Cognitive Deficits and Disruption of Neurogenesis in a Mouse Model of Apolipoprotein E4 Domain Interaction

Adeosun, Samuel O.; Hou, Xu; Zheng, Baoying; Stockmeier, Craig A.; Ou, Xiao-Ming; Paul, Ian A.; Mosley, Thomas H.; Weisgraber, Karl H.; Wang, Jun Ming

doi:10.1074/jbc.m113.497909

Cited by 32 publications

(43 citation statements)

References 103 publications

(100 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Unfortunately, we did not evaluate mice cognition in the present study and therefore, we cannot confirm this speculationi.e. cognitive impairments in APOE4 mice [39,40]. Also, the activity of FATPs, FABPs and CPT1 remains to be further investigated since only the levels, and not activities, were measured in the present study.…”

Section: Discussionmentioning

confidence: 94%

Apolipoprotein E isoforms disrupt long-chain fatty acid distribution in the plasma, the liver and the adipose tissue of mice

Conway

Larouche

Alata

et al. 2014

Prostaglandins, Leukotrienes and Essential Fatty Acids

View full text Add to dashboard Cite

Evidences suggest that omega-3 fatty acid (n-3 PUFA) metabolism is imbalanced in apolipoprotein E epsilon 4 isoform carriers (APOE4). This study aimed to investigate APOE genotype-dependant modulation of FA profiles, protein and enzyme important to fatty acid (FA) metabolism in the adipose tissue, the liver and the plasma using human APOE-targeted replacement mouse-model (N=37). FA transport (FATP) and binding (FABP) protein levels in tissues and concentrations of liver carnitine palmitoyltransferase 1 (CPT1) were performed. N-3 PUFA concentration was >45% lower in the adipose tissue and liver of APOE4 mice compared to APOE3 mice. In APOE4 mice, there were higher levels of FATP and FABP in the liver and higher FATP in the adipose tissue compared to APOE2 mice. There was a trend towards higher CPT1 concentrations in APOE4 mice compared to APOE3 mice. Therefore, since APOE-isoform differences were not always in line with the unbalanced n-3 PUFA profiles in organs, other proteins may be involved in maintaining n-3 PUFA homeostasis in mice with different APOE-isoforms.

show abstract

Section: Discussionmentioning

confidence: 94%

Apolipoprotein E isoforms disrupt long-chain fatty acid distribution in the plasma, the liver and the adipose tissue of mice

Conway

Larouche

Alata

et al. 2014

Prostaglandins, Leukotrienes and Essential Fatty Acids

View full text Add to dashboard Cite

show abstract

“…Neurogenesis which has been shown to be involved in cognitive impairment and depression in humans and in a variety of rodent models, is a function of serotonergic regulation and may affect the response to antidepressants in both cognitive and affective behavioral domains (Adeosun et al, 2014;Alenina and Klempin, 2015;Anacker, 2014;Biscaro et al, 2012;Braun and Jessberger, 2014;Chadwick et al, 2011;Cho et al, 2015;Dimitrov et al, 2014;Gundersen et al, 2013;Hill et al, 2015;Jiang et al, 2015;Lin and Wang, 2014;Mendez-David et al, 2013;Morais et al, 2014;O'Leary and Cryan, 2014;Parihar et al, 2013;Pereira Dias et al, 2014;Ransome et al, 2012;Rotheneichner et al, 2014;Schoenfeld and Cameron, 2015;Seib et al, 2013;Serafini et al, 2014;Shetty, 2014;Suarez-Pereira et al, 2015;Yau et al, 2014). In young adult mice, antidepressants increase stem cell proliferation (Hodes et al, 2010;Santarelli et al, 2003;Tanti et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Reversal of age-associated cognitive deficits is accompanied by increased plasticity-related gene expression after chronic antidepressant administration in middle-aged mice

