The opioid growth factor (OGF) is an endogenous peptide that binds to the nuclear-associated receptor (OGFr), and plays a significant role in the proliferation of developing, renewing, and healing tissues. The receptor is widely expressed in a variety of organs, however its distribution in the brain remains unknown. In this study, we investigated the distribution of OGFr in different brain regions of male heterozygous (-/+ Lepr ^db/J), non -diabetic mice and determined the localization of the receptor in three major brain cell types, astrocytes, microglia, and neurons. Immunofluorescence imaging revealed that the highest number of OGFr was in hippocampal CA3 subregion followed by primary motor cortex, hippocampal CA2, thalamus, caudate and hypothalamus in a descending order. Double immunostaining revealed receptor colocalization with neurons and little or no colocalization in microglia and astrocytes. The highest percentage of OGFr positive neurons was identified in the CA3. Hippocampal CA3 neurons play an important role in memory processing, learning and behavior, and motor cortex neurons are important for muscle movement. However, the significance of the OGFr receptor in these brain regions and its relevance in diseased conditions are not known. Our findings provide a basis for understanding the cellular target and interaction of the OGF- OGFr pathway in neurodegenerative diseases such as Alzheimer's, Parkinson's, and stroke where hippocampus and cortex have an important role. This foundational data may also be useful in drug discovery to modulate OGFr by opioid receptor antagonist in various CNS diseases.

阿片样生长因子 (OGF) 是一种内源性肽，可与核相关受体 (OGFr) 结合，在发育、更新和愈合组织的增殖中发挥重要作用。该受体在多种器官中广泛表达，但其在大脑中的分布仍然未知。^{在这项研究中，我们调查了 OGFr 在男性杂合子 (-/+ Lepr db)}不同脑区的分布 /J)、非糖尿病小鼠并确定受体在三种主要脑细胞类型、星形胶质细胞、小胶质细胞和神经元中的定位。免疫荧光成像显示，OGFr 数量最多的是海马 CA3 亚区，其次是初级运动皮层、海马 CA2、丘脑、尾状核和下丘脑，降序排列。双免疫染色显示受体与神经元共定位，在小胶质细胞和星形胶质细胞中很少或没有共定位。在 CA3 中发现了最高百分比的 OGFr 阳性神经元。海马 CA3 神经元在记忆处理、学习和行为中发挥重要作用，运动皮层神经元对肌肉运动很重要。然而，这些大脑区域中 OGFr 受体的重要性及其与疾病状况的相关性尚不清楚。我们的研究结果为理解 OGF-OGFr 通路在神经退行性疾病（例如阿尔茨海默氏症、帕金森氏症和中风，其中海马体和皮质具有重要作用）中的细胞靶标和相互作用提供了基础。该基础数据也可用于药物发现，以在各种中枢神经系统疾病中通过阿片受体拮抗剂调节 OGFr。