Increased levels of hexacosanoic acid in the brain of Wistar rats: a behavioral study

• Autor(a) principal: Marchetti, Desiree
• Data de Publicação: 2021
• Outros Autores: Coelho, Daniella de M, Coitinho, Adriana S, Guzzo, Edson F M, Padilha, Rafael B, Rosa, Gabriel de L, Vargas, Carmen R
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Clinical and Biomedical Research
• Texto Completo: https://seer.ufrgs.br/index.php/hcpa/article/view/103339
• topic: X-linked adrenoleukodystrophy; C26; Wistar rats; open field.

Introduction: X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal metabolic disorder associated with mutations in the ATP-binding cassette sub-family D member1 (ABCD1) 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.Methods: 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.Results: 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.Conclusion: 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.