Laboratory of Cellular and Molecular Neuroscience (LCMN), School of Life Science, Faculty of Science, University of Technology Sydney, PO Box 123 Broadway, Sydney, NSW, 2007, Australia.
Neural Injury Research Unit, School of Life Science, Faculty of Science, University of Technology Sydney, Sydney, NSW, Australia.
J Mol Neurosci. 2023 Oct;73(9-10):724-737. doi: 10.1007/s12031-023-02151-w. Epub 2023 Aug 30.
Previous evidence shows that rapid changes occur in the brain following spinal cord injury (SCI). Here, we interrogated the expression of the neuropeptides pituitary adenylyl cyclase-activating peptide (PACAP), vasoactive intestinal peptides (VIP), and their binding receptors in the rat brain 24 h following SCI. Female Sprague-Dawley rats underwent thoracic laminectomy; half of the rats received a mild contusion injury at the level of the T10 vertebrate (SCI group); the other half underwent sham surgery (sham group). Twenty-four hours post-surgery, the hypothalamus, thalamus, amygdala, hippocampus (dorsal and ventral), prefrontal cortex, and periaqueductal gray were collected. PACAP, VIP, PAC1, VPAC1, and VPAC2 mRNA and protein levels were measured by real-time quantitative polymerase chain reaction and Western blot. In SCI rats, PACAP expression was increased in the hypothalamus (104-141% vs sham) and amygdala (138-350%), but downregulated in the thalamus (35-95%) and periaqueductal gray (58-68%). VIP expression was increased only in the thalamus (175-385%), with a reduction in the amygdala (51-68%), hippocampus (40-75%), and periaqueductal gray (74-76%). The expression of the PAC1 receptor was the least disturbed by SCI, with decrease expression in the ventral hippocampus (63-68%) only. The expression levels of VPAC1 and VPAC2 receptors were globally reduced, with more prominent reductions of VPAC1 vs VPAC2 in the amygdala (21-70%) and ventral hippocampus (72-75%). In addition, VPAC1 downregulation also extended to the dorsal hippocampus (69-70%). These findings demonstrate that as early as 24 h post-SCI, there are region-specific disruptions of PACAP, VIP, and related receptor transcript and protein levels in supraspinal regions controlling higher cognitive functions.
先前的证据表明，脊髓损伤（SCI）后大脑会发生迅速变化。在这里，我们研究了在 SCI 后 24 小时大鼠大脑中神经肽垂体腺苷酸环化酶激活肽（PACAP）、血管活性肠肽（VIP）及其结合受体的表达。雌性 Sprague-Dawley 大鼠行胸段椎板切除术；一半大鼠在 T10 椎体水平接受轻度挫伤性损伤（SCI 组）；另一半大鼠行假手术（假手术组）。术后 24 小时收集下丘脑、丘脑、杏仁核、海马（背侧和腹侧）、前额皮质和导水管周围灰质。通过实时定量聚合酶链反应和 Western blot 测量 PACAP、VIP、PAC1、VPAC1 和 VPAC2 mRNA 和蛋白水平。在 SCI 大鼠中，PACAP 表达在下丘脑（104-141% vs 假手术组）和杏仁核（138-350%）中增加，但在丘脑（35-95%）和导水管周围灰质（58-68%）中下调。VIP 表达仅在丘脑（175-385%）中增加，而在杏仁核（51-68%）、海马（40-75%）和导水管周围灰质（74-76%）中减少。PAC1 受体的表达受 SCI 的干扰最小，仅在腹侧海马中表达减少（63-68%）。VPAC1 和 VPAC2 受体的表达水平普遍降低，杏仁核（21-70%）和腹侧海马（72-75%）中 VPAC1 的降低更为明显，而腹侧海马（72-75%）中 VPAC2 的降低更为明显。此外，VPAC1 的下调也扩展到背侧海马（69-70%）。这些发现表明，早在 SCI 后 24 小时，控制高级认知功能的上位脑区中就存在 PACAP、VIP 及其相关受体转录本和蛋白水平的区域特异性破坏。
