Hippocampal neurogenesis is improved by exercise in heart failure in rats

Background: Heart failure (HF) is commonly associated with brain atrophy, including in the hippocampus. This may be a consequence of reduced neurogenesis in the dentate gyrus. Exercise training (EX) may improve neurogenesis in the setting of HF. Using a rodent model of HF, this study tested the hypothesis that EX recovers reduced neurogenesis in the dentate gyrus in the setting of HF. Methods: Male Sprague Dawley rats underwent either a sham (Sham; n =6-7) or left anterior descending coronary artery ligation (model of HF; n=12-13 ). HF rats were subdivided into sedentary (HF-SED; n =5-6) or EX (HF-EX ; n =7). Exercise consisted of progressive treadmill running (3-days/week). Injections of 5-bromo-2'-deoxyuridine (BrdU; 50μg/kg/day for three days) were performed 1-week post ligation (prior to the initiation of exercise training) and injections of 5-ethynyl-2’-deoxyuridine (EdU; 50ug/kg/day for 3-days) were performed ten-weeks post-ligation (at the end of the exercise training protocol). BrdU and EdU are thymine analogues used to assess cell proliferation. Animals were euthanized at 12-weeks post ligation, and their brains were harvested and stained for BrdU, EdU, and counterstained for neuronal N (NeuN) to quantify neurogenesis. Results: The number of BrdU + cells (HF-SED: 53±34, Sham-SED:36±27 cells/mm 2 ) and EdU + cells (HF-SED: 31±13, Sham-SED:33±11 cells/mm 2 ) as well as BrdU + cells (HF-SED: 52±33, Sham-SED:35±26 cells/mm 2 ) and EdU + cells (HF-SED: 24±16, Sham-SED:27±9 cells/mm 2 ) co-labeled with NeuN + in the dentate gyrus were similar between HF-SED and sham-SED groups (P≥0.54). This suggests that indicators of baseline and terminal neurogenesis were not affected by HF. BrdU + staining (HF-EX:22±25 cells/mm 2 ) or NeuN co-labelling (HF-EX:22±25 cells/mm 2 ) was not affected by exercise training (P≥0.14). However, the number of EdU + cells was greater in the HF-EX group (HF-EX:62±28) compared to the Sham-SED group (P=0.04) and HF-SED group (P=0.03). Additionally, the number of EdU + (HF-EX: 42±14) cells co-labeled with NeuN + was greater in the HF-EX vs. Sham-SED group (P=0.05) and increases in the HF-EX vs. HF-SED groups approached significance (P=0.07). This suggests that indicators of terminal neurogenesis were augmented by exercise training in the setting of HF. Conclusions: HF did not negatively affect neurogenesis in the dentate gyrus, but exercise training increased it. Based on the present data, it is uncertain if exercise training can ameliorate HF-induced neurological deficits. Nonetheless, the brains of rats with HF were responsive to exercise training, suggesting it can be used to improve brain health in this clinical population. Heart & Stroke Foundation, NSERC This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

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