Effect of Post‑Induction Treadmill Exercise on Hippocampal Agrin and Laminin in a Rat Model of Alzheimer’s Disease: Relevance to Hippocampal Sclerosis

Background: Alzheimer’s disease (AD) is the most common cause of dementia. Exercise is a practical and cost‑effective intervention with neuroprotective effects. We examined whether four weeks of moderate treadmill exercise alter hippocampal levels of two extracellular‑matrix (ECM) proteins—agrin and laminin—implicated in synaptic stability and blood–brain barrier function and considered the relevance to hippocampal sclerosis (HS) as a co‑pathology in late‑life dementia. Methods: Male Wistar rats (n=24; 8 weeks) were assigned to Aβ1–42‑injected (Aβ), Aβ + exercise (Aβ+Ex), or control groups (n=8/group). After 7 days to allow early AD‑like pathology, the Aβ+Ex group completed 4 weeks of treadmill running (5 days/week; weeks 1–2: 2×15 min at 10 m/min; weeks 3–4: 2×15 min at 15 m/min). Spatial learning and memory were assessed using the Morris water maze (MWM) and probe trial. Hippocampal agrin and laminin levels were quantified post‑training. Results: Compared with Aβ rats, Aβ+Ex showed higher hippocampal agrin and laminin levels (p ≤ 0.001), and both Aβ and Aβ+Ex differed from controls (agrin: p ≤ 0.006 and p ≤ 0.003, respectively). Exercise partially normalized ECM protein levels and improved MWM performance. Conclusion: Post‑induction treadmill exercise modulates hippocampal agrin and laminin in an AD rat model, supporting ECM‑mediated mechanisms of cognitive benefit. Given prior links among ECM remodeling, neuronal loss/gliosis, and HS in aging and epilepsy, these findings may have relevance to hippocampal sclerosis, although HS pathology was not directly assessed here.