Cognitive and behavioral evaluation of nutritional interventions in rodent models of brain aging and dementia

Wahl, Devin; Coogan, Sean C. P.; Solon-Biet, Samantha M.; Cabo, Rafael de; Haran, James B.; Raubenheimer, David; Cogger, Victoria C.; Mattson, Mark P.; Simpson, Stephen J.; Couteur, David G. Le

doi:10.2147/cia.s145247

Cited by 89 publications

(53 citation statements)

References 105 publications

(98 reference statements)

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“…After 6 weeks, we carried out a Y‐maze behavioral test to assess spatial working memory affected by Spns2KO. Alternation of arm entries in a Y‐maze is driven by an instinct to visit a novel place and requires the mouse to remember which arms it entered in its immediately previous exploration (for review, see Wahl et al, ). During the 3‐min test session in the Y‐maze, Aβ42‐treatment significantly reduced the probability of spontaneous alternation performance (SAP) to 51% (Con_Aβ) from 74% in vehicle‐treated control mice (Con) (Figure a).…”

Section: Resultsmentioning

confidence: 99%

Lipid transporter Spns2 promotes microglia pro‐inflammatory activation in response to amyloid‐beta peptide

Zhong

Jiang

Zhu

et al. 2018

Glia

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Accumulating evidence indicates that neuroinflammation contributes to the pathogenesis and exacerbation of neurodegenerative disorders, such as Alzheimer's disease (AD). Sphingosine‐1‐phosphate (S1P) is a pleiotropic bioactive lipid that regulates many pathophysiological processes including inflammation. We present evidence here that the spinster homolog 2 (Spns2), a S1P transporter, promotes microglia pro‐inflammatory activation in vitro and in vivo. Spns2 knockout (Spns2KO) in primary cultured microglia resulted in significantly reduced levels of pro‐inflammatory cytokines induced by lipopolysaccharide (LPS) and amyloid‐beta peptide 1–42 oligomers (Aβ42) when compared with littermate controls. Fingolimod (FTY720), a S1P receptor 1 (S1PR1) functional antagonist and FDA approved drug for relapsing–remitting multiple sclerosis, partially blunted Aβ42‐induced pro‐inflammatory cytokine generation, suggesting that Spns2 promotes microglia pro‐inflammatory activation through S1P‐signaling. Spns2KO significantly reduced Aβ42‐induced nuclear factor kappa B (NFκB) activity. S1P increased, while FTY720 dampened, Aβ42‐induced NFκB activity, suggesting that Spns2 activates microglia inflammation through, at least partially, NFκB pathway. Spns2KO mouse brains showed significantly reduced Aβ42‐induced microglia activation/accumulation and reduced levels of pro‐inflammatory cytokines when compared with age‐matched controls. More interestingly, Spns2KO ameliorated Aβ42‐induced working memory deficit detected by Y‐Maze. In summary, these results suggest that Spns2 promotes pro‐inflammatory polarization of microglia and may play a crucial role in AD pathogenesis.

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Section: Resultsmentioning

confidence: 99%

Lipid transporter Spns2 promotes microglia pro‐inflammatory activation in response to amyloid‐beta peptide

Zhong

Jiang

Zhu

et al. 2018

Glia

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“…Similarly, calorie restriction has been reported to reduce significantly hippocampal Aβ burden and expression of components of the γ‐secretase complex in female mice of the Tg2576 experimental model of cerebral amyloidosis (Schafer et al, ). Finally, many dietary interventions have been shown to ameliorate various cognitive and behavioral tests in rat models of aging and neurodegeneration (Wahl et al, ). Accordingly, clinical trials have been performed or are currently ongoing to evaluate the efficacy of such regimens on humans (Horie et al, ; Tussing‐Humphreys et al, ).…”

