Age-related cognitive decline in spatial learning and memory of C57BL/6J mice

Hendrickx, Jhana O.; Moudt, Sofie De; Calus, Elke; Deyn, Peter Paul De; Dam, Debby Van; Meyer, Guido

doi:10.1016/j.bbr.2021.113649

Cited by 26 publications

(18 citation statements)

References 21 publications

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“…The authors concluded that 4–6 month old C57BL/6 mice exhibited reduced locomotor activity toward novel environments, depression-related behavior, and deficits in spatial and cued fear memory, amongst others, compared to 2–3 month old C57BL/6 mice [ 43 ]. These results align with our recent findings, which demonstrated an age-related cognitive decline in spatial learning and memory in C57BL/6J mice from the age of 6 months onward [ 44 ]. In addition to this report, our results showed a significant effect of L-NAME treatment on spatial learning and memory in adult (6 month old) male C57BL/6 mice.…”

Section: Discussionsupporting

confidence: 93%

Long-Term Pharmacological Inhibition of the Activity of All NOS Isoforms Rather Than Genetic Knock-Out of Endothelial NOS Leads to Impaired Spatial Learning and Memory in C57BL/6 Mice

et al. 2021

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Increasing epidemiological and experimental evidence points to a link between arterial stiffness and rapid cognitive decline. However, the underlying mechanism linking the two diseases is still unknown. The importance of nitric oxide synthases in both diseases is well-defined. In this study, we introduced arterial stiffness in both genetic (eNOS−/−, endothelial nitric oxide synthase knockout) and pharmacological (N(G)-nitro-L-arginine methyl ester (L-NAME) treatment) NO dysfunction models to study their association with cognitive decline. Our findings demonstrate that the non-selective inhibition of NOS activity with L-NAME induces cardiac dysfunction, arterial stiffness, and a decline in hippocampal-dependent learning and memory. This outcome demonstrates the importance of neuronal NOS (nNOS) in both cardiovascular and neurological pathophysiology and its potential contribution in the convergence between arterial stiffness and cognitive decline.

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Section: Discussionsupporting

confidence: 93%

Long-Term Pharmacological Inhibition of the Activity of All NOS Isoforms Rather Than Genetic Knock-Out of Endothelial NOS Leads to Impaired Spatial Learning and Memory in C57BL/6 Mice

et al. 2021

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“…In aging mice of 22M, a decreased exploration and spatial memory ability were observed using open field test and Morris water maze, which were consistent with previous studies ( 20 , 21 ). As we know, exploration and spatial memory ability assessed by open field test and Morris water maze respectively are hippocampus-dependent type of exploration and memory ability ( 22 , 23 ).…”

Section: Discussionsupporting

confidence: 92%

Myristic acid alleviates hippocampal aging correlated with GABAergic signaling

et al. 2022

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Previous studies have shown that myristic acid (MA), a saturated fatty acid, could promote the proliferation and differentiation of neural stem cells in vitro. However, the effect of MA on hippocampal neurons aging has not been reported in vivo. Here we employed 22-month-old naturally aged C57BL/6 mice to evaluate the effect and mechanism of MA on hippocampal aging. First, we examined a decreased exploration and spatial memory ability in aging mice using the open field test and Morris water maze. Consistently, aging mice showed degenerative hippocampal histomorphology by H&E and Nissl staining. In terms of mechanism, imbalance of GABRB2 and GABRA2 expression in aging mice might be involved in hippocampus aging by mRNA high throughput sequencing (mRNA-seq) and immunohistochemistry (IHC) validation. Then, we revealed that MA alleviated the damage of exploration and spatial memory ability and ameliorated degeneration and aging of hippocampal neurons. Meanwhile, MA downregulated GABRB2 and upregulated GABRA2 expression, indicating MA might alleviate hippocampal aging correlated with GABAergic signaling. In conclusion, our findings revealed MA alleviated hippocampal aging correlated with GABAergic signaling, which might provide insight into the treatment of aging-associated diseases.

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“…Interestingly, for most behaviors, 8–12-month-old mice exhibited more pronounced changes than the other age groups compared to the youngest group [ 21 ]. A more recent and similar study also reported age-related changes in spatial learning and memory in C57BL/6J mice [ 22 ]. However, this study tested the learning and memory functions at 2, 4, 6, 9 and 12 months of age and reported a gradual decline in these performances only from 6 months of age [ 22 ].…”

Section: Discussionmentioning

confidence: 69%

“…A more recent and similar study also reported age-related changes in spatial learning and memory in C57BL/6J mice [ 22 ]. However, this study tested the learning and memory functions at 2, 4, 6, 9 and 12 months of age and reported a gradual decline in these performances only from 6 months of age [ 22 ]. In another study, deficits were observed in the Hip-dependent contextual fear conditioning task in middle-aged mice.…”

Section: Discussionmentioning

confidence: 69%

Dynamic Changes in the Endocannabinoid System during the Aging Process: Focus on the Middle-Age Crisis

Nidadavolu

Bilkei-Gorzó

Effah

et al. 2022

IJMS

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Endocannabinoid (eCB) signaling is markedly decreased in the hippocampus (Hip) of aged mice, and the genetic deletion of the cannabinoid receptor type 1 (CB1) leads to an early onset of cognitive decline and age-related histological changes in the brain. Thus, it is hypothesized that cognitive aging is modulated by eCB signaling through CB1. In the present study, we detailed the changes in the eCB system during the aging process using different complementary techniques in mouse brains of five different age groups, ranging from adolescence to old age. Our findings indicate that the eCB system is most strongly affected in middle-aged mice (between 9 and 12 months of age) in a brain region-specific manner. We show that 2-arachidonoylglycerol (2-AG) was prominently decreased in the Hip and moderately in caudate putamen (CPu), whereas anandamide (AEA) was decreased in both Cpu and medial prefrontal cortex along with cingulate cortex (mPFC+Cg), starting from 6 months until 12 months. Consistent with the changes in 2-AG, the 2-AG synthesizing enzyme diacylglycerol lipase α (DAGLα) was also prominently decreased across the sub-regions of the Hip. Interestingly, we found a transient increase in CB1 immunoreactivity across the sub-regions of the Hip at 9 months, a plausible compensation for reduced 2-AG, which ultimately decreased strongly at 12 months. Furthermore, quantitative autoradiography of CB1 revealed that [3H]CP55940 binding markedly increased in the Hip at 9 months. However, unlike the protein levels, CB1 binding density did not drop strongly at 12 months and at old age. Furthermore, [3H]CP55940 binding was significantly increased in the lateral entorhinal cortex (LEnt), starting from the middle age until the old age. Altogether, our findings clearly indicate a middle-age crisis in the eCB system, which could be a potential time window for therapeutic interventions to abrogate the course of cognitive aging.

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Age-related cognitive decline in spatial learning and memory of C57BL/6J mice

Cited by 26 publications

References 21 publications

Long-Term Pharmacological Inhibition of the Activity of All NOS Isoforms Rather Than Genetic Knock-Out of Endothelial NOS Leads to Impaired Spatial Learning and Memory in C57BL/6 Mice

Long-Term Pharmacological Inhibition of the Activity of All NOS Isoforms Rather Than Genetic Knock-Out of Endothelial NOS Leads to Impaired Spatial Learning and Memory in C57BL/6 Mice

Myristic acid alleviates hippocampal aging correlated with GABAergic signaling

Dynamic Changes in the Endocannabinoid System during the Aging Process: Focus on the Middle-Age Crisis

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