What is the basal forebrain cholinergic system?
The basal forebrain cholinergic system is the population of neurons most affected by the neurodegenerative process
What hopes were raised in the last few years?
- In the last few years, hopes were raised that cell replacement therapy would provide cure by compensating the lost neuronal systems
What did Zhang et al. (2013) hypothesise?
- Zhang et al. (2013) hypothesized that transplantation of NSC into the hippocampal regions of APP1PS1 transgenic (Tg) mice, a well-established model of AD, would enhance the expression of synaptic proteins, which may be helpful for improving cognitive function
Zhang et al. (2013)'s results show what?
Their results showed that NSC transplantation signiﬁcantly improved spatial learning and memory function in Tg mice, a well-established model of AD, would enhance the expression of synaptic proteins, which may be helpful for improving cognitive function
The results obtained by real-time RT-PCR, immunofluorescence, and Western blot analyses demonstrated what?
The results obtained by real-time RT-PCR, immunoﬂuorescence, and Western blot analyses demonstrated that the expression of synaptophysin (SYN) and that of growth-associated protein-43 (GAP-43) in Tg-NSC mice, 8 weeks after transplantation, were signiﬁcantly improved compared with what was observed in Tg-Veh (control) mice. o This ﬁnding was conﬁrmed by the increase in the number of synapses in Tg-NSC mice as observed via electron microscopy
Zhang et al. (2013)'s results suggest what?
o Their results suggest that NSC-induced changes can recover memory loss in APP1PS1 transgenic mice, possibly by establishing new neural circuits resulting from the engrafted NSC
Previous studies show what?
Previous studies have shown the preservation of host neurons and recovery of function through the transplantation of human NSCs ex- pressing diverse functional genes, especially growth factors, in animal models of PD, ALS, stroke and spinal cord injury
Why have humans NSCs emerged as highly-effctive source of cells for genetics manipulation and gene transfer into the CNS ex vivo
Due to their high survival rate and ability to differentiate into both neurons and glial cells following transplantation into damaged tissue
What is the next crucial step of clnical application?
Finding an unlimited source of transplantable cells would be a welcome advance in cell therapy. In this regard, stem cell's infinite ability to self-renew and differentiate into neurons makes the search for cell therapy crucial to the next step of clinical application
As a growth factor secretory cell, human what have been investigated as graft source for PD?
- As a growth factor secretory cell, human HB1.F3 NSCs have been investigated as graft source for PD
Yasuhara et al. (2006) found transplantation of HB1.F3 cells into the striatum of rats with dopamine-depleted nigrostriatal pathway did what?
Transplantation of HB1.F3 cells into the striatum of rats with dopamine-depleted nigrostriatal pathway produced by the neurotoxin 6-OHDA significantly ameliorated parkinsonian behavioural symptoms compared with controls via neurotrophic factor secretion among other neurorestorative processes
Park et al. (2012) extended the use of HB1.F3 cells to AD by over-expressing what?
Park et al., 2012 extended the use of HB1.F3 cells to AD by over-expressing human choline acetyltransferase (ChAT) gene in this NSC line
Usign what, Park et al. (2012) achieved widespread chilinergic neuronal loss accompanied by memory deficits resembling many of the salient features of AD?
Using a neurotoxin rat AD model in which ethylcholine mustard aziridinium ion (AF64A) was intracerebroventricularly into the animal's brain, widespread cholinergic neuronal loss was detected and accompanied by memory deficits, resembling many of the salient features of AD
Transplantation of HB1.F3.ChAT NSCs into AF64A-lesioned rats led to what?
In contrast, transplantation of HB1.F3.ChAT NSCs into the AF64A-lesioned rats led to recovery of the learning and memory function, and induced elevated levels of acetylcholine (ACh) in cerebrospinal fluid (CSF)
Upon further investigation , the migration of transplanted F3.ChaT human NSCs was traced to what?
Upon further investigation, the migration of the transplanted F3.ChAT human NSCs was traced to various regions of the brain including the cerebral cortex, hippocampus, striatum and septum; these cells were seen to differentiate into neurons and astrocytes
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