CaMKII-dependent dendrite ramification and spine generation promote spatial training-induced memory improvement in a rat model of sporadic Alzheimer's disease

Jiang, Xia; Chai, Gaoshang; Wang, Zhi-Hao; Hu, Yu; Li, Xiaoguang; Ma, Zhiwei; Wang, Qun; Wang, Jian‐Zhi; Liu, Gongping

doi:10.1016/j.neurobiolaging.2014.10.018

Cited by 38 publications

(19 citation statements)

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“…23, 24, 25 We first observed the morphology of dendrites in the CA1 and dentate gyrus (DG) regions of the hippocampus and in the cortex by Golgi staining. 11 We found significant decreases in the total length and numbers of dendrites of pyramidal and granular neurons in the hippocampal CA1 (Figures 1a, e and i) and DG regions (Figures 1b, f and j) in 2VO rats compared with those of the sham control group. Interestingly, although the length and numbers of secondary and tertiary dendrites were reduced in both pyramidal and granular neurons in the hippocampal CA1 and DG regions of 2VO rats, those parameters were not changed in primary dendrites (Figures 1e, f, i and j).…”

Section: Resultsmentioning

confidence: 70%

“…4, 10, 11, 27 Our previous study reported that CBH from 2VO surgery could induce A β aggregation by upregulating both APP and BACE1 via low expression of miR-195 . 23 Hence, we speculated that miR-195 may affect the remodeling of dendrites.…”

Section: Discussionmentioning

confidence: 98%

“…4, 27, 28, 29 Recently, the dendritic branching pattern, which dynamically integrates synaptic input by transmitting electrical signals to the soma, 8, 9 was found to be remodeled, with impaired dendritic ramification, in both Tg2576 mice and sporadic AD rats. 10, 11 However, whether CBH can induce the remodeling of dendritic morphology is currently unclear. In the present study, we found that CBH by 2VO surgery induced significantly inhibited dendritic branching of the secondary and tertiary dendrites in all pyramidal and granular neurons in the hippocampus and cortex.…”

Section: Discussionmentioning

confidence: 99%

“…8, 9 Previous studies reported that impaired dendritic ramification was found in both Tg2576 mice and sporadic AD rats. 10, 11 Although chronic brain hypoperfusion (CBH), which is a preclinical condition of mild cognitive impairment (MCI) and may precede AD and VaD, 12, 13, 14 can produce neuron death, 15, 16, 17 whether CBH can induce dendritic morphological remodeling is currently unclear.…”

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confidence: 99%

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MicroRNA-195 prevents dendritic degeneration and neuron death in rats following chronic brain hypoperfusion

et al. 2017

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Impaired synaptic plasticity and neuron loss are hallmarks of Alzheimer’s disease and vascular dementia. Here, we found that chronic brain hypoperfusion (CBH) by bilateral common carotid artery occlusion (2VO) decreased the total length, numbers and crossings of dendrites and caused neuron death in rat hippocampi and cortices. It also led to increase in N-terminal β-amyloid precursor protein (N-APP) and death receptor-6 (DR6) protein levels and in the activation of caspase-3 and caspase-6. Further study showed that DR6 protein was downregulated by miR-195 overexpression, upregulated by miR-195 inhibition, and unchanged by binding-site mutation and miR-masks. Knockdown of endogenous miR-195 by lentiviral vector-mediated overexpression of its antisense molecule (lenti-pre-AMO-miR-195) decreased the total length, numbers and crossings of dendrites and neuron death, upregulated N-APP and DR6 levels, and elevated cleaved caspase-3 and caspase-6 levels. Overexpression of miR-195 using lenti-pre-miR-195 prevented these changes triggered by 2VO. We conclude that miR-195 is involved in CBH-induced dendritic degeneration and neuron death through activation of the N-APP/DR6/caspase pathway.

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Section: Resultsmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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MicroRNA-195 prevents dendritic degeneration and neuron death in rats following chronic brain hypoperfusion

et al. 2017

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“…CaMKII/IV is related with the complexity of neuronal dendritic spines 57, 58 . We observed that selective deletion of GSK-3β in DG excitatory neurons inhibited CaMKII activity with reduction of total and the phosphorylated CaMKIV.…”

Section: Discussionmentioning

confidence: 99%

GSK-3β deletion in dentate gyrus excitatory neuron impairs synaptic plasticity and memory

Liu

Xie

Zhou

et al. 2017

Sci Rep

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Increasing evidence suggests that glycogen synthase kinase-3β (GSK-3β) plays a crucial role in neurodegenerative/psychiatric disorders, while pan-neural knockout of GSK-3β also shows detrimental effects. Currently, the function of GSK-3β in specific type of neurons is elusive. Here, we infused AAV-CaMKII-Cre-2A-eGFP into GSK-3βlox/lox mice to selectively delete the kinase in excitatory neurons of hippocampal dentate gyrus (DG), and studied the effects on cognitive/psychiatric behaviors and the molecular mechanisms. We found that mice with GSK-3β deletion in DG excitatory neurons displayed spatial and fear memory defects with an anti-anxiety behavior. Further studies demonstrated that GSK-3β deletion in DG subset inhibited hippocampal synaptic transmission and reduced levels of GluN1, GluN2A and GluN2B (NMDAR subunits), GluA1 (AMPAR subunit), PSD93 and drebrin (postsynaptic structural proteins), and synaptophysin (presynaptic protein). GSK-3β deletion also suppressed the activity-dependent neural activation and calcium/calmodulin-dependent protein kinase II (CaMKII)/CaMKIV-cAMP response element binding protein (CREB) signaling. Our data suggest that GSK-3β in hippocampal DG excitatory neurons is essential for maintaining synaptic plasticity and memory.

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Modulation of Synaptic Plasticity by Exercise Training as a Basis for Ischemic Stroke Rehabilitation

Nie

Yang

2016

Cell Mol Neurobiol

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In recent years, rehabilitation of ischemic stroke draws more and more attention in the world, and has been linked to changes of synaptic plasticity. Exercise training improves motor function of ischemia as well as cognition which is associated with formation of learning and memory. The molecular basis of learning and memory might be synaptic plasticity. Research has therefore been conducted in an attempt to relate effects of exercise training to neuroprotection and neurogenesis adjacent to the ischemic injury brain. The present paper reviews the current literature addressing this question and discusses the possible mechanisms involved in modulation of synaptic plasticity by exercise training. This review shows the pathological process of synaptic dysfunction in ischemic roughly and then discusses the effects of exercise training on scaffold proteins and regulatory protein expression. The expression of scaffold proteins generally increased after training, but the effects on regulatory proteins were mixed. Moreover, the compositions of postsynaptic receptors were changed and the strength of synaptic transmission was enhanced after training. Finally, the recovery of cognition is critically associated with synaptic remodeling in an injured brain, and the remodeling occurs through a number of local regulations including mRNA translation, remodeling of cytoskeleton, and receptor trafficking into and out of the synapse. We do provide a comprehensive knowledge of synaptic plasticity enhancement obtained by exercise training in this review.

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CaMKII-dependent dendrite ramification and spine generation promote spatial training-induced memory improvement in a rat model of sporadic Alzheimer's disease

Cited by 38 publications

References 50 publications

MicroRNA-195 prevents dendritic degeneration and neuron death in rats following chronic brain hypoperfusion

MicroRNA-195 prevents dendritic degeneration and neuron death in rats following chronic brain hypoperfusion

GSK-3β deletion in dentate gyrus excitatory neuron impairs synaptic plasticity and memory

Modulation of Synaptic Plasticity by Exercise Training as a Basis for Ischemic Stroke Rehabilitation

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