Cyclophosphamide impairs hippocampus-dependent learning and memory in adult mice: Possible involvement of hippocampal neurogenesis in chemotherapy-induced memory deficits.
Cyclophosphamide (CYP) is an anti-neoplastic agent as well as an immunosuppressive agent. In order to elucidate the alteration in adult hippocampal function following acute CYP treatment, hippocampus-related behavioral dysfunction and changes in adult hippocampal neurogenesis in CYP-treated (intraperitoneally, 40 mg/kg) mice (8-10-week-old ICR) were analyzed using hippocampus-dependent learning and memory tasks (passive avoidance and object recognition memory test) and immunohistochemical markers of neurogenesis (Ki-67 and doublecortin (DCX)). Compared to the vehicle-treated controls, mice trained at 12h after CYP injection showed significant memory deficits in passive avoidance and the object recognition memory test. The number of Ki-67- and DCX-positive cells began to decrease significantly at 12h post-injection, reaching the lowest level at 24h after CYP injection; however, this reverted gradually to the vehicle-treated control level between 2 and 10 days. We suggest that the administration of a chemotherapeutic agent in adult mice interrupts hippocampal functions, including learning and memory, possibly through the suppression of hippocampal neurogenesis.
Yang
Miyoung
M
College of Veterinary Medicine, Chonnam National University and Animal Medical Institute, Gwangju 500-757, South Korea.
Kim
Joong-Sun
JS
Song
Myoung-Sub
MS
Kim
Sung-Ho
SH
Kang
Seong Soo
SS
Bae
Chun-Sik
CS
Kim
Jong-Choon
JC
Wang
Hongbing
H
Shin
Taekyun
T
Moon
Changjong
C
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D003520:Cyclophosphamide / Q000009:adverse effects / Q000494:pharmacology*; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D019394:Ki-67 Antigen / Q000378:metabolism; D007858:Learning / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects* / Q000502:physiology; D009479:Neuropeptides / Q000378:metabolism; D009483:Neuropsychological Tests; D046709:Pattern Recognition, Physiological / Q000187:drug effects / Q000502:physiology; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
D018906:Antineoplastic Agents, Alkylating; C000714847:Dcx protein, mouse; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; C498355:Mki67 protein, mouse; D009479:Neuropeptides; D003520:Cyclophosphamide