Involvement of Paired Immunoglobulin-like Receptor B in Diabetes-Associated Cognitive Dysfunction Through Modulation of Axon Outgrowth and Dendritic Remodeling.

Abstract

Type 2 diabetic patients have high risk of developing cognitive dysfunction, in which neural structural plasticity has played a pivotal role. Paired immunoglobulin-like receptor B (PirB), a receptor mainly expressed in neurons, acts as a critical inhibitor of neurite outgrowth and neural plasticity. However, the role of PirB in type 2 diabetes-associated cognitive dysfunction remains unknown. In this study, learning and memory impairment was observed in 24-week-old db/db mice by performing Morris water maze task, and the number of synapses along with the length of postsynaptic density by transmission electron microscopy were reduced in the hippocampus of db/db mice. Furthermore, PirB expression in the hippocampus of db/db mice was significantly upregulated using western blotting and immunofluorescence analysis. In cultured hippocampal neurons, high glucose treatment reduced the length of the longest neurite as well as axon initial segment (AIS), whereas silencing PirB expression rescued high glucose-induced neurite outgrowth inhibition, but not AIS. Additionally, cognitive deficits, dendrite morphology defects, and synapse-related proteins loss in db/db mice were alleviated when PirB knockdown was performed by adeno-associated virus injection. In conclusion, PirB is involved in diabetes-associated cognitive dysfunction through modulation of axon outgrowth and dendritic remodeling, providing a potential therapeutic target for diabetes-associated cognitive dysfunction.

• Authors: Kairui Pu, Meiyan Wu, Tao Jiang, Yuxin Zhang, Mao Ye, Jianyu Sun, Hongli Ma, Qian Zhai, Qiang Wang
• Journal: Molecular neurobiology (Mol Neurobiol) Vol. 59 Issue 4 Pg. 2563-2579 (Apr 2022) ISSN: 1559-1182 [Electronic] United States
• PMID: 35091963 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Immunoglobulins
• Pirb protein, mouse
• Receptors, Immunologic
• Glucose

Topics

• Animals
• Cognitive Dysfunction (metabolism)
• Diabetes Mellitus, Type 2
• Glucose
• Humans
• Immunoglobulins
• Mice
• Mice, Inbred Strains
• Neuronal Outgrowth
• Neuronal Plasticity (physiology)
• Receptors, Immunologic (metabolism)