Orexin-1 receptor expression after global ischemia in mice
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Tomoya Nakamachi1, Sakura Endo, Hirokazu Ohtaki
1Department of Anatomy, Showa University School of Medicine, Shinagawa-Ku, Tokyo 142-8555, Japan.
Abstract:
Orexins are neuropeptides that have a range of physiological effects including the regulation of feeding behavior and the sleep-wakefulness cycle. Recently, we reported that level of orexin A in spinal fluid was decreased in the patients of some neurodegenerative diseases and it is considered that orexin A and the receptors might be related to central nervous system disorders. However, the expression and localization of orexin receptors is not elicited well. Therefore, the purpose of this study is to investigate the time-dependent changes and the cellular localization of orexin receptor focusing on orexin-1 receptor (OX1R) in the mouse brain after transient common carotid artery occlusion (tCCAO) model by using immunohistochemical techniques. OX1R immunoreactivity dramatically increased and peaked in the hippocampus and cortex 2 days after tCCAO, but remained unchanged in the hypothalamus. Using double-immunohistochemistry, the OX1R immunopositive cells at 2 days after tCCAO were co-localized not only with neuronal marker, NeuN-immunoreactivity but also with astroglial and oligodendroglial markers, GFAP- and CNPase-immunoreactivities, respectively. These results suggested that OX1R is induced other cells in addition to the neurons during stress such as ischemia and orexins and its receptor might play an important role for ischemic insult.
Insights
Orexin-1 receptors (OX1R) increase in the mouse brain after ischemic stroke, appearing in neurons and glial cells. This suggests orexins and OX1R play a role in the brain
Area of Science:
- Neuroscience
- Neurobiology
- Ischemic Stroke Research
Background:
- Orexins regulate feeding and sleep-wake cycles.
- Decreased orexin A in cerebrospinal fluid is linked to neurodegenerative diseases.
- Orexin receptor expression and localization in the central nervous system are not well understood.
Purpose of the Study:
- Investigate time-dependent changes in orexin-1 receptor (OX1R) expression and localization in the mouse brain.
- Examine OX1R cellular localization after transient common carotid artery occlusion (tCCAO).
Main Methods:
- Utilized immunohistochemical techniques in a mouse model of transient common carotid artery occlusion (tCCAO).
- Performed double-immunohistochemistry to identify OX1R co-localization with neuronal and glial markers.
Main Results:
- OX1R immunoreactivity significantly increased in the hippocampus and cortex 2 days post-tCCAO, peaking at this time.
- OX1R levels remained unchanged in the hypothalamus.
- OX1R-positive cells were found in neurons (NeuN+), astrocytes (GFAP+), and oligodendrocytes (CNPase+) 2 days after tCCAO.
Conclusions:
- OX1R is induced in non-neuronal cells, including astrocytes and oligodendrocytes, during ischemic stress.
- Orexins and their receptors may play a significant role in the response to ischemic insults.
- Findings highlight the involvement of the orexin system in the brain's reaction to ischemia.
