6) and that DR6 expression was upregulated within dystrophic neurites in and around amyloid plaques in adult DownвЂ™s syndrome (DS) patients 19 and after hypoxia. 5 More importantly, recent research showed that Bcl-xL-induced impairment of neurite outgrowth was dependent on upregulation of DR6 (ref. Further study demonstrated that this process could be triggered by N-terminal ОІ-amyloid precursor protein (N-APP) generated by trophic factor deprivation-induced cleavage of APP by ОІ-site APP cleaving enzyme 1 (BACE1) because N-APP acts as a necessary and sufficient ligand for DR6. 5 reported that NGF deprivation could trigger the timely axonal pruning and neuron death mediated by caspase-6 and caspase-3 respectively, which was dependent on activated death receptor-6 (DR6, also known as TNFRSF21), an orphan tumor necrosis factor receptor superfamily member. It has been known that neurotrophic factors, including nerve growth factor (NGF), brain-derived neurotrophic factor, neurotrophin-3 (NT-3) and NT-4, regulate cell fate decisions, axon growth and dendrite pruning through the Trk family of tyrosine kinase receptors and p75NTR. 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. 8, 9 Previous studies reported that impaired dendritic ramification was found in both Tg2576 mice and sporadic AD rats. The morphology of dendrites, one type of neurite, has a profound impact on neuronal information processing because the dendritic branching pattern determines the efficacy with which synaptic information is transmitted to the soma and dynamically integrates synaptic input. 4, 5, 6, 7 Importantly, impaired neurite outgrowth and A ОІ toxicity-induced abnormalities in synaptic function and axonal connectivity long precede somatic cell death in hippocampal neurons, 4 suggesting that inhibition of neurite degeneration would be a potential target to prevent or treat AD and VaD. 1, 2, 3 Neuronal cell death, a main cause of neuronal loss, can be triggered from either the cell body (soma) or the neurites, and the two processes are controlled by different molecular events. We conclude that miR-195 is involved in CBH-induced dendritic degeneration and neuron death through activation of the N-APP/DR6/caspase pathway.Д«rain atrophy induced by neuronal loss is a common hallmark of AlzheimerвЂ™s disease (AD) and vascular dementia (VaD), whose other hallmarks include A ОІ plaques, tau hyperphosphorylation and cholinergic neuron dysfunction. Overexpression of miR-195 using lenti-pre- miR-195 prevented these changes triggered by 2VO. 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. 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. It also led to increase in N-terminal ОІ -amyloid precursor protein (N-APP) and death receptor-6 (DR6) protein levels and in the activation of caspase-3 and caspase-6. 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. Impaired synaptic plasticity and neuron loss are hallmarks of AlzheimerвЂ™s disease and vascular dementia.

Image pro plus dendrite measure