Roszkowicz-Ostrowska Katarzyna, Młotkowska Patrycja, Marciniak Elżbieta, Szlis Michał, Barszcz Marcin, Misztal Tomasz
The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, Instytucka 3 Str., 05-110 Jabłonna, Poland.
Cells. 2024 Nov 21;13(23):1928. doi: 10.3390/cells13231928.
Fluctuations in kynurenic acid (KYNA) and brain-derived neurotrophic factor (BDNF) levels in the brain reflect its neurological status. The aim of the study was to investigate the effect of transiently elevated KYNA concentrations in the cerebroventricular circulation on the expression of BDNF and its high-affinity tropomyosin-related kinase receptor B (TrkB) in specific structures of the sheep brain. Intracerebroventricularly cannulated anestrous sheep were subjected to a series of four 30 min infusions of KYNA: 4 × 5 μg/60 μL/30 min (KYNA20, = 6) and 4 × 25 μg/60 μL/30 min (KYNA100, = 6) or a control infusion ( = 6), at 30 min intervals. Sections of the hippocampal CA3 field, amygdala (AMG), prefrontal cortex (PCx), and the hypothalamic medial-basal (MBH) and preoptic (POA) areas were dissected from the brain immediately after the experiment. The highest concentration of BDNF protein was found in the CA3 field ( < 0.001), which was 8-fold higher than in the AMG and 12-fold higher than that in the PCx (MBH and POA were not analyzed). The most pronounced BDNF mRNA expression was observed in the MBH, followed by the PCx, POA, AMG and CA3, while the highest abundance of TrkB mRNA was recorded in the AMG, followed by the MBH, PCx, CA3, and POA. KYNA increased ( < 0.05- < 0.01) BDNF protein levels and the expression of its gene in the brain structures were examined, with the effect varying by dose and brain region. KYNA, particularly at the KYNA100 dose, also increased ( < 0.01) gene expression, except for the AMG, where the lower KYNA20 dose was more effective ( < 0.01). These findings suggest a positive relationship between KYNA levels in the cerebroventricular circulation and BDNF-TrkB expression in specific brain regions in a sheep model. This indicates that a transient increase in the CSF KYNA concentration can potentially restore BDNF production, for which deficiency underlies numerous neurological disorders.
大脑中犬尿喹啉酸（KYNA）和脑源性神经营养因子（BDNF）水平的波动反映了其神经学状态。本研究的目的是探讨脑室循环中KYNA浓度短暂升高对绵羊大脑特定结构中BDNF及其高亲和力原肌球蛋白相关激酶受体B（TrkB）表达的影响。对脑室内插管的乏情绵羊进行一系列四次30分钟的KYNA输注：4×5μg/60μL/30分钟（KYNA20，n = 6）和4×25μg/60μL/30分钟（KYNA100，n = 6）或对照输注（n = 6），间隔30分钟。实验结束后立即从大脑中分离出海马CA3区、杏仁核（AMG）、前额叶皮质（PCx）以及下丘脑内侧基底部（MBH）和视前区（POA）的切片。在CA3区发现BDNF蛋白浓度最高（P<0.001），比AMG高8倍，比PCx高12倍（未分析MBH和POA）。在MBH中观察到最明显的BDNF mRNA表达，其次是PCx、POA、AMG和CA3，而TrkB mRNA丰度最高的是AMG，其次是MBH、PCx、CA3和POA。检测了KYNA对大脑结构中BDNF蛋白水平及其基因表达的影响（P<0.05 - P<0.01），其作用因剂量和脑区而异。KYNA，特别是在KYNA100剂量下，也增加了TrkB基因表达（P<0.01），但在AMG中，较低的KYNA20剂量更有效（P<0.01）。这些发现表明在绵羊模型中，脑室循环中KYNA水平与特定脑区中BDNF - TrkB表达之间存在正相关关系。这表明脑脊液中KYNA浓度的短暂升高可能潜在地恢复BDNF的产生，而BDNF缺乏是许多神经疾病的基础。
