Effects of leptin on neurocognitive and motor functions in juvenile rats in a preterm brain damage model

Abstract

Preterm infants face lifelong disabilities, including learning disorders, as well as visual, auditory and behavioral problems. Recent studies have demonstrated that leptin, an adipocytokine encoded by a gene associated with obesity and expressed in adipose tissue, affects neurocognitive and motor function; however, the mechanisms of brain damage in preterm infants are unclear. In the present study, the neuroprotective effects of leptin in a rat model of preterm hypoxic-ischemic brain damage were investigated. Rats (2-days-old) were subjected to brain damage (ligation of the common carotid artery followed by exposure to 6% oxygen for 2 h) and treated with vehicle (control) or leptin. Spatial memory was analyzed in the present study using the Morris water maze test 19 days following ligation. Over the 24-day post-surgical observation period, capture-resistance test, forelimb suspension and open field tests were conducted to evaluate motor function and anxiety-associated behavior. Treatment with leptin did not affect survival rate or body weight. Treatment with leptin increased the number of platform crossings in rats with premature brain damage in the Morris water maze test, which was used to assess spatial memory. Multivariate analysis revealed that leptin reduced the latency to finding the platform location, independent of gender and weight. In the capture-resistance, forelimb suspension and open field tests, there were no differences between animals administered leptin and the sham group. Collectively, the results of the present study suggested that leptin may alleviate spatial memory impairment resulting from premature brain damage, independent of gender or weight. These results may improve understanding of the neuroprotective effects exhibited by leptin in infants with preterm brain damage.