PMID- 29477301 OWN - NLM STAT- MEDLINE DCOM- 20181105 LR - 20211204 IS - 1873-7064 (Electronic) IS - 0028-3908 (Linking) VI - 133 DP - 2018 May 1 TI - Physical exercise prevents cognitive impairment by enhancing hippocampal neuroplasticity and mitochondrial function in doxorubicin-induced chemobrain. PG - 451-461 LID - S0028-3908(18)30070-4 [pii] LID - 10.1016/j.neuropharm.2018.02.013 [doi] AB - Although chemotherapy increases the survival rate of patients with various cancers, such treatment can induce acute or long-term cognitive dysfunction a phenomenon known as post-chemotherapy cognitive impairment (PCCI) or "chemobrain." Exercise is known to positively affect brain function. Thus, the present study aimed to determine whether symptoms of chemobrain and disruptions in the neuroplasticity and functioning of hippocampal mitochondria can be prevented or relieved by exercise. Wistar rats were separated into the following groups: control, control plus exercise, chemobrain, and chemobrain plus exercise. For chemobrain induction, 2 mg/kg of doxorubicin (DOX) a widely utilized chemotherapeutic agent among patients with breast cancer was dissolved in saline and directly injected to the abdomen once every 4 weeks. The exercise groups were subjected to low-intensity treadmill, 6 days per week for 4 weeks. The Morris water maze and step-down avoidance tests were conducted to evaluate cognitive function, while neuroplasticity and mitochondrial function were assessed in the hippocampus and dentate gyrus. Decreased cognitive function were observed in the chemobrain group, along with decreases in levels of neurogenesis, brain derived neurotrophic factor (BDNF), tropomyosin-related kinase B (TrkB), Ca(2+) retention in hippocampus. Rats of the chemobrain group also exhibited an increase in apoptosis, H(2)O(2) emission and permeability transition pore by hippocampal mitochondria. However, exercise attenuated impairments in cognitive function, neuroplasticity, and mitochondrial function induced by DOX treatment. Therefore, the findings of the present study indicate that low-intensity exercise may assist in preventing cognitive dysfunction during or after chemotherapy in patients with various cancers, including breast cancer. CI - Copyright (c) 2018 Elsevier Ltd. All rights reserved. FAU - Park, Hye-Sang AU - Park HS AD - Department of Physiology, College of Medicine, KyungHee University, Seoul, Republic of Korea. FAU - Kim, Chang-Ju AU - Kim CJ AD - Department of Physiology, College of Medicine, KyungHee University, Seoul, Republic of Korea. FAU - Kwak, Hyo-Bum AU - Kwak HB AD - Department of Kinesiology, Art & Sports, InHa University, Incheon, Republic of Korea. FAU - No, Mi-Hyun AU - No MH AD - Department of Kinesiology, Art & Sports, InHa University, Incheon, Republic of Korea. FAU - Heo, Jun-Won AU - Heo JW AD - Department of Kinesiology, Art & Sports, InHa University, Incheon, Republic of Korea. FAU - Kim, Tae-Woon AU - Kim TW AD - Department of Physiology, College of Medicine, KyungHee University, Seoul, Republic of Korea; Exercise Rehabilitation Research Institute, Department of Exercise & Health Science, SangMyung University, Seoul, Republic of Korea. Electronic address: twkim0806@naver.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Neuropharmacology JT - Neuropharmacology JID - 0236217 RN - 0 (Antibiotics, Antineoplastic) RN - 0 (Doublecortin Domain Proteins) RN - 0 (Microtubule-Associated Proteins) RN - 0 (Nerve Tissue Proteins) RN - 0 (Neuropeptides) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (bcl-2-Associated X Protein) RN - 80168379AG (Doxorubicin) RN - 9007-43-6 (Cytochromes c) RN - BBX060AN9V (Hydrogen Peroxide) RN - EC 3.4.22.- (Caspase 3) RN - G34N38R2N1 (Bromodeoxyuridine) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Antibiotics, Antineoplastic/*toxicity MH - Avoidance Learning/drug effects/physiology MH - Bromodeoxyuridine/metabolism MH - Calcium/metabolism MH - Caspase 3/metabolism MH - *Cognition Disorders/chemically induced/pathology/prevention & control MH - Cytochromes c/metabolism MH - Disease Models, Animal MH - Doublecortin Domain Proteins MH - Doxorubicin/*toxicity MH - Hippocampus/*drug effects MH - Hydrogen Peroxide/metabolism MH - In Situ Nick-End Labeling MH - Male MH - Maze Learning/drug effects/physiology MH - Microtubule-Associated Proteins/metabolism MH - Mitochondria/*drug effects/pathology MH - Nerve Tissue Proteins/metabolism MH - Neuronal Plasticity/*drug effects/physiology MH - Neuropeptides/metabolism MH - Physical Conditioning, Animal/*methods MH - Proto-Oncogene Proteins c-bcl-2/metabolism MH - Rats MH - Rats, Wistar MH - Time Factors MH - bcl-2-Associated X Protein/metabolism OTO - NOTNLM OT - Chemobrain OT - Cognitive function OT - Exercise OT - Hippocampus OT - Mitochondria OT - Neuroplasticity EDAT- 2018/02/27 06:00 MHDA- 2018/11/06 06:00 CRDT- 2018/02/26 06:00 PHST- 2017/08/05 00:00 [received] PHST- 2018/02/12 00:00 [revised] PHST- 2018/02/15 00:00 [accepted] PHST- 2018/02/27 06:00 [pubmed] PHST- 2018/11/06 06:00 [medline] PHST- 2018/02/26 06:00 [entrez] AID - S0028-3908(18)30070-4 [pii] AID - 10.1016/j.neuropharm.2018.02.013 [doi] PST - ppublish SO - Neuropharmacology. 2018 May 1;133:451-461. doi: 10.1016/j.neuropharm.2018.02.013.