TY - JOUR
T1 - Increased Levels of Circulating Methylglyoxal Have No Consequence for Cerebral Microvascular Integrity and Cognitive Function in Young Healthy Mice
AU - Berends, Eline
AU - Vangrieken, Philippe
AU - Amiri, Naima
AU - van de Waarenburg, Marjo P. H.
AU - Scheijen, Jean L. J. M.
AU - Hermes, Denise J. H. P.
AU - Wouters, Kristiaan
AU - van Oostenbrugge, Robert J.
AU - Schalkwijk, Casper G.
AU - Foulquier, Sebastien
PY - 2024/10/1
Y1 - 2024/10/1
N2 - Diabetes and other age-related diseases are associated with an increased risk of cognitive impairment, but the underlying mechanisms remain poorly understood. Methylglyoxal (MGO), a by-product of glycolysis and a major precursor in the formation of advanced glycation end-products (AGEs), is increased in individuals with diabetes and other age-related diseases and is associated with microvascular dysfunction. We now investigated whether increased levels of circulating MGO can lead to cerebral microvascular dysfunction, blood-brain barrier (BBB) dysfunction, and cognitive impairment. Mice were supplemented or not with 50 mM MGO in drinking water for 13 weeks. Plasma and cortical MGO and MGO-derived AGEs were measured with UPLC-MS/MS. Peripheral and cerebral microvascular integrity and inflammation were investigated. Cerebral blood flow and neurovascular coupling were investigated with laser speckle contrast imaging, and cognitive tests were performed. We found a 2-fold increase in plasma MGO and an increase in MGO-derived AGEs in plasma and cortex. Increased plasma MGO did not lead to cerebral microvascular dysfunction, inflammation, or cognitive decline. This study shows that increased concentrations of plasma MGO are not associated with cerebral microvascular dysfunction and cognitive impairment in healthy mice. Future research should focus on the role of endogenously formed MGO in cognitive impairment.
AB - Diabetes and other age-related diseases are associated with an increased risk of cognitive impairment, but the underlying mechanisms remain poorly understood. Methylglyoxal (MGO), a by-product of glycolysis and a major precursor in the formation of advanced glycation end-products (AGEs), is increased in individuals with diabetes and other age-related diseases and is associated with microvascular dysfunction. We now investigated whether increased levels of circulating MGO can lead to cerebral microvascular dysfunction, blood-brain barrier (BBB) dysfunction, and cognitive impairment. Mice were supplemented or not with 50 mM MGO in drinking water for 13 weeks. Plasma and cortical MGO and MGO-derived AGEs were measured with UPLC-MS/MS. Peripheral and cerebral microvascular integrity and inflammation were investigated. Cerebral blood flow and neurovascular coupling were investigated with laser speckle contrast imaging, and cognitive tests were performed. We found a 2-fold increase in plasma MGO and an increase in MGO-derived AGEs in plasma and cortex. Increased plasma MGO did not lead to cerebral microvascular dysfunction, inflammation, or cognitive decline. This study shows that increased concentrations of plasma MGO are not associated with cerebral microvascular dysfunction and cognitive impairment in healthy mice. Future research should focus on the role of endogenously formed MGO in cognitive impairment.
KW - Neurovascular coupling
KW - Cognitive function
KW - Advanced glycation endproducts
KW - Blood-brain barrier
KW - Methylglyoxal
KW - Glyoxalase 1
KW - DYSFUNCTION
KW - GLYCATION
KW - BARRIER
KW - STRESS
KW - IMPAIRMENT
KW - MEMORY
KW - MODEL
U2 - 10.1007/s12035-024-04552-3
DO - 10.1007/s12035-024-04552-3
M3 - Article
SN - 0893-7648
JO - Molecular Neurobiology
JF - Molecular Neurobiology
ER -