Hyperglycemia induces RAGE-dependent hippocampal spatial memory impairments

• Published in: Physiology & behavior Vol. 229; p. 113287
• Main Authors: Momeni, Zeinab, Neapetung, Joseph, Pacholko, Anthony, Kiir, Tabitha Achan Bol, Yamamoto, Yasuhiko, Bekar, Lane K, Campanucci, Verónica A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-02-2021
• Subjects: Anxiety; Cognitive dysfunction; Locomotor activity; Metabolic disorder; Mouse model of STZ-induced hyperglycemia; Receptor for advanced glycation end products; Metabolic disorder; Anxiety; Receptor for advanced glycation end products; Mouse model of STZ-induced hyperglycemia; Cognitive dysfunction; Locomotor activity
• ISSN: 0031-9384; 1873-507X
• DOI: 10.1016/j.physbeh.2020.113287

•Diabetes has been shown to affect cognitive function such as learning and memory.•Role of RAGE it still unknown in diabetes-induced cognitive dysfunction.•We found that recognition memory was independent of RAGE in STZ-induced hyperglycemia.•Spatial memory, however, was dependent on RAGE in STZ-induced hyperglycemia.•We identified RAGE as a contributor to spatial memory impairment in hyperglycemic mice.
Diabetes is a prevalent metabolic disorder that has long been associated with changes in different regions of the brain, including the hippocampus. Changes in hippocampal synaptic plasticity and subsequent impairment in cognitive functions such as learning and memory, are well documented in animal models of type 1 and type 2 diabetes. It is known that RAGE contributes to peripheral micro- and macro-vascular complications of diabetes. However, it is still unknown if RAGE plays a similar role in the development of CNS complications of diabetes. Therefore, we hypothesize that RAGE contributes to cognitive dysfunction, such as learning and memory impairments, in a mouse model of STZ-induced hyperglycemia. Control and STZ-induced hyperglycemic mice from WT and RAGE-KO groups were used for the behavioral experiments. While STZ-induced hyperglycemia decreased locomotor activity in the open field (OF) test, it did not affect the recognition memory in the novel object recognition (NOR) test in either genotype. Spatial memory, however, was impaired in STZ-induced hyperglycemic mice in WT but not in RAGE-KO group in both the Barnes maze (BM) and the Morris water maze (MWM) tests. Consistently, the RAGE antagonist FPS-ZM1 protected WT STZ-induced hyperglycemic mice from spatial memory impairment in the BM test. Our findings indicate that the parameters associated with locomotor activity and recognition memory were independent of RAGE in STZ-induced hyperglycemic mice. In contrast, the parameters associated with hippocampal-dependent spatial memory were dependent on RAGE expression.