Dopaminergic Neurons Differentiation Service

Overview of Dopaminergic Neurons

Fig.1 Molecular factors involved in the development of ventral midbrain (VM) Dopaminergic (DA) neurons.¹

Previous research has shown that the hypothalamus and substantia nigra are the main sources of dopamine production in the brain. In adult mammals, dopamine synthesized in the hypothalamus, mostly in neurons that localized in the insert zones, the periventricular and arcuate nuclei, is involved in neuroendocrine regulation as a) a neurotransmitter controlling the secretory activity of peptidergic target neurons, b) a neuromodulator regulating the release of neurohormones from neighboring peptidergic axons into the median eminence, and c) a neurohormone passing via the hypophyseal portal circulatory system to the anterior lobe of the hypophysis, where it inhibits prolactin secretion.

Dopaminergic Neurons and Parkinson's Disease (PD)

The depleted dopamine levels, dopaminergic neurons loss, and intraneuronal cytoplasmic inclusions termed as Lewy Bodies (LB) in surviving substantia nigra pars compacta (SNpc) neurons are the pathological hallmarks of PD. The SNpc contains the soma of nigrostriatal neurons and projects them to the putamen. The pattern of SNpc cell loss appears parallel to the expression levels of the dopamine transporter (DAT) transcript and is consistent with the finding that dopamine loss is most pronounced in the dorsolateral putamen, the main site of projection for these neurons. At the onset of symptoms, putamen dopamine is depleted 80%, and 60% of SNpc dopaminergic neurons have already been lost. However, the cell bodies of mesolimbic dopaminergic neurons adjacent to SNpc are affected to a limited extent in PD. Consequently, there is significantly less depletion of dopamine in the caudate. Thus, the selective loss of dopamine in the striatum primarily contributes to PD pathology.

Services at Creative Biolabs

During years of exploration in neural differentiation models, Creative Biolabs has developed a comprehensive technology platform with a variety of available models. Our platform is now equipped with advanced facilities, experienced experts, and the latest technologies. With these strong foundations, we are confident in offering custom dopaminergic neurons differentiation model services to global clients.

If you are interested in custom dopaminergic neurons differentiation model services, or any other neural differentiation models, please feel free to contact us for more information.

• Dopaminergic neurons correspond to approximately 3-5% of total neurons in the substantia nigra.
• Dopaminergic neurons play a significant role in the cardiovascular, renal, hormonal, and central nervous systems.
• Dopaminergic neurons are thought to control processes as diverse as movement and drug addiction.
• An excessive amount of dopamine in the brain is affiliated with schizophrenia characterized by altered behavior and delusions.
• Dopamine deficiency in the substantia nigra in aged populations results in PD which constitutes a major public health burden in westernized countries where the average life expectancy is 85 years or greater.

Our service would primarily focus on the production and specialization of dopaminergic neurons for various research purposes. Our end-to-end service platform optimizes every step from inducing differentiation to final cell analysis, providing high-yield, high-purity, fully functional dopaminergic neurons ready for your downstream applications.

We also offer flexibility in our services, including but not limited to:

Published Data

Chen, Yalan et al. optimized the in vitro differentiation protocol for dopaminergic neurons. In their study, three different dopaminergic neuron differentiation schemes were constructed in vitro using a combination of dual inhibitors of SB431542 and dorsomorphin, a combination of SHH and FGF8, and a combination of CHIR, SHH and FGF8. The results showed that the combination of CHIR, SHH and FGF8 induced neural differentiation and produced a high percentage of dopaminergic neurons.

The figure below shows electrophysiological assays of neurons induced by the CHIR + SHH + FGF8 induction protocol, including sodium current parameters recorded from dopaminergic neurons, a schematic of sodium current distribution, and representative images. The neurons exhibited characteristics consistent with dopaminergic neuron subtypes.

Fig. 2 Electrophysiological properties of dopaminergic neurons derived from the CHIR + SHH + FGF8 induction protocol.²

Applications

We leverage state-of-the-art technology for the differentiation of iPSCs into dopaminergic neurons. Our proprietary techniques ensure a high yield of healthy, mature, and functional neurons for use in research or therapeutic development.

• Application in Drug Development: Our service can facilitate CNS drug discovery and development, as the differentiated cells can be used for screening potential drug candidates, especially those targeting neurodegenerative diseases.
• CNS Disease Modeling: The dopaminergic neurons differentiated through our service can be used to construct disease models, particularly for conditions like Parkinson's Disease, which can help elucidate disease mechanisms and guide treatment development.
• Therapeutic Development: Our differentiated dopaminergic neurons can potentially be used in regenerative medicine research. Specifically, for cell replacement therapies in patients with Parkinson's Disease and other disorders affecting dopaminergic neurons.

FAQs

• Q: Can you assist researchers in characterizing the functional properties of differentiated dopaminergic neurons, such as neurotransmitter release and electrophysiological activity?
  A: Absolutely. Characterizing the functional properties of differentiated dopaminergic neurons is an essential aspect of our service. We offer assistance and expertise in conducting various functional assays to assess neurotransmitter release, electrophysiological activity, calcium imaging, and other functional parameters. Our team provides guidance on experimental design, data analysis, and interpretation to ensure comprehensive characterization of the differentiated neurons and facilitate meaningful insights into their functionality.
• Q: What type of progenitor cells can I use for this service?
  A: Our dopaminergic neuron differentiation service is compatible with a variety of progenitor cells. This primarily includes embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). It can also be applied to neural progenitor cells under certain circumstances.
• Q: How do you deliver the differentiated neurons?
  A: The differentiated dopaminergic neurons will be harvested, counted, and packaged in a sterile, temperature-controlled environment to ensure their viability. The cells will then be shipped overnight to your designated location to ensure they arrive in the best possible condition for your experiments.
• Q: What kind of post-purchase support do you provide?
  A: We provide extensive after-sales support. This includes guidance on handling and culturing the neurons, troubleshooting for any problems you might encounter, and further consultations if you require modifications or adjustments for future projects. Our team of experts is always available to assist with your research needs.

Scientific Resources

Neurotrophic Factors and Neural Differentiation

References

1. Hegarty, S. V.; et al. Midbrain dopaminergic neurons: a review of the molecular circuitry that regulates their development. Dev Biol. 2013, 379(2): 123-38.
2. Chen, Yalan, et al. "Multiple factors to assist human-derived induced pluripotent stem cells to efficiently differentiate into midbrain dopaminergic neurons." Neural Regeneration Research 19.4 (2024): 908-914.

For Research Use Only. Not For Clinical Use.