Chronic d-ribose and d-mannose overload induce depressive/anxiety-like behavior and spatial memory impairment in mice

Abstract

The effects of different forms of monosaccharides on the brain remain unclear, though neuropsychiatric disorders undergo changes in glucose metabolism. This study assessed cell viability responses to five commonly consumed monosaccharides—D-ribose (RIB), D-glucose, D-mannose (MAN), D-xylose and L-arabinose—in cultured neuro-2a cells. Markedly decreased cell viability was observed in cells treated with RIB and MAN. We then showed that high-dose administration of RIB induced depressive- and anxiety-like behavior as well as spatial memory impairment in mice, while high-dose administration of MAN induced anxiety-like behavior and spatial memory impairment only. Moreover, significant pathological changes were observed in the hippocampus of high-dose RIB-treated mice by hematoxylin-eosin staining. Association analysis of the metabolome and transcriptome suggested that the anxiety-like behavior and spatial memory impairment induced by RIB and MAN may be attributed to the changes in four metabolites and 81 genes in the hippocampus, which is involved in amino acid metabolism and serotonin transport. In addition, combined with previous genome-wide association studies on depression, a correlation was found between the levels of Tnni3k and Tbx1 in the hippocampus and RIB induced depressive-like behavior. Finally, metabolite–gene network, qRT-PCR and western blot analysis showed that the insulin-POMC-MEK-TCF7L2 and MAPK-CREB-GRIN2A-CaMKII signaling pathways were respectively associated with RIB and MAN induced depressive/anxiety-like behavior and spatial memory impairment. Our findings clarified our understanding of the biological mechanisms underlying RIB and MAN induced depressive/anxiety-like behavior and spatial memory impairment in mice and highlighted the deleterious effects of high-dose RIB and MAN as long-term energy sources.

MANF/EWSR1/ANXA6 pathway might as the bridge between hypolipidemia and major depressive disorder

“…Peripheral whole-blood samples were collected from each participant by venous puncture. Consistent with our previous study [ 28 ], serum was isolated by centrifugation at room temperature at 3000 × g for 15 min, aliquoted, and stored at −80 °C until use. Total MANF, EWSR1, and ANXA6 were measured using commercially available high-sensitivity ELISA kits from MEIMIAN (Jiangsu, China) by two blind experimenters.…”

OGDHL Variant rs2293239: A Potential Genetic Driver of Chinese Familial Depressive Disorder

“…TBX1 is responsible for most of the physical malformations present in 22q11.2 deletion syndrome, or DiGeorge syndrome, which is a congenital disease that has been implicated in various behavioral abnormalities including schizophrenia and other neuropsychiatric/behavioral disorders (69)(70)(71). A recent study also reported that TBX1 in the mouse hippocampus might be linked to monosaccharides-D-ribose-induced depressive-like behavior (72). In the present study, the rare variant rs41298838 was predicted to be highly deleterious to TBX1 function, which made it a potential driving variant for familial depression.…”

Ribose Intake as Food Integrator: Is It a Really Convenient Practice?

“…Thus, neuronal Tau-protein, α-synuclein, β2-microglobulin, following glycation, contribute to the development of several common neurodegenerative diseases [ 119 , 120 , 121 , 122 , 123 , 124 ]. In addition, cognitive impairments observed in animal models and in diabetic patients has been ascribed to glycation and AGEs accumulation linked to ribose [ 93 , 125 , 126 , 127 , 128 , 129 , 130 ]. Diabetic nephropathy also appears linked to glycation processes and AGEs accumulation [ 131 , 132 , 133 ].…”