Exercised blood plasma promotes hippocampal neurogenesis in the Alzheimer's disease rat brain

Cecilie Skarstad Norevik; Aleksi M Huuha; Ragnhild N Røsbjørgen; Linda Hildegard Bergersen; Kamilla Jacobsen; Rodrigo Miguel-Dos-Santos; Liv Ryan; Belma Skender; Jose Bianco N Moreira; Asgeir Kobro-Flatmoen; Menno P Witter; Nathan Scrimgeour; Atefe R Tari

doi:10.1016/j.jshs.2023.07.003

Exercised blood plasma promotes hippocampal neurogenesis in the Alzheimer's disease rat brain

J Sport Health Sci. 2024 Mar;13(2):245-255. doi: 10.1016/j.jshs.2023.07.003. Epub 2023 Jul 25.

Affiliations

¹ Cardiac Exercise Research Group (CERG), Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, 7491, Trondheim, Norway; Department of Neurology and Clinical Neurophysiology, St. Olavs University Hospital, 7030, Trondheim, Norway.
² Cardiac Exercise Research Group (CERG), Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, 7491, Trondheim, Norway.
³ Institute of Oral Biology, University of Oslo, 0372, Oslo, Norway.
⁴ Cardiac Exercise Research Group (CERG), Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, 7491, Trondheim, Norway; Department of Physiology, Federal University of Sergipe, São Cristóvão, 49100-000, Sergipe, Brazil.
⁵ Centre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, 7491, Trondheim, Norway.
⁶ Kavli Institute for Systems Neuroscience, Centre for Neural Computation, and Egil and Pauline Braathen and Fred Kavli Centre for Cortical Microcircuits, Norwegian University of Science and Technology, 7030, Trondheim, Norway.
⁷ Kavli Institute for Systems Neuroscience, Centre for Neural Computation, and Egil and Pauline Braathen and Fred Kavli Centre for Cortical Microcircuits, Norwegian University of Science and Technology, 7030, Trondheim, Norway; K.G. Jebsen Centre for Alzheimer's Disease, Norwegian University of Science and Technology, 7030, Trondheim, Norway.
⁸ Cardiac Exercise Research Group (CERG), Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, 7491, Trondheim, Norway; Department of Neurology and Clinical Neurophysiology, St. Olavs University Hospital, 7030, Trondheim, Norway. Electronic address: atefe.r.tari@ntnu.no.

Abstract

Background: Exercise training promotes brain plasticity and is associated with protection against cognitive impairment and Alzheimer's disease (AD). These beneficial effects may be partly mediated by blood-borne factors. Here we used an in vitro model of AD to investigate effects of blood plasma from exercise-trained donors on neuronal viability, and an in vivo rat model of AD to test whether such plasma impacts cognitive function, amyloid pathology, and neurogenesis.

Methods: Mouse hippocampal neuronal cells were exposed to AD-like stress using amyloid-β and treated with plasma collected from human male donors 3 h after a single bout of high-intensity exercise. For in vivo studies, blood was collected from exercise-trained young male Wistar rats (high-intensity intervals 5 days/week for 6 weeks). Transgenic AD rats (McGill-R-Thy1-APP) were injected 5 times/fortnight for 6 weeks at 2 months or 5 months of age with either (a) plasma from the exercise-trained rats, (b) plasma from sedentary rats, or (c) saline. Cognitive function, amyloid plaque pathology, and neurogenesis were assessed. The plasma used for the treatment was analyzed for 23 cytokines.

Results: Plasma from exercised donors enhanced cell viability by 44.1% (p = 0.032) and reduced atrophy by 50.0% (p < 0.001) in amyloid-β-treated cells. In vivo exercised plasma treatment did not alter cognitive function or amyloid plaque pathology but did increase hippocampal neurogenesis by ∼3 fold, regardless of pathological stage, when compared to saline-treated rats. Concentrations of 7 cytokines were significantly reduced in exercised plasma compared to sedentary plasma.

Conclusion: Our proof-of-concept study demonstrates that plasma from exercise-trained donors can protect neuronal cells in culture and promote adult hippocampal neurogenesis in the AD rat brain. This effect may be partly due to reduced pro-inflammatory signaling molecules in exercised plasma.

Keywords: Cytokines; High-intensity interval training; Inflammation; Neurons; Plasma transfusion.

MeSH terms

Alzheimer Disease*
Amyloid beta-Peptides / metabolism
Animals
Cytokines
Hippocampus / pathology
Humans
Male
Mice
Neurogenesis / physiology
Plaque, Amyloid / pathology
Plaque, Amyloid / prevention & control
Plasma / metabolism
Rats
Rats, Wistar

Substances

Amyloid beta-Peptides
Cytokines