Cell Neurochemistry

Cell neurochemistry encompasses the study of small molecules, ions and polymers that govern the function of neurons and glia. In living brain tissue, neurotransmitters such as glutamate, GABA and biogenic amines carry rapid signals, while peptides and lipid mediators modulate synaptic strength over longer timescales. Ionic gradients of sodium, potassium and calcium generate and propagate electrical activity, and their recovery is orchestrated by ion pumps and transporters. Beyond these classical actors, the extracellular matrix and perineuronal nets—complex assemblies of proteoglycans and glycosaminoglycans—provide structural support, regulate diffusion of neurochemicals and stabilise synapses. Astrocytes regulate neurochemical homeostasis by clearing excess neurotransmitters, redistributing potassium and supplying metabolic substrates. Oligodendrocytes influence axonal conduction by myelination, while microglia contribute to local neurochemical balance via receptor-mediated uptake and enzymatic degradation of signalling molecules. Together, this intricate network of transmitters, receptors and supporting cells shapes information processing in health and underlies diverse pathological states when disrupted.

Research from Nature Portfolio

Recent work has shown that astrocytes and perineuronal nets collaborate to confine synaptic signals within cortical microcircuits. Fine gaps in the net lattice mark sites where tripartite synapses—pre- and post-synaptic specialisations and astrocytic processes—co-localise glutamate and GABA transporters, preventing neurotransmitter spill-over and maintaining excitatory–inhibitory balance. Complementing this, a molecular study of glycosaminoglycan assembly has revealed how the enzyme EXTL3 selectively initiates heparan sulphate chains on core proteins, whereas CSGALNACT2 acts by default to kindle chondroitin sulphate. These distinct decision points in glycosaminoglycan biosynthesis shape extracellular chemistry and influence synaptic plasticity by tuning the charge and porosity of the neurone’s pericellular coat.

Cell Neurochemistry publication trend

The graph below shows the total number of articles in cell neurochemistry across all publications each year (not limited to Nature Index journals).

Technical terms

Perineuronal nets (PNNs): Specialised extracellular matrix structures composed of chondroitin sulphate proteoglycans that wrap around neuronal somata and stabilise synapses.

Glycosaminoglycans (GAGs): Long, unbranched polysaccharide chains that attach to core proteins, conferring charge and binding sites within the extracellular matrix.

Microdialysis: A sampling technique that perfuses a semipermeable probe within tissue to collect extracellular fluid for chemical analysis.

Droplet microfluidics: The use of micro-channels to segment continuous fluid streams into discrete droplets, enabling compartmentalised transport and analysis.

Electroosmotic perfusion: A method that applies an electric field to drive fluid through tissue, allowing delivery and recovery of analytes without pressure-driven flow.

Tripartite synapse: A functional unit formed by pre- and post-synaptic neuronal elements together with an associated astrocytic process.

Neurochemical monitoring: The real-time measurement of neurotransmitters, neuropeptides or ions in living brain tissue to study dynamics of cell signalling.

References

1. Astrocytes require perineuronal nets to maintain synaptic homeostasis in mice. Nature Neuroscience (2024).
2. Molecular mechanism of decision-making in glycosaminoglycan biosynthesis. Nature Communications (2023).
3. Microdialysis coupled with droplet microfluidics and mass spectrometry for determination of neurotransmitters in vivo with high temporal resolution. Analyst (2024).
4. Electroosmotic Perfusion, External Microdialysis: Simulation and Experiment. ACS Chemical Neuroscience (2023).
5. Integrated sampling-and-sensing using microdialysis and biosensing by particle motion for continuous cortisol monitoring. Sensors & Diagnostics (2023).