Effects of perfluorooctanoic acid intraperitoneal exposures on neurobehavioral outcomes in C57Bl/6J mice

Abstract

Perfluorooctanoic acid (PFOA) is a substance with a long half-life in humans and other living organisms and has various toxic properties, including central nervous system toxicity. We investigated the neurotoxic effects of PFOA sub-acute exposure on occurrence of depressive-like behavior and memory impairment in mice. Experimental groups of C57BL/6J mice (total 84; 42 female, 42 male; n = 6 per group) included groups exposed to PFOA intraperitoneally (1, 5, 10, or 20 mg kg(-1) d(-1) for 14 d, and control groups left unexposed or administered PFOA carrier (vehicle) only. Behavioral tests assessing depressive-like behavior and memory included locomotor test, forced swim test (FST), object recognition test (ORT) with recognition index (RI), and novelty suppressed feeding test (NSFT). We examined the hippocampus region of mice to measure levels of 2-4-1-brain-derived neurotropic factor (BDNF) and tumor necrosis factor alpha (TNF alpha). With PFOA exposure, female mice lost more weight than males, particularly in the 20 mg kg(-1) group. Increased FST immobility time and decreased climbing time were observed in PFOA-exposed groups; immobility times in male mice receiving doses >= 5 mg kg(-1) and female mice receiving doses >= 1 mg kg(-1) were significantly higher compared to control groups (all P < 0.05). ORT learning time was significantly increased, and the RI was significantly reduced in PFOA-exposed mice compared to controls (all P < 0.05). NSFT demonstrated increased latency time in PFOA-exposed groups compared to controls (all P < 0.05). BDNF levels decreased and TNF alpha levels increased with PFOA exposure in male and female mice, with TNF alpha being significantly different between mice exposed to 20 mg kg(-1) PFOA and unexposed controls (males, mean +/- SEM 356.6 +/- 1.718 pg mg(-1) vs 6.75 +/- 1.631 pg mg(-1) in controls; females, 216.4 +/- 17.58 pg mg(-1) vs 8.623 +/- 0.68 pg mg(-1) in controls; each P < 0.001). Sub-acute exposure to PFOA appears to be associated with memory impairment and depressive-like behavior in C57BL/6J mice. Female mice showed more sensitivity to its neurotoxic effects, which may be related to hormonal changes. These findings need further evaluation.