Reduction of oxytocin-containing neurons and enhanced glymphatic activity in the hypothalamic paraventricular nucleus of patients with type 2 diabetes mellitus
Abstract Evidence from animal experiments has shown that the hypothalamic paraventricular nucleus (PVN) plays a key role in regulating body weight and blood glucose levels. However, it is unclear whether neuron populations in the human PVN are involved in the development of type 2 diabetes mellitus...
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| Format: | Article |
| Language: | English |
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BMC
2023-07-01
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| Series: | Acta Neuropathologica Communications |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40478-023-01606-w |
| _version_ | 1797784356104699904 |
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| author | Felipe Correa-da-Silva Martin J. Kalsbeek Femke S. Gadella Jorn Oppersma Wei Jiang Samantha E. C. Wolff Nikita L. Korpel Dick F. Swaab Eric Fliers Andries Kalsbeek Chun-Xia Yi |
| author_facet | Felipe Correa-da-Silva Martin J. Kalsbeek Femke S. Gadella Jorn Oppersma Wei Jiang Samantha E. C. Wolff Nikita L. Korpel Dick F. Swaab Eric Fliers Andries Kalsbeek Chun-Xia Yi |
| author_sort | Felipe Correa-da-Silva |
| collection | DOAJ |
| description | Abstract Evidence from animal experiments has shown that the hypothalamic paraventricular nucleus (PVN) plays a key role in regulating body weight and blood glucose levels. However, it is unclear whether neuron populations in the human PVN are involved in the development of type 2 diabetes mellitus (T2DM). To address this, we investigated the neuronal and glial populations in the PVN of 26 T2DM patients and 20 matched controls. Our findings revealed a significant reduction in oxytocin (Oxt) neuron density in the PVN of T2DM patients compared to controls, while other neuronal populations remained unchanged. This suggests that Oxt neurons may play a specific role in the pathophysiology of T2DM. Interestingly, the reduction in Oxt neurons was accompanied by a decreased melanocortinergic input in to the PVN as reflected by a reduction in alpha-MSH immunoreactivity. We also analysed two glial cell populations, as they are important for maintaining a healthy neural microenvironment. We found that microglial density, phagocytic capacity, and their proximity to neurons were not altered in T2DM patients, indicating that the loss of Oxt neurons is independent of changes in microglial immunity. However, we did observe a reduction in the number of astrocytes, which are crucial for providing trophic support to local neurons. Moreover, a specific subpopulation of astrocytes characterized by aquaporin 4 expression was overrepresented in T2DM patients. Since this subset of astrocytes is linked to the glymphatic system, their overrepresentation might point to alterations in the hypothalamic waste clearance system in T2DM. Our study shows selective loss of Oxt neurons in the PVN of T2DM individuals in association with astrocytic reduction and gliovascular remodelling. Therefore, hypothalamic Oxt neurons may represent a potential target for T2DM treatment modalities. |
| first_indexed | 2024-03-13T00:38:42Z |
| format | Article |
| id | doaj.art-6857b8695bea4e418b99582681d471fb |
| institution | Directory Open Access Journal |
| issn | 2051-5960 |
| language | English |
| last_indexed | 2024-03-13T00:38:42Z |
| publishDate | 2023-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj.art-6857b8695bea4e418b99582681d471fb2023-07-09T11:27:40ZengBMCActa Neuropathologica Communications2051-59602023-07-0111111310.1186/s40478-023-01606-wReduction of oxytocin-containing neurons and enhanced glymphatic activity in the hypothalamic paraventricular nucleus of patients with type 2 diabetes mellitusFelipe Correa-da-Silva0Martin J. Kalsbeek1Femke S. Gadella2Jorn Oppersma3Wei Jiang4Samantha E. C. Wolff5Nikita L. Korpel6Dick F. Swaab7Eric Fliers8Andries Kalsbeek9Chun-Xia Yi10Department of Endocrinology and Metabolism, Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam University Medical Centers, Location AMC, University of AmsterdamDepartment of Endocrinology and Metabolism, Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam University Medical Centers, Location AMC, University of AmsterdamDepartment of Endocrinology and Metabolism, Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam University Medical Centers, Location AMC, University of AmsterdamDepartment of Endocrinology and Metabolism, Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam University Medical Centers, Location AMC, University of AmsterdamDepartment of Endocrinology and