Effects of β-amyloid (1-42) Administration on the Main Neurogenic Niches of the Adult Brain: Amyloid-Induced Neurodegeneration Influences Neurogenesis

Abstract

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder and warrants further study as well as timely treatment. Additionally, the mechanisms of the brain’s intrinsic defense against chronic injury are not yet fully understood. Herein, we examined the response of the main neurogenic niches to amyloid exposure and the associated changes in structure and synaptic activity. Flow cytometry of Nestin-, Vimentin-, Nestin/Vimentin-, NeuN-, GFAP-, NeuN/GFAP-, NSE-, BrdU-, Wnt-, BrdU/Wnt-, VEGF-, Sox14-, VEGF/Sox14-, Sox10-, Sox2-, Sox10/Sox2-, Bax-, and Bcl-xL-positive cells was performed in the subventricular zone (SVZ), hippocampus, and cerebral cortex of rat brains on 90th day after intracerebroventricular (i.c.v.) single injection of a fraction of β-amyloid (Aβ) (1-42). The relative structural changes in these areas and disruptions to synaptic activity in the entorhinal cortex–hippocampus circuit were also evaluated. Our flow analyses revealed a reduction in the numbers of Nestin-, Vimentin-, and Nestin/Vimentin-positive cells in neurogenic niches and the olfactory bulb. These changes were accompanied by an increased number of BrdU-positive cells in the hippocampus and SVZ. The latter changes were strongly correlated with changes in the numbers of VEGF- and VEGF/Sox14-positive cells. The morphological changes were characterized by significant neural loss, a characteristic shift in entorhinal cortex–hippocampus circuit activity, and decreased spontaneous alternation in a behavioral test. We conclude that although an injection of Aβ (1-42) induced stem cell proliferation and triggered neurogenesis at a certain stage, this process was incomplete and led to neural stem cell immaturity. We propose the idea of enhancing adult neurogenesis as a promising strategy for preventing dementia at healthy elderly people andpeople at high risk for developing AD, or treating patients diagnosed with AD.

N-Acetylcysteine Amide against Aβ-Induced Alzheimer’s-like Pathology in Rats

“…This entire process is impeccably sensitive to OS, causing reduced neurogenesis [ 60 , 61 ]. The icv administration of Aβ1-42 peptide was previously shown to have adverse effects on adult neurogenesis [ 62 ]. Though our study did not evaluate the effect on the differentiation and migration of newly formed neurons, we observed a deteriorating effect on neuronal proliferation after Aβ1-42 peptide administration.…”

Brain Slice Derived Nerve Fibers Grow along Microcontact Prints and are Stimulated by Beta-Amyloid(42)

“…Soluble oligomeric Aβ at physiological levels promotes dendritic complexity in hippocampal neurons, indicating that dendritic stability and dynamics are modulated by Aβ [6]. However, although amyloid exposure initially stimulates neurogenesis, it fails to complete the maturation cascade [7]. Other studies suggest that Aβ peptide toxicity is associated with active fibrillization processes [54].…”

“…Positive regulation is observed solely within the physiological concentration range of Aβ, whereas abnormal high levels exert negative effects on synaptic function [4,5]. Soluble oligomeric Aβ at physiological levels promotes neuronal complexity indicating that their stability and dynamics are modulated by Aβ [6,7]. In contrast, non-soluble Aβ aggregates negatively affect the morphology of the neurites and cell viability [8].…”

c-Cbl Regulates Murine Subventricular Zone-Derived Neural Progenitor Cells in Dependence of the Epidermal Growth Factor Receptor

“…Adult neurogenesis in the murine SVZ plays an important role in brain function, including olfactory bulb (OB) neurogenesis, neurovascular coupling, and brain repair after injury [3,4]. An alteration in the number of TAPs in the SVZ is implicated in a range of neurological disorders, including Huntington's disease [5], Parkinson's disease [6], vascular dementia [7], glioblastoma multiforme [8], Alzheimer's disease [9,10], and cerebrovascular damage [11]. Thus, understanding the mechanisms that influence proliferation of NSCs in the SVZ is crucial for the development of therapeutic strategies for these diseases.…”