Abdourahman

Tamm

et al. 2015

Pharmacology Biochemistry and Behavior

View full text Add to dashboard Cite

Cognitive decline occurs during healthy aging, even in middle-aged subjects, via mechanisms that could include reduced stem cell proliferation, changed growth factor expression and/or reduced expression of synaptic plasticity genes. Although antidepressants alter these mechanisms in young rodents, their effects in older animals are unclear. In middle-aged mice, we examined the effects of a selective serotonin reuptake inhibitor (fluoxetine) and a multimodal antidepressant (vortioxetine) on cognitive and affective behaviors, brain stem cell proliferation, growth factor and gene expression. Twelve-month-old female C57BL/6 mice exhibited impaired visuospatial memory in the novel object placement (location) task associated with reduced expression of several plasticity-related genes. Chronic treatment with vortioxetine, but not fluoxetine, improved visuospatial memory and reduced depression-like behavior in the forced swim test in middle-aged mice. Vortioxetine, but not fluoxetine, increased hippocampal expression of several neuroplasticity-related genes in middle-aged mice (e.g., Nfkb1, Fos, Fmr1, Camk2a, Arc, Shank1, Nlgn2, and Rab3a). Neither drug reversed the age-associated decrease in stem cell proliferation. Hippocampal growth factor levels were not consistent with behavioral outcomes. Thus, a change in the expression of multiple genes involved in neuronal plasticity by antidepressant treatment was associated with improved cognitive function and a reduction in depression-like behavior in middle-aged mice.

show abstract

“…Neurogenesis appears to be increased in young animals and decreased with age, while apoptotic markers indicate enhanced cell death. Interestingly, these early cognitive and cellular changes take place in the absence of classical AD pathological hallmarks (Adeosun et al 2014). In another study, deletion of ApoE in mice results in reduced neurogenesis and knock-in of the human ApoE4 leads to impaired maturation of newborn neurons through a mechanism dependent on GABAergic signaling (Li et al 2009).…”

Section: Age-related Cognitive and Neurogenesis Decline In Animalsmentioning

confidence: 99%

Role of Adult Hippocampal Neurogenesis in Cognition in Physiology and Disease: Pharmacological Targets and Biomarkers

Costa

Lugert

Jagasia

2015

Cognitive Enhancement

View full text Add to dashboard Cite

Adult hippocampal neurogenesis is a remarkable form of brain structural plasticity by which new functional neurons are generated from adult neural stem cells/precursors. Although the precise role of this process remains elusive, adult hippocampal neurogenesis is important for learning and memory and it is affected in disease conditions associated with cognitive impairment, depression, and anxiety. Immature neurons in the adult brain exhibit an enhanced structural and synaptic plasticity during their maturation representing a unique population of neurons to mediate specific hippocampal function. Compelling preclinical evidence suggests that hippocampal neurogenesis is modulated by a broad range of physiological stimuli which are relevant in cognitive and emotional states. Moreover, multiple pharmacological interventions targeting cognition modulate adult hippocampal neurogenesis. In addition, recent genetic approaches have shown that promoting neurogenesis can positively modulate cognition associated with both physiology and disease. Thus the discovery of signaling pathways that enhance adult neurogenesis may lead to therapeutic strategies for improving memory loss due to aging or disease. This chapter endeavors to review the literature in the field, with particular focus on (1) the role of hippocampal neurogenesis in cognition in physiology and disease; (2) extrinsic and intrinsic signals that modulate hippocampal neurogenesis with a focus on pharmacological targets; and (3) efforts toward novel strategies pharmacologically targeting neurogenesis and identification of biomarkers of human neurogenesis.

show abstract

Cognitive Deficits and Disruption of Neurogenesis in a Mouse Model of Apolipoprotein E4 Domain Interaction

Cited by 32 publications

References 103 publications

Apolipoprotein E isoforms disrupt long-chain fatty acid distribution in the plasma, the liver and the adipose tissue of mice

Apolipoprotein E isoforms disrupt long-chain fatty acid distribution in the plasma, the liver and the adipose tissue of mice

Reversal of age-associated cognitive deficits is accompanied by increased plasticity-related gene expression after chronic antidepressant administration in middle-aged mice

Role of Adult Hippocampal Neurogenesis in Cognition in Physiology and Disease: Pharmacological Targets and Biomarkers

Contact Info

Product

Resources

About