Differential effect of age on the brain fatty acid levels and their correlation with animal cognitive status in mice

Yetimler, Berrak; Ulusoy, Kemal Gokhan; Çelik, Turgay; Jakubowska-Doğru, Ewa

doi:10.1016/j.pbb.2012.07.009

Cited by 14 publications

(16 citation statements)

References 60 publications

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“…We performed this median-split based on the theoretical notion that proximity can be used as an index of individual differences in spatial learning among aged animals (Gallagher et al, 1993). We also consulted a similar dichotomization procedure used in previous MWM studies in rodents that focused on separating older subjects into two performance groups with respect to proximity (i.e., separating older subjects who scored above and below the mean cumulative or average proximity value of the younger subjects by 2 to 3 SD s of the young’s mean, see Zamzow, Elias, Acosta, Escobedo, & Magnusson, 2016; Gallagher et al, 1993; Rowe et al, 2007; Yetimler, Ulusoy, Çelik, & Jakubowska-Doğru, 2012). In addition, we examined the distribution of the CCProx values of the older adults [skewness = 0.48 (“0” in a normal distribution); kurtosis = −0.57 (“3” in a normal distribution)].…”

Section: Resultsmentioning

confidence: 99%

The application of a rodent-based Morris water maze (MWM) protocol to an investigation of age-related differences in human spatial learning.

Zhong

Magnusson

Swarts

et al. 2017

Behavioral Neuroscience

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The current study applied a rodent-based Morris water maze (MWM) protocol to an investigation of search performance differences between young and older adult humans. To investigate whether similar age-related decline in search performance could be seen in humans based on the rodent-based protocol, we implemented a virtual MWM (vMWM) that has characteristics similar to those of the MWM used in previous studies of spatial learning in mice. Through the use of a proximity to platform measure, robust differences were found between healthy young and older adults in search performance. After dividing older adults into good and poor performers based on a median-split of their corrected cumulative proximity (CCProx) values, the age effects in place learning were found to be largely related to search performance differences between the young and poor-performing older adults. When compared to the young, poor-performing older adults exhibited significantly higher proximity values in 83% of 24 place trials and overall in the probe trials that assessed spatial learning in the absence of the hidden platform. In contrast, good-performing older adults exhibited patterns of search performance that were comparable to that of the younger adults in most place and probe trials. Taken together, our findings suggest that the low search accuracy in poor-performing older adults stemmed from potential differences in strategy selection, differences in assumptions or expectations of task demands, as well as possible underlying functional and/or structural changes in the brain regions involved in vMWM search performance.

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Section: Resultsmentioning

confidence: 99%

The application of a rodent-based Morris water maze (MWM) protocol to an investigation of age-related differences in human spatial learning.

Zhong

Magnusson

Swarts

et al. 2017

Behavioral Neuroscience

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“…Proximity measures were corrected for start position (Das et al 2012). Based on reference memory acquisition performance in the place trials, the old mice were divided into two categories for BReference memory-Good^(RG; N = 7) and BReference memory-Bad^(RB; N = 5) learners as previously described (Lee et al 1994;Rowe et al 2007;Yetimler et al 2012) with some modifications. The criteria for RB old learners were established by selecting old mice with average 2-day reference scores that were 2 standard deviations above the mean of the young mice, while RG old learners were within the same 2 standard deviation window (Fig.…”

Section: Discussionmentioning

confidence: 99%

Higher levels of phosphorylated Y1472 on GluN2B subunits in the frontal cortex of aged mice are associated with good spatial reference memory, but not cognitive flexibility

Zamzow¹,

Elias

Acosta

et al. 2016

AGE

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The N-methyl-D-aspartate receptor (NMDAr) is particularly vulnerable to aging. The GluN2B subunit of the NMDAr, compared to other NMDAr subunits, suffers the greatest losses of expression in the aging brain, especially in the frontal cortex. While expression levels of GluN2B mRNA and protein in the aged brain are well documented, there has been little investigation into agerelated posttranslational modifications of the subunit. In this study, we explored some of the mechanisms that may promote differences in the NMDAr complex in the frontal cortex of aged animals. Two ages of mice, 3 and 24 months, were behaviorally tested in the Morris water maze. The frontal cortex and hippocampus from each mouse were subjected to differential centrifugation followed by solubilization in Triton X-100. Proteins from Triton-insoluble membranes, Tritonsoluble membranes, and intracellular membranes/ cytosol were examined by Western blot. Higher levels of GluN2B tyrosine 1472 phosphorylation in frontal cortex synaptic fractions of old mice were associated with better reference learning but poorer cognitive flexibility. Levels of GluN2B phosphotyrosine 1336 remained steady, but there were greater levels of the calpain-induced 115 kDa GluN2B cleavage product on extrasynaptic membranes in these old good learners. There was an age-related increase in calpain activity, but it was not associated with better learning. These data highlight a unique aging change for aged mice with good spatial learning that might be detrimental to cognitive flexibility. This study also suggests that higher levels of truncated GluN2B on extrasynaptic membranes are not deleterious to spatial memory in aged mice.

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“…While aging-related decline in DHA levels was observed in various rodent brain regions (Lopez et al, 1995; Little et al, 2007; Barcelo-Coblijn et al, 2003; Favrelier et al, 2000), others found lack of such effects (Yetmler et al, 2012). Some human studies indicated that aging has no appreciable influence on DHA contents in cerebral cortex (Carver et al, 2001), frontal cortex, hippocampus and pons (Soderberg M, 1991).…”

Section: Discussionmentioning

confidence: 99%

Role of DHA in aging-related changes in mouse brain synaptic plasma membrane proteome

Sidhu¹,

Huang²,

Desai³

et al. 2016

Neurobiology of Aging

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Aging has been related to diminished cognitive function, which could be a result of ineffective synaptic function. We have previously shown that synaptic plasma membrane (SPM) proteins supporting synaptic integrity and neurotransmission were down-regulated in docosahexaenoic acid (DHA)-deprived brains, suggesting an important role of DHA in synaptic function. In this study, we demonstrate aging-induced synaptic proteome changes and DHA-dependent mitigation of such changes using mass spectrometry (MS)-based protein quantitation combined with western blot or mRNA analysis. We found significant reduction of 15 SPM proteins in aging brains including fodrin-α, synaptopodin, PSD-95, SV2B, SNAP25, SNAP-α, NR2B, AMPA2, AP2, VGluT1, munc18-1, dynamin-1, VAMP2, rab3A, and EAAT1, most of which are involved in synaptic transmission. Notably, the first nine proteins were further reduced when brain DHA was depleted by diet, indicating that DHA plays an important role in sustaining these synaptic proteins down-regulated during aging. Reduction of two of these proteins was reversed by raising the brain DHA level by supplementing aged animals with an omega-3 fatty acid sufficient diet for 2 months. The recognition memory compromised in DHA-depleted animals was also improved. Our results suggest a potential role of DHA in alleviating aging-associated cognitive decline by offsetting the loss of neurotransmission-regulating synaptic proteins involved in synaptic function.

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Differential effect of age on the brain fatty acid levels and their correlation with animal cognitive status in mice

Cited by 14 publications

References 60 publications

The application of a rodent-based Morris water maze (MWM) protocol to an investigation of age-related differences in human spatial learning.

The application of a rodent-based Morris water maze (MWM) protocol to an investigation of age-related differences in human spatial learning.

Higher levels of phosphorylated Y1472 on GluN2B subunits in the frontal cortex of aged mice are associated with good spatial reference memory, but not cognitive flexibility

Role of DHA in aging-related changes in mouse brain synaptic plasma membrane proteome

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