Section: How To Face the Cognitive Deterioration Of Ds Persons?mentioning

confidence: 99%

Accelerated bio‐cognitive aging in Down syndrome: State of the art and possible deceleration strategies

et al. 2019

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Down syndrome (DS) has been proposed by George Martin as a segmental progeroid syndrome since 1978. In fact, DS persons suffer from several age‐associated disorders much earlier than euploid persons. Furthermore, a series of recent studies have found that DS persons display elevated levels of age biomarkers, thus supporting the notion that DS is a progeroid trait. Nowadays, due to the progressive advancements in social inclusion processes and medical assistance, DS persons live much longer than in the past; therefore, the early‐onset health problems of these persons are becoming an urgent and largely unmet social and medical burden. In particular, the most important ailment of DS persons is the accelerated cognitive decline that starts when they reach about 40 years of age. This decline can be at least in part counteracted by multi‐systemic approaches including early‐onset cognitive training, physical activity, and psychosocial assistance. However, no pharmacological treatment is approved to counteract this decline. According to the most advanced conceptualization of Geroscience, tackling the molecular mechanisms underpinning the aging process should be a smart/feasible strategy to combat and/or delay the great majority of age‐related diseases, including cognitive decline. We think that a debate is needed urgently on if (and how) this strategy could be integrated in protocols to face DS‐associated dementia and overall unhealthy aging. In particular we propose that, on the basis of data obtained in different clinical settings, metformin is a promising candidate that could be exploited to counteract cognitive decline in DS.

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“…The brain is particularly susceptible to deterioration and neurodegeneration; the progressive loss of structure or function of neurones, can be found to varying degrees in the brains of all age groups (Wyss-Coray, 2016). Such changes are irreversible, non-curative, contribute to agerelated declines in cognitive function and memory and are a major risk factor for neurological disorders, including Parkinson's and Alzheimer's disease (Wahl et al, 2017;Wyss-Coray, 2016). As the age of the population increases, so does the socio-economic burden of neurodegeneration thus highlighting the need to identify neuroprotective agents (Gillette-Guyonnet et al, 2013;Lalkovičová and Danielisová, 2016;Wahl et al, 2017;Wyss-Coray, 2016).…”

Section: Introductionmentioning

confidence: 99%

In vitro neuroprotective activities of two distinct probiotic consortia

Michael

Davies

Loxley

et al. 2019

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Neurodegeneration has been linked to changes in the gut microbiota and this study compares the neuroprotective capability of two bacterial consortia, known as Lab4 and Lab4b, using the established SH-SY5Y neuronal cell model. Firstly, varying total antioxidant capacities (TAC) were identified in the intact cells from each consortia and their secreted metabolites, referred to as conditioned media (CM). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Crystal Violet (CV) assays of cell viability revealed that Lab4 CM and Lab4b CM could induce similar levels of proliferation in SH-SY5Y cells and, despite divergent TAC, possessed a comparable ability to protect undifferentiated and retinoic acid-differentiated cells from the cytotoxic actions of rotenone and undifferentiated cells from the cytotoxic actions of 1-methyl-4-phenylpyridinium iodide (MPP+). Lab4 CM and Lab4b CM also had the ability to attenuate rotenone-induced apoptosis and necrosis with Lab4b inducing the greater effect. Both consortia showed an analogous ability to attenuate intracellular reactive oxygen species accumulation in SH-SY5Y cells although the differential upregulation of genes encoding glutathione reductase and superoxide dismutase by Lab4 CM and Lab4b CM, respectively, implicates the involvement of consortia-specific antioxidative mechanisms of action. This study implicates Lab4 and Lab4b as potential neuroprotective agents and justifies their inclusion in further in vivo studies.

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Cognitive and behavioral evaluation of nutritional interventions in rodent models of brain aging and dementia

Cited by 89 publications

References 105 publications

Lipid transporter Spns2 promotes microglia pro‐inflammatory activation in response to amyloid‐beta peptide

Lipid transporter Spns2 promotes microglia pro‐inflammatory activation in response to amyloid‐beta peptide

Accelerated bio‐cognitive aging in Down syndrome: State of the art and possible deceleration strategies

In vitro neuroprotective activities of two distinct probiotic consortia

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