Background Alzheimer’s Disease (AD) is a neurodegenerative disease and is the leading cause of dementia in late adult life. In 2015, 5.3 million Americans were diagnosed with AD, 5.1 million of whom were above the age of 65. AD is characterized by a progressive loss of cognitive function, and is associated with the accumulation of amyloid-B (AB) protein and hyperphosphorylated tau in the brain. Although the exact pathogenesis of AD is still uncertain, several hypotheses have been proposed to explain the mechanisms behind the cognitive deficits that are seen in AD. The amyloid cascade hypothesis, which asserts that amyloid precursor protein (APP) proteolysis results in the accumulation of AB peptides that aggregate to form extracellular plaques,
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Neural stem cells in the subgranular cell layer of the dentate gyrus, which are usually identified via BrdU staining, give rise to intermediate progenitors. These intermediate progenitors, in turn, create neuroblasts that express neuronal cell markers like DCX, which is a microtubule associated protein. These neuroblasts are hyperexcitable, and are known to activate and engage in long-term potentiation at lower thresholds for a given period of time compared to mature granule cells. Once these newborn neurons exit the cell cycle, they migrate to the inner granule cell layer and form axonal processes that project to the CA3, and dendritic processes that synapse in the molecular layer. These neurons start to exhibit the functional and morphological characteristics of mature neurons at 6 to 8 weeks of age, then undergo synaptic fine-tuning once they become integrated into the hippocampal circuitry and are maintained throughout life. This review aims to evaluate current research on structural and physiological alterations found in hippocampal neurogenesis of the rodent brain associated with Amyloid-beta plaque pathology and prodromal AD, as well as provide some insight on the behavioral manifestations that are observed rodents and …show more content…
Cells originating from the dentate gyrus normally take 2 weeks before neurites reach their target areas in the CA3 region of the hippocampus, and 4-7 weeks before they become integrated into the hippocampal network. Immature neurons are especially sensitive to the local environment during this critical period. To this end, Verret, et al. evaluated the survival rate for newborn hippocampal neurons in the dentate gyrus of 6-month old APP/PS1 mice. This double transgenic line is a widely-used mouse model used to study early-onset forms of AD. It expresses mutations in both the amyloid precursor (APP) and presenilin-1 (PS1) proteins, produces the AB protein at higher levels compared to its single transgenic counterparts (APP or PS1 mutants), and appears to have accelerated amyloid pathology. Verret, et al. observed a significant decrease in the number of proliferating cells examined 1 month after BrdU labeling, compared to nontransgenic or single mutation animals. More specifically, only 11.8% of the originally-labeled cells survived during the 30-day time frame, in contrast to the 20% survival rate in nontransgenic mice. Niidome et al. found similar results when they quantified BrdU-labeled cells in both the subgranular and subventricular
Neural stem cells in the subgranular cell layer of the dentate gyrus, which are usually identified via BrdU staining, give rise to intermediate progenitors. These intermediate progenitors, in turn, create neuroblasts that express neuronal cell markers like DCX, which is a microtubule associated protein. These neuroblasts are hyperexcitable, and are known to activate and engage in long-term potentiation at lower thresholds for a given period of time compared to mature granule cells. Once these newborn neurons exit the cell cycle, they migrate to the inner granule cell layer and form axonal processes that project to the CA3, and dendritic processes that synapse in the molecular layer. These neurons start to exhibit the functional and morphological characteristics of mature neurons at 6 to 8 weeks of age, then undergo synaptic fine-tuning once they become integrated into the hippocampal circuitry and are maintained throughout life. This review aims to evaluate current research on structural and physiological alterations found in hippocampal neurogenesis of the rodent brain associated with Amyloid-beta plaque pathology and prodromal AD, as well as provide some insight on the behavioral manifestations that are observed rodents and …show more content…
Cells originating from the dentate gyrus normally take 2 weeks before neurites reach their target areas in the CA3 region of the hippocampus, and 4-7 weeks before they become integrated into the hippocampal network. Immature neurons are especially sensitive to the local environment during this critical period. To this end, Verret, et al. evaluated the survival rate for newborn hippocampal neurons in the dentate gyrus of 6-month old APP/PS1 mice. This double transgenic line is a widely-used mouse model used to study early-onset forms of AD. It expresses mutations in both the amyloid precursor (APP) and presenilin-1 (PS1) proteins, produces the AB protein at higher levels compared to its single transgenic counterparts (APP or PS1 mutants), and appears to have accelerated amyloid pathology. Verret, et al. observed a significant decrease in the number of proliferating cells examined 1 month after BrdU labeling, compared to nontransgenic or single mutation animals. More specifically, only 11.8% of the originally-labeled cells survived during the 30-day time frame, in contrast to the 20% survival rate in nontransgenic mice. Niidome et al. found similar results when they quantified BrdU-labeled cells in both the subgranular and subventricular