Caleb Hernández

Introduction. Alzheimer’s Disease (AD) is a progressive neurogenerative disease influenced by a complex web of factors including genetics, age, lifestyle, and the environment¹. AD presents with progressive cognitive decline and memory loss¹. The age-related decline in hippocampal neurogenesis has been suggested to contribute to the cognitive deterioration common in AD patients². Pathological features of AD include amyloid beta plaques and neurofibrillary tangles³. Accumulation of these plaques and tangles lead to synaptic loss, mitochondrial dysfunction, and reduced levels of acetylcholine. Current treatments are only successful in managing the symptoms of AD. Current treatments include cholinesterase inhibitors and an NMDA antagonist¹. A current direction for potential treatment of AD revolves around the correlation between brain-derived neurotrophic factors (BDNF), exercise, and hippocampal neurogenesis. BDNF is a member of the neurotrophic family of growth factors³. BDNF acts on certain neurons in the CNS and PNS to promote survival of neurons and growth and differentiation of new neurons and synapses³. BDNF is very active in the hippocampus, cerebral cortex, and the basal forebrain³. These areas are vital for learning, memory, and higher thinking³. In the AD mouse model, exercise improved hippocampal neurogenesis, lowered amyloid-beta levels, increased the production of BDNF, and improved memory⁴. Methods. The 5xFAD mouse model was used to test the effects of BDNF, exercise, and hippocampal neurogenesis on the progression of AD. Adult hippocampal neurogenesis (AHN) was induced genetically and pharmaceutically using lentivirus expressing WNT3 protein and P7C3, respectively⁴. These mice were compared to a group that were exercised to promote AHN. Spatial pattern separation and reference and retention memory were measured using an eight-arm radial arm maze and Y-maze, respectively⁴. Results. BDNF promoted restoration of learning and memory deficits in the AD mouse model by mediating the restoration of dendritic spines and the recovery of synaptic markers synaptophysin and PSD-95⁵. Furthermore, lactate was shown to be a key metabolite in facilitating the beneficial effects of BDNF⁶. Inducing AHN alone did not produce a change in AD pathology nor memory improvement⁴. However, a combination of induced AHN and enhanced BDNF production improved memory in the mouse model⁴. Conclusion. BDNF and neurogenesis play an important role in hippocampal memory and learning. Exercise has been shown to improve hippocampal neurogenesis, lower amyloid-beta levels, increase BDNF production, and improve memory. AD patients, who are unable to exercise in their conditions, would benefit from treatment that mimics the benefits of exercise through BDNF.

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