Sex-dependent behavioral alterations in BALB/c mouse bearing a non-CNS solid tumor.

Abstract

Background: Peripheral tumors can alter the central nervous system activity leading to behavior alterations and cancer-related cognitive impairment (CRCI). Although commonly attributed to anti-cancer treatments, findings of CRCI in newly diagnosed cancer patients suggest that tumors alone may impair brain functions, including working memory and processing speed.

Methods: We assessed male and female mice behavior using a novel object recognition and a Y maze test along with the open field and burrowing tests. The tests were performed before and after tumor implantation (subcutaneous murine L5178Y-R lymphoma injection in the posterior hind limb), and through its progression to evaluate mobility, anxiety, motivation recognition, and spatial working memory.

Results: Male mice showed deficits in recognition memory, scoring a low novel object time exploration (42.26% in males [p = 0.02] and 50.15% [p = 0.53] in females). Spontaneous alternation was significantly impaired in both male (p = 0.01) and female (p = 0.03) mice. During tumor progression, only female mice showed decreased mobility in indicators such as average speed, mobility rate, and total distance in the open field test, as well as deficient burrowing activity, indicating a lack of motivation or sickness behavior. Our findings suggest that tumor burden is associated with behavioral alterations in a sex-dependent manner in a mouse model of lymphoma.