The influence of long-term tacrolimus treatment on cognitive function remains to be elucidated. Using chronic tacrolimus neurotoxicity in mice, we evaluated the influence of tacrolimus on cognitive function, synaptic balance, its regulating protein (Klotho), and oxidative stress in the hippocampus. Compared to vehicle-treated mice, tacrolimus-treated mice showed significantly decreased hippocampal-dependent spatial learning and memory function. Furthermore, tacrolimus caused synaptic imbalance as demonstrated by decreased excitatory synapses and increased inhibitory synapses, and downregulated Klotho in a dose-dependent manner; its downregulation was localized to excitatory hippocampal synapses. Moreover, tacrolimus increased oxidative stress and was associated with the activation of the PI3K/AKT pathway in the hippocampus. The present results indicate that tacrolimus impairs cognitive function via synaptic imbalance, and that these processes are associated with Klotho downregulation at synapses through tacrolimus-induced oxidative stress in the hippocampus.
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Posted 10 Mar, 2021
Received 14 Mar, 2021
Invitations sent on 14 Mar, 2021
On 03 Mar, 2021
On 28 Feb, 2021
On 25 Feb, 2021
Posted 10 Mar, 2021
Received 14 Mar, 2021
Invitations sent on 14 Mar, 2021
On 03 Mar, 2021
On 28 Feb, 2021
On 25 Feb, 2021
The influence of long-term tacrolimus treatment on cognitive function remains to be elucidated. Using chronic tacrolimus neurotoxicity in mice, we evaluated the influence of tacrolimus on cognitive function, synaptic balance, its regulating protein (Klotho), and oxidative stress in the hippocampus. Compared to vehicle-treated mice, tacrolimus-treated mice showed significantly decreased hippocampal-dependent spatial learning and memory function. Furthermore, tacrolimus caused synaptic imbalance as demonstrated by decreased excitatory synapses and increased inhibitory synapses, and downregulated Klotho in a dose-dependent manner; its downregulation was localized to excitatory hippocampal synapses. Moreover, tacrolimus increased oxidative stress and was associated with the activation of the PI3K/AKT pathway in the hippocampus. The present results indicate that tacrolimus impairs cognitive function via synaptic imbalance, and that these processes are associated with Klotho downregulation at synapses through tacrolimus-induced oxidative stress in the hippocampus.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
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