Center for Neuroinflammation and Cardiometabolic Diseases, Georgia State University, Atlanta, Georgia, USA.
Department of Neuropeptide Research in Psychiatry, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany.
J Neuroendocrinol. 2022 Jul;34(7):e13166. doi: 10.1111/jne.13166. Epub 2022 Jun 3.
Oxytocinergic actions within the hippocampal CA2 are important for neuromodulation, memory processing and social recognition. However, the source of the OTergic innervation, the cellular targets expressing the OT receptors (OTRs) and whether the PVN-to-CA2 OTergic system is altered during heart failure (HF), a condition recently associated with cognitive and mood decline, remains unknown. Using immunohistochemistry along with retrograde monosynaptic tracing, RNAscope and a novel OTR-Cre rat line, we show that the PVN (but not the supraoptic nucleus) is an important source of OTergic innervation to the CA2. These OTergic fibers were found in many instances in close apposition to OTR expressing cells within the CA2. Interestingly, while only a small proportion of neurons were found to express OTRs (15%), this expression was much more abundant in CA2 astrocytes (40%), an even higher proportion that was recently reported for astrocytes in the central amygdala. Using an established ischemic rat heart failure (HF) model, we found that HF resulted in robust changes in the PVN-to-CA2 OTergic system, both at the source and target levels. Within the PVN, we found an increased OT immunoreactivity, along with a diminished OTR expression in PVN neurons. Within the CA2 of HF rats, we observed a blunted OTergic innervation, along with a diminished OTR expression, which appeared to be restricted to CA2 astrocytes. Taken together, our studies highlight astrocytes as key cellular targets mediating OTergic PVN inputs to the CA2 hippocampal region. Moreover, they provide the first evidence for an altered PVN-to-CA2 OTergic system in HF rats, which could potentially contribute to previously reported cognitive and mood impairments in this animal model.
海马 CA2 内的催产素能作用对于神经调节、记忆处理和社会认知很重要。然而，催产素能传入的来源、表达催产素受体（OTRs）的细胞靶标，以及在心力衰竭（HF）期间是否改变了室旁核到 CA2 的催产素能系统，这些问题仍然未知。HF 是一种与认知和情绪下降最近相关的疾病。利用免疫组织化学、逆行单突触追踪、RNAscope 和一种新型 OTR-Cre 大鼠品系，我们表明，PVN（而不是视上核）是 CA2 催产素能传入的重要来源。这些催产素能纤维在许多情况下与 CA2 内表达 OTR 的细胞紧密毗邻。有趣的是，虽然只有一小部分神经元被发现表达 OTRs（15%），但 CA2 星形胶质细胞中的表达更为丰富（40%），这一比例甚至比最近报道的中央杏仁核星形胶质细胞中的比例还要高。利用已建立的缺血性大鼠 HF 模型，我们发现 HF 导致了 PVN 到 CA2 的催产素能系统在源和靶水平上的强烈变化。在 PVN 中，我们发现 OT 免疫反应性增加，同时 PVN 神经元中的 OTR 表达减少。在 HF 大鼠的 CA2 中，我们观察到催产素能传入的减弱，以及 OTR 表达的减少，这似乎仅限于 CA2 星形胶质细胞。总之，我们的研究强调了星形胶质细胞作为介导 PVN 传入到 CA2 海马区的催产素能作用的关键细胞靶标。此外，它们提供了 HF 大鼠中改变的 PVN 到 CA2 催产素能系统的第一个证据，这可能有助于解释该动物模型中先前报道的认知和情绪障碍。
