/threonine-protein kinase, glucocorticoid receptor β, malondialdehyde, sulfhydryl groups, superoxide dismutase, peroxidase, glutathione reductase, glutathione S-transferase, glucose, fructosamine, iron, lactic acid, alanine, aspartate transaminase, and lactate dehydrogenase. Significant changes in the MC morphometry and elevated levels of inflammatory, oxidative, and metabolic markers in PFC might be associated with disrupted brain development and maturation in ADHD.