Effect of l-Dopa in acute temozolomide-induced cognitive impairment in male mice: a possible antineuroinflammatory role

Abstract

Temozolomide is used commonly in the treatment of some types of cancers, but it may also result in cognitive impairments such as memory deficits. l-Dopa, a well known medicine for the central nervous system, has been shown to have positive effects on some cognitive disorders. Here we sought to investigate the effect of l-Dopa on temozolomide-induced cognitive impairments. BALB/c mice were subjected to 3-days temozolomide and 6-days concomitant l-Dopa/benserazide administration in six groups (control, l-Dopa 25 mg/kg, l-Dopa 75 mg/kg, temozolomide, temozolomide + l-Dopa 25 mg/kg, and temozolomide + l-Dopa 75 mg/kg). Open field test, object location recognition, novel object recognition test, and shuttle-box test were carried out to determine the locomotor, anxiety-like behavior, and memory function of subjects. TNF-α and brain-derived neurotrophic factor (BDNF) gene expression in the hippocampus was measured by real-time PCR. Mice treated with temozolomide showed recognition memory impairment, along with hippocampal TNF-α and BDNF mRNA expression level raise, and detection of histological insults in hematoxylin and eosin hippocampal slides. Mice that received temozolomide + l-Dopa showed normal behavioral function and lower TNF-α and BDNF hippocampal mRNA expression levels, and histologically normal hippocampal CA1 region in comparison with mice in the temozolomide group. Our results provide evidence that l-Dopa prevents temozolomide-induced recognition memory deficit in mice at the acute phase probably via l-Dopa antineuroinflammatory effects.