Histamine-3 Receptor Availability and Glutamate Levels in the Brain: A PET-1H-MRS Study of Patients With Schizophrenia and Healthy Controls.

IF 4.5 2区 医学 Q1 CLINICAL NEUROLOGY International Journal of Neuropsychopharmacology Pub Date : 2024-03-01 DOI:10.1093/ijnp/pyae011
Atheeshaan Arumuham, Matthew M Nour, Mattia Veronese, Katherine Beck, Ellis Chika Onwordi, David J Lythgoe, Sameer Jauhar, Eugenii A Rabiner, Oliver D Howes
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Abstract

Background: The histamine-3 receptor (H3R) may have a role in cognitive processes through its action as a presynaptic heteroreceptor inhibiting the release of glutamate in the brain. To explore this, we examined anterior cingulate cortex (ACC) and striatum H3R availability in patients with schizophrenia and characterized their relationships with glutamate levels in corresponding brain regions.

Methods: We employed a cross-sectional study, recruiting 12 patients with schizophrenia and 12 healthy volunteers. Participants underwent positron emission tomography using the H3R-specific radio ligand [11C]MK-8278, followed by proton magnetic resonance spectroscopy to measure glutamate levels, recorded as Glu and Glx. Based on existing literature, the ACC and striatum were selected as regions of interest.

Results: We found significant inverse relationships between tracer uptake and Glu (r = -0.66, P = .02) and Glx (r = -0.62, P = .04) levels in the ACC of patients, which were absent in healthy volunteers (Glu: r = -0.19, P = .56, Glx: r = 0.10, P = .75). We also found a significant difference in striatal (F1,20 = 6.00, P = .02) and ACC (F1,19 = 4.75, P = .04) Glx levels between groups.

Conclusions: These results provide evidence of a regionally specific relationship between H3Rs and glutamate levels, which builds on existing preclinical literature. Our findings add to a growing literature indicating H3Rs may be a promising treatment target in schizophrenia, particularly for cognitive impairment, which has been associated with altered glutamate signaling.

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组胺-3 受体在大脑中的可用性和谷氨酸水平:对精神分裂症患者和健康对照组的 PET-1H-MRS 研究。
背景:组胺-3受体(H3R)作为突触前异受体可抑制谷氨酸在大脑中的释放,从而可能在认知过程中发挥作用。为了探讨这一问题,我们研究了精神分裂症患者前扣带回皮层(ACC)和纹状体 H3R 的可用性,并分析了它们与相应脑区谷氨酸水平的关系:我们采用了一项横断面研究,招募了 12 名精神分裂症患者和 12 名健康志愿者。研究人员使用 H3R 特异性放射性配体 [11C]MK-8278 进行了正电子发射断层扫描(PET),随后使用质子磁共振波谱(1H-MRS)测量谷氨酸水平(以 Glu 和 Glx 表示)。根据现有文献,我们选择 ACC 和纹状体作为研究区域(ROI):结果:我们发现在患者的 ACC 中,示踪剂摄取与 Glu(r = -0.66,p = 0.02)和 Glx(r = -0.62,p = 0.04)水平之间存在明显的反比关系,而健康志愿者则没有这种关系(Glu:r = -0.19,p = 0.56;Glx:r = 0.10,p = 0.75)。我们还发现,不同组间纹状体(F1,20 = 6.00,p = 0.02)和ACC(F1,19 = 4.75,p = 0.04)的Glx水平存在明显差异:这些结果为 H3Rs 与谷氨酸水平之间的区域特异性关系提供了证据,这是在现有临床前文献的基础上得出的结论。越来越多的文献表明,H3Rs 可能是精神分裂症的一个有前途的治疗靶点,尤其是对认知障碍的治疗,而认知障碍与谷氨酸信号的改变有关。
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来源期刊
CiteScore
8.40
自引率
2.10%
发文量
230
审稿时长
4-8 weeks
期刊介绍: The central focus of the journal is on research that advances understanding of existing and new neuropsychopharmacological agents including their mode of action and clinical application or provides insights into the biological basis of psychiatric disorders and thereby advances their pharmacological treatment. Such research may derive from the full spectrum of biological and psychological fields of inquiry encompassing classical and novel techniques in neuropsychopharmacology as well as strategies such as neuroimaging, genetics, psychoneuroendocrinology and neuropsychology.
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