Synaptic plasticity in Alzheimer’s disease and healthy aging

Abstract

The strength and efficiency of synaptic connections are affected by the environment or the experience of the individual. This property, called synaptic plasticity, is directly related to memory and learning processes and has been modeled at the cellular level. These types of cellular memory and learning models include specific stimulation protocols that generate a long-term strengthening of the synapses, called long-term potentiation, or a weakening of the said long-term synapses, called long-term depression. Although, for decades, researchers have believed that the main cause of the cognitive deficit that characterizes Alzheimer’s disease (AD) and aging was the loss of neurons, the hypothesis of an imbalance in the cellular and molecular mechanisms of synaptic plasticity underlying this deficit is currently widely accepted. An understanding of the molecular and cellular changes underlying the process of synaptic plasticity during the development of AD and aging will direct future studies to specific targets, resulting in the development of much more efficient and specific therapeutic strategies. In this review, we classify, discuss, and describe the main findings related to changes in the neurophysiological mechanisms of synaptic plasticity in excitatory synapses underlying AD and aging. In addition, we suggest possible mechanisms in which aging can become a high-risk factor for the development of AD and how its development could be prevented or slowed.

Environmental Enrichment Enhances Cav 2.1 Channel-Mediated Presynaptic Plasticity in Hypoxic–Ischemic Encephalopathy

“…Previous studies have demonstrated the close relationship between motor improvement, synaptic plasticity, and the altered expression of synaptic proteins [72][73][74]. Motor improvement is associated with the increase in the expression of presynaptic proteins [75,76].…”

Mitochondria-associated membranes (MAMs): a potential therapeutic target for treating Alzheimer’s disease

“…How might the perturbed intercellular Ca 2+ concentration mediated by MAMs bring about neurodegeneration and cognitive deficiency in AD? Based on our examination of the relevant studies we postulate this three mechanism: First, the increased release of Ca 2+ from the ER stores in presynaptic terminals can undermine synaptic plasticity through consuming the neurotransmitters or enhancing multiple postsynaptic responses such as long-term depression (LTD) and long-term potentiation (LTP) (Figure 3ii) [82], likely leading to a negative impact on the neuronal networks and memory function [83]. Second, the sustained high levels of intracellular Ca 2+ in neurons can indirectly contribute to neuronal degeneration in AD by promoting the Aβ deposition and NFTs formation (Figure 3iii).…”

In Pursuit of Healthy Aging: Effects of Nutrition on Brain Function

“…Together, all of the above age-induced cellular alterations culminate in neuronal dysfunction, and impaired functional (i.e., synaptic) and structural neuroplasticity (including adult hippocampal neurogenesis) [ 205 , 206 , 207 , 208 , 209 ]. Indeed, in the aged brain progenitor cells exhibit several features associated with mitochondrial dysregulation, including reduced mitochondrial oxidative metabolism [ 210 ], genetic alterations that affect the functioning of the mitochondrial ETC [ 211 ], and oxidative stress.…”