Synaptic development in the human fetus: a morphometric analysis of normal and Down's syndrome neocortex

Area of Science:

• Neuroscience
• Developmental Biology
• Genetics

Background:

• Synaptic development is crucial for proper brain function.
• Down syndrome is associated with altered brain development.
• Understanding synaptic maturation in Down syndrome is important for identifying potential therapeutic targets.

Purpose of the Study:

• To investigate synaptic development in the sensorimotor neocortex of normal and Down syndrome brains.
• To compare synaptic density and maturity across different developmental ages.
• To identify potential alterations in synaptic parameters in Down syndrome during development.

Main Methods:

• Postmortem brain tissue from normal and Down syndrome individuals (12-40 weeks postconception) was analyzed.
• Electron microscopy with osmium and EPTA staining was used to examine synaptic structures.
• Systematic photomicrograph analysis quantified synaptic density, maturity (mature/primitive, asymmetrical/symmetrical contacts), and membrane dimensions.

Main Results:

• Synaptic density increased with developmental age in both normal and Down syndrome tissues.
• Measures of synaptic maturity, such as the ratio of mature to primitive and asymmetrical to symmetrical contacts, also increased with age.
• In Down syndrome tissue, synaptic parameter development was less consistent, with reduced parameters observed in later developmental stages compared to normal tissue.

Conclusions:

• Synaptic development, including density and maturity, progresses throughout fetal development in the human neocortex.
• While synaptic development occurs in Down syndrome brains, it appears less consistent and potentially reduced in later stages compared to normal development.
• These findings highlight potential neurodevelopmental differences in Down syndrome that may impact brain circuitry and function.