Intraparenchymal NGF Infusions Rescue Degenerating Cholinergic Neurons

2000 ◽  
Vol 9 (5) ◽  
pp. 629-636 ◽  
Author(s):  
Mark H. Tuszynski
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Basal Forebrain ◽  
Neuronal Degeneration ◽  
Cholinergic Neurons ◽  
Dependent Manner ◽  
Axonal Sprouting ◽  
Adult Rats ◽  
Basal Forebrain Cholinergic Neurons ◽  
Age Related

Nerve growth factor (NGF) exerts both trophic (cell survival) and tropic (axonal growth-promoting) effects on several neuronal populations. In particular, its robust ability to prevent lesion-induced and spontaneous age-related basal forebrain cholinergic neuronal degeneration, and to promote mnemonic recovery, has suggested its potential use as a therapeutic agent in Alzheimer's disease. When infused intracerebroventricularly, however, NGF is associated with several adverse effects that make this delivery route impractical. The present study examined whether intraparenchymal infusions of NGF adjacent to cholinergic neuronal soma are an effective and well-tolerated means of providing NGF to degenerating cholinergic neurons. Cholinergic neuronal rescue together with axonal sprouting responses and local tissue damage in the brain were assessed in adult rats that underwent complete unilateral fornix transections, followed by intraparenchymal infusions of recombinant human NGF for a 2-week period. Intraparenchymal NGF infusions prevented the degeneration of 94.7 ± 6.6% of basal forebrain cholinergic neurons compared to 21.7 ± 2.6% in vehicle-infused animals (p < 0.0001). Cholinergic axons sprouted toward the intraparenchymal NGF source in an apparent gradient-dependent manner. Glial responses to intraparenchymal infusions were minimal, and no apparent toxic effects of the infusions were observed. Thus, when infused intraparenchymally, NGF rescues basal forebrain cholinergic neurons, alters the topography of axonal sprouting responses, and does not induce adverse affects over a 2-week infusion period. Intraparenchymal NGF delivery merits further study at longer term time points as a means of treating the cholinergic component of neuronal loss in Alzheimer's disease.

scholarly journals Basal Forebrain Cholinergic Neurons: Linking Down Syndrome and Alzheimer’s Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Jose L. Martinez ◽  
Matthew D. Zammit ◽  
Nicole R. West ◽  
Bradley T. Christian ◽  
Anita Bhattacharyya
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Down Syndrome ◽  
Basal Forebrain ◽  
Critical Role ◽  
Memory Loss ◽  
Cholinergic Neurons ◽  
Cholinergic Innervation ◽  
Attention And Memory ◽  
Basal Forebrain Cholinergic Neurons

Down syndrome (DS, trisomy 21) is characterized by intellectual impairment at birth and Alzheimer’s disease (AD) pathology in middle age. As individuals with DS age, their cognitive functions decline as they develop AD pathology. The susceptibility to degeneration of a subset of neurons, known as basal forebrain cholinergic neurons (BFCNs), in DS and AD is a critical link between cognitive impairment and neurodegeneration in both disorders. BFCNs are the primary source of cholinergic innervation to the cerebral cortex and hippocampus, as well as the amygdala. They play a critical role in the processing of information related to cognitive function and are directly engaged in regulating circuits of attention and memory throughout the lifespan. Given the importance of BFCNs in attention and memory, it is not surprising that these neurons contribute to dysfunctional neuronal circuitry in DS and are vulnerable in adults with DS and AD, where their degeneration leads to memory loss and disturbance in language. BFCNs are thus a relevant cell target for therapeutics for both DS and AD but, despite some success, efforts in this area have waned. There are gaps in our knowledge of BFCN vulnerability that preclude our ability to effectively design interventions. Here, we review the role of BFCN function and degeneration in AD and DS and identify under-studied aspects of BFCN biology. The current gaps in BFCN relevant imaging studies, therapeutics, and human models limit our insight into the mechanistic vulnerability of BFCNs in individuals with DS and AD.

scholarly journals The Promoted Generation of Basal Forebrain Cholinergic Neurons from Neural Progenitor Cells on Three-dimensional Graphene foam Scaffold

2021 ◽  
Author(s):  
Ziyun Jiang ◽  
Lingyan Yang ◽  
Linhong Zhou ◽  
Miao Xiao ◽  
Sancheng Ma ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Progenitor Cells ◽  
Basal Forebrain ◽  
Neural Progenitor Cells ◽  
Three Dimensional ◽  
Cholinergic Neurons ◽  
Neural Progenitor ◽  
Graphene Foam ◽  
Basal Forebrain Cholinergic Neurons

Abstract Background: An early substantial loss of basal forebrain cholinergic neurons (BFCNs) is a common property of Alzheimer’s disease and the generation of functional BFCNs is related to learning and memory deficits. As a biocompatible and conductive scaffold for growth of neural stem cells, three-dimensional graphene foam (3D-GF) supports applications in tissue engineering and regenerative medicine. Although its effects on differentiation have been demonstrated, the effect of 3D-GF scaffold on the generation of BFCNs still remains unknown. Methods: In this study, we used 3D-GF as a culture substrate for neural progenitor cells (NPCs) and demonstrated that this scaffold material promotes the differentiation of BFCNs while maintaining excellent cell viability and proliferation. Results: Immunofluorescence analysis, RT-PCR, western blotting and ELISA revealed that the efficiency of BFCN differentiation on 3D-GF was significantly greater than that on tissue culture polystyrene substrates. Furthermore, a cell adhesion study suggested that 3D-GF scaffold enhances the expression of adhesion proteins including vinculin, integrin and N-cadherin. These findings indicate that 3D-GF scaffold materials are excellent candidates for the differentiation of BFCNs from NPCs. Conclusion: These results suggest new opportunities for the application of 3D-GF scaffold as a neural scaffold for Alzheimer’s disease therapies based on NPCs. Trial registration: Not applicable.

Sign in / Sign up

Export Citation Format

Share Document