Astroglia-Derived BDNF and MSK-1 Mediate Experience- and Diet-Dependent Synaptic Plasticity

Area of Science:

• Neuroscience
• Cell Biology
• Aging Research

Background:

• Synaptic plasticity, vital for learning and memory, is influenced by lifestyle factors like diet and activity.
• Brain-derived neurotrophic factor (BDNF) and MSK1 kinase are implicated in synaptic scaling.
• Astroglia's role in releasing BDNF via calcium-dependent pathways is a recent discovery.

Purpose of the Study:

• To investigate the role of astroglia-derived BDNF in homeostatic synaptic plasticity within the aging brain.
• To examine how experience and diet affect synaptic transmission and plasticity in mice with impaired BDNF/MSK1 or glial exocytosis pathways.

Main Methods:

• Utilized transgenic mice models: MSK1 kinase dead knock-in (MSK1 KD) and dnSNARE mice, which have impaired BDNF/MSK1 and glial exocytosis, respectively.
• Assessed synaptic transmission and plasticity under conditions of prolonged astrocyte activation, environmental enrichment (EE), and caloric restriction (CR).
• Measured calcium signaling in cortical astrocytes and quantified excitatory and inhibitory synaptic currents.

Main Results:

• Prolonged astrocyte activation led to BDNF-dependent increases in excitatory synapse efficacy and synaptic bouton size.
• EE and CR enhanced astrocyte calcium signaling and modulated synaptic currents in aged wild-type mice, counteracting aging effects.
• EE and CR benefits on synaptic transmission and plasticity were significantly diminished in MSK1 KD and dnSNARE mice.

Conclusions:

• Astroglial BDNF release is essential for the homeostatic regulation of cortical synapses.
• Environmental enrichment and caloric restriction promote synaptic plasticity and transmission in aging brains through astroglial BDNF signaling.
• Targeting astroglial pathways may offer therapeutic strategies for age-related cognitive decline.