Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Clinical and Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biosciences, State University of New York at Buffalo, Buffalo, NY, USA; Department of Psychology, State University at Buffalo, Buffalo, NY, USA.
Department of Nuclear Medicine, University at Buffalo, USA.
Psychiatry Res Neuroimaging. 2022 Jul;323:111486. doi: 10.1016/j.pscychresns.2022.111486. Epub 2022 Apr 26.
Fatty acid-binding proteins (FABPs) are intracellular chaperone proteins involved in the trafficking of n-3 polyunsaturated fatty acids and endocannabinoids. Inhibiting two of the main FABP subtypes found in the brain (FABP5 and FABP7) hinders endocannabinoid uptake and hydrolysis. Prior data indicates that cannabinoid receptor stimulation can ameliorate the consequences associated with chronic stress. To this end, FABP expression may play a similar role in response to stressful conditions. Male C57BL/6 J (WT) and FABP7 knockout (KO) mice were assigned to either a non-stress cohort or an unpredictable chronic mild stress (UCMS) cohort for a period of 4 weeks. Immediately after 4 weeks, mice were injected with [F]2-fluoro-2-deoxy-d-glucose (FDG) and scanned using micro positron emission tomography (mPET) to examine brain glucose metabolism (BGluM). WT mice exposed to UCMS showed reduced BGluM in striatal, cortical, and hypothalamic regions and showed increased BGluM in the hippocampus, thalamus, periaqueductal gray, superior colliculi, inferior colliculi, and cerebellum. In contrast, there were limited effects of UCMS on BGluM in FABP7 KO mice, with a reduction in the thalamus, periaqueductal gray, and superior colliculi. These findings provide novel insight into FABP7 expression and indicate this gene to play an important role in response to aversive stimuli.
脂肪酸结合蛋白(FABP)是一种细胞内伴侣蛋白,参与 n-3 多不饱和脂肪酸和内源性大麻素的转运。抑制大脑中两种主要的 FABP 亚型(FABP5 和 FABP7)会阻碍内源性大麻素的摄取和水解。先前的数据表明,大麻素受体的刺激可以改善与慢性应激相关的后果。为此,FABP 的表达可能在应对应激条件方面发挥类似的作用。雄性 C57BL/6J(WT)和 FABP7 敲除(KO)小鼠被分配到非应激队列或不可预测的慢性轻度应激(UCMS)队列中,为期 4 周。4 周后,立即给小鼠注射[F]2-氟-2-脱氧-d-葡萄糖(FDG),并用微正电子发射断层扫描(mPET)扫描,以检查大脑葡萄糖代谢(BGluM)。暴露于 UCMS 的 WT 小鼠显示纹状体、皮质和下丘脑区域的 BGluM 减少,而海马体、丘脑、中脑导水管周围灰质、上丘、下丘和小脑的 BGluM 增加。相比之下,UCMS 对 FABP7 KO 小鼠的 BGluM 影响有限,仅在丘脑、中脑导水管周围灰质和上丘减少。这些发现为 FABP7 表达提供了新的见解,并表明该基因在应对厌恶刺激方面发挥着重要作用。