Astrocyte Regulation of Synaptic Plasticity and Repair in the Aging Brain

2013 new Scholar Award in aging

The aging brain has a decreased ability to lay down new memories, and this decrease is exacerbated in diseases of aging such as stroke and Alzheimer’s disease. This cognitive decline is not only due to the death of neurons, but also during aging there is a loss of neuronal connections called synapses, as well as a decline in function of the remaining synapses. We are investigating the role that non-neuronal cells play in stabilizing synaptic connections and function in the aging brain, with a focus on a class of glial cells called astrocytes. Astrocytes make up half of the cells in the human brain and are closely associated with neuronal synapses, and studies in the developing brain have shown that astrocytes are essential for neurons to form synaptic connections with each other. Astrocytes can regulate neuronal synapses by secreting factors that affect both synapse formation and synaptic function. Based on the strong evidence of a role for astrocytes in developmental synapse formation and function, we will test the following hypothesis: synaptic function and stability in the aging brain is impaired due to a decrease in astrocytic production of permissive synaptogenic factors and an increase in astrocytic production of factors that destabilize synapses. To examine this hypothesis we will identify the molecular changes to astrocytes during the aging process and then determine how these changes in aging affect the synaptic connections between neurons. We will examine whether astrocytes play a role in loss of synaptic function as well as identifying the astrocyte-derived molecules that may regulate this process. The identification of novel astrocyte-secreted factors that regulate synapses will provide new targets for repairing synaptic circuitry during aging and disorders of aging such as stroke and Alzheimer’s disease.

Nicola Allen Ph.D.
Salk Institute for Biological Studies