Spatial memory deficits after vincristine-induced lesions to the dorsal hippocampus

Abstract

Vincristine is a commonly used cytostatic drug for the treatment of leukemia, neuroblastoma and lung cancer, which is known to have neurotoxic properties. The aim of this study was to assess the effects of vincristine, injected directly into the dorsal hippocampus, in spatial memory using the spatial cone field discrimination task. Long Evans rats were trained in the cone field, and after reaching training criterion received bilateral vincristine infusions into the dorsal hippocampus. Vincristine-treated animals presented unilateral or bilateral hippocampal lesions. Animals with bilateral lesions showed lower spatial working and reference memory performance than control animals, but task motivation was unaffected by the lesions. Working and reference memory of animals with unilateral lesions did not differ from animals with bilateral lesions and control animals. In sum, intrahippocampal injection of vincristine caused profound tissue damage in the dorsal hippocampus, associated with substantial cognitive deficits.

An update on neurobiological mechanisms involved in the development of chemotherapy-induced cognitive impairment (CICI)

“…Further assays revealed that cytotoxicity was mediated by depolarization of the mitochondrial membrane potential after 48 h of exposure to chemotherapeutics [6] . Other studies have shown that another chemotherapeutic drug, vincristine, destroys hippocampal tissue when administered unilaterally or bilaterally to mice [60] .…”

Anorexia-Induced Hypoleptinemia Drives Adaptations in the JAK2/STAT3 Pathway in the Ventral and Dorsal Hippocampus of Female Rats

“…In particular, the vHip governs the overall affective state and moderates the effects of emotional experience and stress. The dHip, instead, is mainly involved in controlling cognitive functions, including memory, learning and spatial contextual detection [ 68 , 69 , 70 ]. In addition, both subregions are involved in delaying meal initiation and influencing the amount of food consumed [ 71 , 72 ].…”

Local production of reactive oxygen species drives vincristine-induced axon degeneration

“…Another type of neurological side effect of chemotherapeutics such as vincristine involves cognitive and memory deficits commonly referred to as chemo brain [ 4 – 6 ]. This suggests that central as well as peripheral neurons can be negatively affected by chemotherapy.…”