DiI-mediated analysis of presynaptic and postsynaptic structures in human postmortem brain tissue.

Area of Science:

• Neuroscience
• Synaptic Plasticity
• Aging Research

Background:

• Cognitive and psychiatric disorders are linked to synapse defects, but precise changes are unknown.
• Analyzing synaptic structures in human postmortem tissue is challenging due to limited methods.
• Microscale neuroanatomy changes can indicate synapse formation and function defects.

Purpose of the Study:

• To present an accurate, rapid, and inexpensive methodological pipeline for assessing human postmortem synaptic structures.
• To analyze presynaptic and postsynaptic structures in the human hippocampus across the lifespan.
• To validate the method's effectiveness on tissue with extended postmortem intervals.

Main Methods:

• Utilized small human postmortem brain tissue blocks.
• Employed immersion fixation and lipophilic dye (DiI) labeling.
• Performed analysis using confocal microscopy.

Main Results:

• Postsynaptic CA1 dendritic spine shape and density remain stable in adults.
• Presynaptic DG mossy fiber boutons exhibit significant structural rearrangements during normal aging.
• The method accurately quantifies CA1 spine densities even with postmortem intervals up to 28 hours.

Conclusions:

• The developed pipeline facilitates high-powered studies of human synaptic structures in health and disease.
• Mossy fiber synapses, crucial for learning and memory, demonstrate lifelong dynamism.
• This method overcomes limitations of shorter postmortem intervals, enabling broader research accessibility.