Increased levels of hexacosanoic acid in the brain of Winstar rats: a behavioral study
Clin. biomed. res
; 40(3): 161-166, 2020. graf
Article
在 En
| LILACS
| ID: biblio-1248278
Responsible library:
BR18.1
ABSTRACT
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 (C260) accumulation represents a hallmark in the pathogenesis of this disease. In this study, we examined whether an overload of C260 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 C260 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 C260 administration presented fewer crossings and rearing episodes and a higher latency to move 45 minutes after C260 injection. The present work yields experimental evidence that C260, 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 C260 accumulation and locomotor impairment in patients with X-ALD. (AU)Key words