D-serine Ameliorates Motor and Cognitive Impairments in β-amyloid 1-42 Injected Mice by Inhibiting JNK Signaling Pathway

Liu, Hongqing; Li, Shiqi; Yang, Cuizhu; Jia, Hui; Gu, Ziting; Tu, Xing; Tian, Sumin; Liu, Jing; Li, Guoying; Ma, Yuxin

doi:10.1016/j.jchemneu.2020.101852

Cited by 14 publications

(9 citation statements)

References 51 publications

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“…Finally, it is possible that the age‐related decline in motor and cognitive impairment in the 5xFAD mice are intricately intertwined and caused by the degeneration of common neurochemical pathways and can not be dissociated: they are two aspects of the progression of AD 133 . Similar combinations of motor and cognitive deficits occur in Parkinson's disease 134–136 and Huntington's disease, 137 and it is possible that effective drug treatments will improve both motor and cognitive functions in the 5xFAD mice 138 …”

Section: Discussionmentioning

confidence: 99%

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Visuo‐spatial learning and memory impairments in the 5xFAD mouse model of Alzheimer's disease: Effects of age, sex, albinism, and motor impairments

Brown

2022

Genes Brain and Behavior

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The 5xFAD mouse model of Alzheimer's disease (AD) rapidly develops AD‐related neuro‐behavioral pathology. Learning and memory impairments in 5xFAD mice, however, are not always replicated and the size of impairments varies considerably across studies. To examine possible sources of this variability, we analyzed the effects of age, sex, albinism due to background genes (Tyrc, Oca2p) and motor impairment on learning and memory performance of wild type and 5xFAD mice on the Morris water maze, from 3 to 15 months of age. The 5xFAD mice showed impaired learning at 6–9 months of age, but memory impairments were not detected with the test procedure used in this study. Performance of 5xFAD mice was profoundly impaired at 12–15 months of age, but was accompanied by slower swim speeds than wild‐type mice and a frequent failure to locate the escape platform. Overall female mice performed worse than males, and reversal learning impairments in 5xFAD mice were more pronounced in females than males. Albino mice performed worse than pigmented mice, confirming that albinism can impair performance of 5xFAD mice independently of AD‐related transgenes. Overall, these results show that 5xFAD mice have impaired learning performance at 6–9 months of age, but learning and memory performance at 12–15 months is confounded with motor impairments. Furthermore, sex and albinism should be controlled to provide an accurate assessment of AD‐related transgenes on learning and memory. These results will help reduce variability across pre‐clinical experiments with 5xFAD mice, and thus enhance the reliability of studies developing new therapeutics for AD.

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Section: Discussionmentioning

confidence: 99%

“… 133 Similar combinations of motor and cognitive deficits occur in Parkinson's disease 134 , 135 , 136 and Huntington's disease, 137 and it is possible that effective drug treatments will improve both motor and cognitive functions in the 5xFAD mice. 138 …”

Section: Discussionmentioning

confidence: 99%

Visuo‐spatial learning and memory impairments in the 5xFAD mouse model of Alzheimer's disease: Effects of age, sex, albinism, and motor impairments

Brown

2022

Genes Brain and Behavior

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“…Whereas the levels of D-serine (an endogenous full agonist of the glycine site of NMDAR) were higher in the cerebrospinal fluid of the probable AD patients than in healthy controls ( Madeira et al, 2015 ), D-serine levels were lower in the serum of the AD patients ( Hashimoto et al, 2004 ). D-serine administration also improved spatial memory, learning, and problem solving in older adults ( Avellar et al, 2016 ) and alleviated the cognitive impairment of Aβ1-42 injected mice ( Liu et al, 2020 ). Moreover, the NMDAR density declined with age ( Segovia et al, 2001 ), and Aβ downregulated the surface expression of NMDARs ( Snyder et al, 2005 ; Kurup et al, 2010 ).…”

