We've pulled together the most common markers for mature neurons from the literature, so you can easily select the right one for your experiment.

What are mature neurons?

Mature neurons are terminally differentiated and can no longer divide. They are meant to receive, process, and send information in the central and peripheral nervous systems.

The nervous system is made up of many different types of cells. Neurons are electrically excitable cells with defined compartments, dendrites, soma, axon and synaptic terminal required to transmit electrical and chemical signals. Neuronal identification and studying neuronal subtypes and neuronal identity rely on molecular markers and cell markers, such as cytoskeletal proteins, transcription factors, and secreted factors. These markers are detected by gene expression analysis and by looking at genes that are modulated during neuronal activity. Loss or alteration of neuronal processes like axons and dendrites can be studied using these markers, which is important for understanding neurodegenerative diseases and for selecting mature neuron markers.

Besides neurons, the nervous system has non-neuronal cells that are alongside neurons, primarily glial cells. Glial cells are microglia and macroglia cells, astrocytes, oligodendrocytes, radial glia, schwann cells, and satellite cells. Glial cells provide neurons with trophic and metabolic support, maintain synaptic homeostasis, and modulate neuronal activity, ion homeostasis, and support various neuronal activities like axonal outgrowth and synaptic function. Oligodendrocytes myelinate neuronal axons in the CNS, while Schwann cells do the same in the peripheral nervous system. This complex cellular environment is important for proper nervous system function and that’s why we need to select the right markers for mature neurons.

NeuN

NeuN is an RNA-binding protein that is highly specific for post-mitotic neurons. NeuN is widely used as a mature neuron marker due to its specificity for labeling neuronal nuclei, making it valuable for identifying mature neurons in various brain regions¹. Other mature neuron markers include neuron-specific enolase, which is also used to identify mature neurons in different tissues. However, the following cell types do not express NeuN:

• ​Golgi cells​

• Purkinje cells

• Olfactory bulb mitral cells

• Retinal photoreceptor cells

• Inferior olivary and dentate nucleus neurons

• Sympathetic ganglion cells

Figure 1. Immunohistochemistry (Frozen sections) - Anti-NeuN antibody [EPR12763] - Neuronal Marker (ab177487).

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Microtubule-associated protein 2 (MAP2)

Microtubule-associated protein 2 (MAP2) is a neuron-specific protein that is particularly useful for labeling more mature neurons and promotes the assembly and stability of the microtubule network². MAP2 also plays a role in promoting axonal outgrowth during neuronal development.

Figure 2. Immunocytochemistry/ Immunofluorescence - Anti-MAP2 antibody - Neuronal Marker (ab5392)

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Neurofilament proteins (NF-M and NF-H)

A major intermediate filament found in neurons, 160kDa neurofilament medium, is one of several cytoskeletal proteins present in neurons³.

Figure 3. Immunohistochemistry (Formalin/PFA-fixed paraffin-embedded sections) - Anti-160 kD Neurofilament Medium antibody [EPR23510-76] - Neuronal Marker (ab254348)

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Figure 4. Immunohistochemistry - Free Floating - Anti-Neurofilament heavy polypeptide antibody (ab4680)

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Synaptophysin (SYP)

SYP is a synaptic vesicle protein that is highly concentrated in the synaptic terminal of neurons and regulates vesicle endocytosis⁴. Alternative names include major synaptic vesicle protein p38 and MRX96.

Figure 5. Immunohistochemistry (Formalin/PFA-fixed paraffin-embedded sections) - Anti-Synaptophysin antibody [YE269] - Synaptic Marker (ab32127)

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PSD95

Postsynaptic density protein 95 (PSD95) is a synaptic protein that associates with receptors and the cytoskeleton, and plays a key role in maintaining synaptic homeostasis⁵. This protein has many alternative names, including synapse-associated protein 90 (SAP90) and discs large homolog 4 (DLG4).

Figure 6. Immunohistochemistry (Formalin/PFA-fixed paraffin-embedded sections) - Anti-PSD95 antibody [EPR23124-118] - Synaptic Marker (ab238135).

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Enolase 2 (ENO2)

Enolase 2 (ENO2), also known as NSE (neuron-specific enolase), is a glycolytic enzyme and a widely used marker for immature and mature neurons⁶. During neurodevelopment, ENO2 expression increases as neural progenitor cells differentiate into postmitotic neurons, so it’s a great marker for neuronal lineage commitment. It’s highly enriched in the cytoplasm of developing neurons and is involved in energy metabolism, converting 2-phosphoglycerate to phosphoenolpyruvate in glycolysis.

Beyond its metabolic function, ENO2 has neurotrophic-like properties, supporting neuronal survival, differentiation, and maturation. Its expression is tightly regulated during development and persists in neurogenic regions of the adult brain, such as the hippocampus and olfactory bulb.

ENO2 is also used clinically as a biomarker for neuronal injury and neuroendocrine tumors. Its dual function in metabolism and neurodevelopment makes it a multi-functional marker for identifying immature neurons and studying neurogenesis and neurodegenerative conditions.

Figure 7. Immunohistochemistry (Formalin/PFA-fixed paraffin-embedded sections) - Anti-NSE antibody [EPR3377] - Neuronal Marker (ab79757).

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References

1. El-Husseini, A. E. et al. PSD-95 involvement in maturation of excitatory synapses.  Science  290, 1364–1368 (2000).

2. Kwon, S. E. & Chapman, E. R. Synaptophysin regulates the kinetics of synaptic vesicle endocytosis in central neurons.  Neuron  70, 847–854 (2011).

3. Mullen, R. J., Buck, C. R. & Smith, A. M. NeuN, a neuronal specific nuclear protein in vertebrates.  Development  116, 201–211 (1999).

4. Soltani, M. H. et al. Microtubule-associated protein 2, a marker of neuronal differentiation, induces mitotic defects, inhibits growth of melanoma cells, and predicts metastatic potential of cutaneous melanoma.  Am. J. Pathol.  166, 1841–1850 (2005).

5. Trojanowski, J. Q., Walkenstein, N. & Lee, V. M. Expression of neurofilament subunits in neurons of the central and peripheral nervous system: an immunohistochemical study with monoclonal antibodies.  J. Neurosci.  6, 650–660 (1986).

6. Yuan, A., Rao, M. V. et al. Neurofilaments at a glance.  J. Cell Sci.  125, 3257–3263 (2012).