Metabolism, Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam University Medical Centers, Location AMC, University of AmsterdamDepartment of Endocrinology and Metabolism, Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam University Medical Centers, Location AMC, University of AmsterdamLaboratory of Endocrinology, Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam University Medical Centers, Location AMC, University of AmsterdamNetherlands Institute for NeuroscienceDepartment of Endocrinology and Metabolism, Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam University Medical Centers, Location AMC, University of AmsterdamDepartment of Endocrinology and Metabolism, Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam University Medical Centers, Location AMC, University of AmsterdamDepartment of Endocrinology and Metabolism, Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam University Medical Centers, Location AMC, University of AmsterdamAbstract Evidence from animal experiments has shown that the hypothalamic paraventricular nucleus (PVN) plays a key role in regulating body weight and blood glucose levels. However, it is unclear whether neuron populations in the human PVN are involved in the development of type 2 diabetes mellitus (T2DM). To address this, we investigated the neuronal and glial populations in the PVN of 26 T2DM patients and 20 matched controls. Our findings revealed a significant reduction in oxytocin (Oxt) neuron density in the PVN of T2DM patients compared to controls, while other neuronal populations remained unchanged. This suggests that Oxt neurons may play a specific role in the pathophysiology of T2DM. Interestingly, the reduction in Oxt neurons was accompanied by a decreased melanocortinergic input in to the PVN as reflected by a reduction in alpha-MSH immunoreactivity. We also analysed two glial cell populations, as they are important for maintaining a healthy neural microenvironment. We found that microglial density, phagocytic capacity, and their proximity to neurons were not altered in T2DM patients, indicating that the loss of Oxt neurons is independent of changes in microglial immunity. However, we did observe a reduction in the number of astrocytes, which are crucial for providing trophic support to local neurons. Moreover, a specific subpopulation of astrocytes characterized by aquaporin 4 expression was overrepresented in T2DM patients. Since this subset of astrocytes is linked to the glymphatic system, their overrepresentation might point to alterations in the hypothalamic waste clearance system in T2DM. Our study shows selective loss of Oxt neurons in the PVN of T2DM individuals in association with astrocytic reduction and gliovascular remodelling. Therefore, hypothalamic Oxt neurons may represent a potential target for T2DM treatment modalities.https://doi.org/10.1186/s40478-023-01606-wHypothalamusOxytocinType 2 diabetes mellitusAstrocytesGlymphaticInsulin resistance |
| spellingShingle | Felipe Correa-da-Silva Martin J. Kalsbeek Femke S. Gadella Jorn Oppersma Wei Jiang Samantha E. C. Wolff Nikita L. Korpel Dick F. Swaab Eric Fliers Andries Kalsbeek Chun-Xia Yi Reduction of oxytocin-containing neurons and enhanced glymphatic activity in the hypothalamic paraventricular nucleus of patients with type 2 diabetes mellitus Acta Neuropathologica Communications Hypothalamus Oxytocin Type 2 diabetes mellitus Astrocytes Glymphatic Insulin resistance |
| title | Reduction of oxytocin-containing neurons and enhanced glymphatic activity in the hypothalamic paraventricular nucleus of patients with type 2 diabetes mellitus |
| title_full | Reduction of oxytocin-containing neurons and enhanced glymphatic activity in the hypothalamic paraventricular nucleus of patients with type 2 diabetes mellitus |
| title_fullStr | Reduction of oxytocin-containing neurons and enhanced glymphatic activity in the hypothalamic paraventricular nucleus of patients with type 2 diabetes mellitus |
| title_full_unstemmed | Reduction of oxytocin-containing neurons and enhanced glymphatic activity in the hypothalamic paraventricular nucleus of patients with type 2 diabetes mellitus |
| title_short | Reduction of oxytocin-containing neurons and enhanced glymphatic activity in the hypothalamic paraventricular nucleus of patients with type 2 diabetes mellitus |
| title_sort | reduction of oxytocin containing neurons and enhanced glymphatic activity in the hypothalamic paraventricular nucleus of patients with type 2 diabetes mellitus |
| topic | Hypothalamus Oxytocin Type 2 diabetes mellitus Astrocytes Glymphatic Insulin resistance |
| url | https://doi.org/10.1186/s40478-023-01606-w |
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