Effects of AraC treatment on motor coordination and cerebellar cytoarchitecture in the adult rat. A possible protective role of NAC.
Intact cerebellum cytoarchitecture and cellular communication are indispensable for successful motor coordination and certain forms of memory. Cytosine arabinoside (AraC), often used as an anti-neoplastic agent in humans, can have cerebellum-targeting adverse effects. In order to characterize the nature of AraC-induced cerebellar lesions in an adult rodent model, we have administered AraC (400 mg/kg b.w., i.p.) in adult male Wistar rats for 5 days. The animals' walking pattern, motor coordination, locomotion, spatial navigation and cognition were evaluated, along with neurofilament- and calbindin-like distribution in the cerebellum. AraC-treated rats demonstrated a disturbed walking pattern and a reduced ability of motor learning and coordination, indicative of a mild cerebellar deficit. Although the general locomotion and spatial cognition of AraC-treated rats was not significantly altered, their navigation into the water, in terms of swimming velocity, was irregular, compared to vehicle-treated animals. Neurofilament-like immunostaining was reduced in the molecular cerebellar layer, while calbindin D 28 kDa levels were increased in Purkinje neurons, following AraC treatment. Administration of the antioxidant N-acetylcysteine (NAC) (200 mg/kg b.w., p.o.), for 14 days (prior to and during AraC treatment) largely prevented the AraC-induced behavioral deficits. Our in vivo model of neurotoxicity provides data on the AraC-induced behavioral and cellular alterations concerning the adult rat cerebellum. Furthermore, it provides evidence of a possible neuroprophylactic role of the antioxidant N-acetylcysteine in this model of chemotherapy-induced toxicity.
Koros
Christos
C
Laboratory of Histology and Embryology, Athens University Medical School, Athens, Greece. pireas03@yahoo.gr
Papalexi
Eugenia
E
Anastasopoulos
Dimitrios
D
Kittas
Christos
C
Kitraki
Efthimia
E
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism; D002531:Cerebellum / Q000166:cytology* / Q000187:drug effects; D003071:Cognition / Q000187:drug effects; D003561:Cytarabine / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D003599:Cytoskeleton / Q000187:drug effects / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D016900:Neurofilament Proteins / Q000378:metabolism; D018696:Neuroprotective Agents; D004856:Postural Balance / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013028:Space Perception / Q000187:drug effects; D016138:Walking
D000964:Antimetabolites, Antineoplastic; D016900:Neurofilament Proteins; D018696:Neuroprotective Agents; D003561:Cytarabine; D002118:Calcium; D000111:Acetylcysteine