Reversal of spatial memory impairment by phosphodiesterase 3 inhibitor cilostazol is associated with reduced neuroinflammation and increased cerebral glucose uptake in aged male mice

Yanai, Shuichi; Tago, Tetsuro; Toyohara, Jun; Arasaki, Tomoko; Endo, Shogo

doi:10.3389/fphar.2022.1031637

Cited by 4 publications

(3 citation statements)

References 172 publications

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“…Our behavior data confirmed that aged mice are more likely to fail at an object placement task than their younger counterparts. This goes along with studies analyzing similar spatial memory tasks that have found deficits in aged animals (37,38). Our results also highlight the well-described heterogeneity present during normal aging, as about half of aged mice were still able to pass the test (39,40).…”

Section: Discussionsupporting

confidence: 87%

Delayed formation of neural representations of space in aged mice

McDermott

Frechou

Jordan

et al. 2023

Preprint

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Aging is associated with cognitive deficits, with spatial memory being very susceptible to decline. The hippocampal dentate gyrus (DG) is important for the processing of spatial information in the brain and is particularly vulnerable to aging, yet its sparse activity has led to difficulties in assessing changes in this area. Usingin vivotwo-photon calcium imaging, we compared DG neuronal activity and representations of space in young and aged mice walking on an unfamiliar treadmill. We found that calcium activity was significantly higher and less tuned to location in aged mice, resulting in decreased spatial information encoded in the DG. However, with repeated exposure to the same treadmill, both spatial tuning and information levels in aged mice became similar to young mice, while activity remained elevated. Our results show that spatial representations of novel environments are impaired in the aged hippocampus and gradually improve with increased familiarity. Moreover, while the aged DG is hyperexcitable, this does not disrupt neural representations of familiar environments.

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Section: Discussionsupporting

confidence: 87%

Delayed formation of neural representations of space in aged mice

McDermott

Frechou

Jordan

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Our behavior data confirmed that aged mice show a deficit in this task compared to their younger counterparts. This goes along with studies analyzing similar spatial memory tasks that have found deficits in aged animals (Wimmer et al, 2012;Yanai et al, 2022). Our results also highlight the welldescribed heterogeneity present during normal aging, as some of the aged mice were still able to perform well in this test (Hamieh et al, 2021).…”

Section: Discussionsupporting

confidence: 85%

Delayed formation of neural representations of space in aged mice

et al. 2023

View full text Add to dashboard Cite

Aging is associated with cognitive deficits, with spatial memory being very susceptible to decline. The hippocampal dentate gyrus (DG) is important for processing spatial information in the brain and is particularly vulnerable to aging, yet its sparse activity has led to difficulties in assessing changes in this area. Using in vivo two‐photon calcium imaging, we compared DG neuronal activity and representations of space in young and aged mice walking on an unfamiliar treadmill. We found that calcium activity was significantly higher and less tuned to location in aged mice, resulting in decreased spatial information encoded in the DG. However, with repeated exposure to the same treadmill, both spatial tuning and information levels in aged mice became similar to young mice, while activity remained elevated. Our results show that spatial representations of novel environments are impaired in the aged hippocampus and gradually improve with increased familiarity. Moreover, while the aged DG is hyperexcitable, this does not disrupt neural representations of familiar environments.

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“…The cognitive decline during aging is characterized by hippocampal dysfunction induced by neuronal loss and synaptic loss. These losses seem to be caused by the activation of immune cells, provoking neuroinflammation, mitochondria abnormalities, oxidative stress, decreased autophagy, and diminished Neurogenesis ( Echeverria, 2016 ; Echeverria et al, 2016a ; Yanai et al, 2022 ; Bathini et al, 2023 ; Chen et al, 2023 ; Choi and Tanzi, 2023 ; Dranovsky et al, 2023 ; Wang et al, 2023 ; Zhou et al, 2023 ). Thus, every year, the battle to preserve or augment cognitive abilities in the elderly becomes more critical for humanity.…”

Section: Introductionmentioning

confidence: 99%

Nicotinic acetylcholine receptors and learning and memory deficits in Neuroinflammatory diseases

2023

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Animal survival depends on cognitive abilities such as learning and memory to adapt to environmental changes. Memory functions require an enhanced activity and connectivity of a particular arrangement of engram neurons, supported by the concerted action of neurons, glia, and vascular cells. The deterioration of the cholinergic system is a common occurrence in neurological conditions exacerbated by aging such as traumatic brain injury (TBI), posttraumatic stress disorder (PTSD), Alzheimer’s disease (AD), and Parkinson’s disease (PD). Cotinine is a cholinergic modulator with neuroprotective, antidepressant, anti-inflammatory, antioxidant, and memory-enhancing effects. Current evidence suggests Cotinine’s beneficial effects on cognition results from the positive modulation of the α7-nicotinic acetylcholine receptors (nAChRs) and the inhibition of the toll-like receptors (TLRs). The α7nAChR affects brain functions by modulating the function of neurons, glia, endothelial, immune, and dendritic cells and regulates inhibitory and excitatory neurotransmission throughout the GABA interneurons. In addition, Cotinine acting on the α7 nAChRs and TLR reduces neuroinflammation by inhibiting the release of pro-inflammatory cytokines by the immune cells. Also, α7nAChRs stimulate signaling pathways supporting structural, biochemical, electrochemical, and cellular changes in the Central nervous system during the cognitive processes, including Neurogenesis. Here, the mechanisms of memory formation as well as potential mechanisms of action of Cotinine on memory preservation in aging and neurological diseases are discussed.

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Reversal of spatial memory impairment by phosphodiesterase 3 inhibitor cilostazol is associated with reduced neuroinflammation and increased cerebral glucose uptake in aged male mice

Cited by 4 publications

References 172 publications

Delayed formation of neural representations of space in aged mice

Delayed formation of neural representations of space in aged mice

Delayed formation of neural representations of space in aged mice

Nicotinic acetylcholine receptors and learning and memory deficits in Neuroinflammatory diseases

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