期刊
JOURNAL OF NEUROENDOCRINOLOGY
卷 34, 期 7, 页码 -出版社
WILEY
DOI: 10.1111/jne.13166
关键词
astrocyte; cardiovascular; glia; hippocampus; hypothalamus; oxytocin
资金
- Deutsche Forschungsgemeinschaft Postdoc Fellowship [AL 2466/1-1]
- National Heart, Lung, and Blood Institute [NIH HL090948, NIH NS094640]
- Center for Neuroinflammation and Cardiometabolic Diseases (CNCD) at the Georgia State University
- German Research Foundation (DFG) [GR 3619/13-1, GR 3619/15-1, GR 3619/16-1]
- SFB Consortium [1158-2]
Oxytocin plays an important role in neuromodulation, memory processing, and social recognition in the hippocampal CA2 region. This study identified the paraventricular nucleus (PVN) as a major source of oxytocinergic innervation to CA2, with a high expression of oxytocin receptors (OTRs) in CA2 astrocytes. In a heart failure rat model, alterations in the PVN-to-CA2 oxytocinergic system were observed, which may contribute to cognitive and mood impairments.
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 (similar to 15%), this expression was much more abundant in CA2 astrocytes (similar to 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据