TY - JOUR AU - Marchetti, Desiree AU - Coelho, Daniella de M AU - Coitinho, Adriana S AU - Guzzo, Edson F M AU - Padilha, Rafael B AU - Rosa, Gabriel de L AU - Vargas, Carmen R PY - 2021/03/11 Y2 - 2024/03/28 TI - Increased levels of hexacosanoic acid in the brain of Wistar rats: a behavioral study JF - Clinical and Biomedical Research JA - Clin Biomed Res VL - 40 IS - 3 SE - Artigos Originais DO - UR - https://seer.ufrgs.br/index.php/hcpa/article/view/103339 SP - AB - <p><strong>Introduction:</strong> X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal metabolic disorder associated with mutations in the ATP-binding cassette sub-family D member1 (<em>ABCD1</em>) gene. Practically all male patients with X-ALD develop adrenocortical insufficiency during childhood and progressive myelopathy and peripheral neuropathy in adulthood. However, some male patients develop a fatal cerebral demyelinating disease named cerebral adrenoleukodystrophy. Although the exact mechanisms underlying brain damage in X-ALD are still poorly elucidated, it is known that hexacosanoic acid (C26:0) accumulation represents a hallmark in the pathogenesis of this disease. In this study, we examined whether an overload of C26:0 injected in Wistar rats was capable of causing behavioral changes in these animals.</p><p><strong>Methods:</strong> Egg lecithin in ethanol was dried under a nitrogen stream and mixed with C26:0 methyl ester. Male Wistar rats at 2–3 weeks of age were obtained from Universidade Federal do Rio Grande do Sul (UFRGS), divided into 8 groups, and submitted to an open field test. We then analyzed line crossings (locomotion and exploration), rearing (orienting and investigatory responses), grooming (anxiety manifestation), and latency to move for each animal.</p><p><strong>Results:</strong> Animals subjected to C26:0 administration presented fewer crossings and rearing episodes and a higher latency to move 45 minutes after C26:0 injection. The present work yields experimental evidence that C26:0, the main accumulated metabolite in X-ALD, can cause behavioral alterations in rats such as the impairment of locomotion and exploratory capabilities, as well as a reduction in orienting and investigatory responses.</p><p><strong>Conclusion:</strong> Although our results are preliminary, they are extremely important for future studies that investigate C26:0 accumulation and locomotor impairment in patients with X-ALD.</p> ER -