Section: Introductionmentioning

confidence: 99%

Blood D-Amino Acid Oxidase Levels Increased With Cognitive Decline Among People With Mild Cognitive Impairment: A Two-Year Prospective Study

Lin

Lane

2022

International Journal of Neuropsychopharmacology

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Background Dysregulation of N-methyl-D-aspartate receptor (NMDAR) neurotransmission has been reported to be implicated in the pathogenesis of Alzheimer’s disease (AD). D-amino acid oxidase (DAO), responsible for degradation of NMDAR-related D-amino acids such as D-serine, regulates NMDAR function. A cross-section study found that serum DAO levels were positively related with the severity of cognitive aging among elderly individuals. This 2-year prospective study aimed to explore the role of DAO levels in predicting the outcome of patients with the very early-phase AD, such as mild cognitive impairment (MCI). Methods Fifty-one patients with MCI and 21 healthy individuals were recruited. Serum DAO levels and cognitive function, measured by the Alzheimer's disease assessment scale-cognitive subscale (ADAS-cog) and the Mini-Mental Status Examination (MMSE), were monitored every 6 months. We employed multiple regressions to examine the role of DAO concentration in cognitive decline in the 2-year period. Results From baseline to endpoint (24 months), serum DAO levels increased significantly and cognitive ability declined according to both cognitive tests in the MCI patients. Among the healthy individuals, DAO concentrations also increased and MMSE scores declined; however, ADAS-cog scores didn’t change significantly. Further, DAO levels at both months 12 and 18 were predictive of cognitive impairment at month 24 among the MCI patients. Conclusions To our knowledge, this is the first study to demonstrate that blood DAO levels increased with cognitive deterioration among the MCI patients in a prospective manner. If replicated by future studies, blood DAO concentration may be regarded as a biomarker for monitoring cognitive change in the patients with MCI.

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“…Serine, specifically D-serine, is thought to be a critical excitatory neurotransmitter acting as a co-agonist of the N-methyl Daspartate (NMDA) receptor on neurons, and depletion due to deficient synthesis or racemase activity likely leads to catastrophic neurotoxicity [96]. Abnormal D-serine levels in the brain are thought to contribute to neurodegenerative disorders such as Alzheimer's disease and schizophrenia [97][98][99][100]. Expression of serine biosynthesis enzymes are highly regulated by several factors, including NRF2-ATF4 [101,102], c-Myc [103], and hypoxia inducible factors [104].…”

Section: Serine Glycine and Alaninementioning

confidence: 99%

Transporters at the Interface between Cytosolic and Mitochondrial Amino Acid Metabolism

2021

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Mitochondria are central organelles that coordinate a vast array of metabolic and biologic functions important for cellular health. Amino acids are intricately linked to the bioenergetic, biosynthetic, and homeostatic function of the mitochondrion and require specific transporters to facilitate their import, export, and exchange across the inner mitochondrial membrane. Here we review key cellular metabolic outputs of eukaryotic mitochondrial amino acid metabolism and discuss both known and unknown transporters involved. Furthermore, we discuss how utilization of compartmentalized amino acid metabolism functions in disease and physiological contexts. We examine how improved methods to study mitochondrial metabolism, define organelle metabolite composition, and visualize cellular gradients allow for a more comprehensive understanding of how transporters facilitate compartmentalized metabolism.

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D-serine Ameliorates Motor and Cognitive Impairments in β-amyloid 1-42 Injected Mice by Inhibiting JNK Signaling Pathway

Cited by 14 publications

References 51 publications

Visuo‐spatial learning and memory impairments in the 5xFAD mouse model of Alzheimer's disease: Effects of age, sex, albinism, and motor impairments

Visuo‐spatial learning and memory impairments in the 5xFAD mouse model of Alzheimer's disease: Effects of age, sex, albinism, and motor impairments

Blood D-Amino Acid Oxidase Levels Increased With Cognitive Decline Among People With Mild Cognitive Impairment: A Two-Year Prospective Study

Transporters at the Interface between Cytosolic and Mitochondrial Amino Acid Metabolism

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