Striatal Neurons Differentiation Service

With years of experience in neuroscience and our most devoted scientists, Creative Biolabs has gained significant knowledge in stem cell-based models for neuroscience research. We are confident in delivering striatal neurons differentiation models that can meet your specific requirements.

Introduction to Striatal Neurons

The striatum is the component of the basal ganglia and a key neural substrate for procedural learning and memory. The striatum receives afferents from cortical areas, processes motor and associational cortical information, and passes to the output nuclei of the basal ganglia. Four putative types of striatal neurons are medium spiny, fast-spiking, tonically active, and low-threshold spiking.

• Regions of Striatal Neurons

The striatum is divided into ventral striatum and dorsal striatum subdivisions based upon function and connections in primates. The ventral striatum is composed of nucleus accumbens and olfactory nodules. The dorsal striatum is composed of the caudate nucleus and the laterally positioned putamen. The ventral striatum primarily mediates reward, cognition, reinforcement, and motivational salience. In contrast, the dorsal striatum primarily mediates cognition involving motor function, certain executive functions (e.g., inhibitory control and impulsivity), and stimulus-response learning.

Fig.1 Cell types and functional organization of the rodent striatum.¹

• Striatal Neuromodulators

Striatal functions are mediated by the medium-sized spiny neurons (MSNs), which are the projection neurons of the striatum. The remaining striatal neurons are made up of four different types of aspiny interneurons. MSNs, which use γ-aminobutyric acid (GABA) as a transmitter, are born in the ventricular/subventricular zones of the lateral ganglionic eminence and migrate to the striatum. They are divided into two equal-size populations: (1) The activation of the direct pathway can lead to the start of movement under normal circumstances. (2) The activation of the indirect pathway can lead to the opposite physiological effects.

Recent studies show that striatal neurons are dependent on neurotrophins for their proper function. Brain-derived neurotrophic factor (BDNF) and signaling play an important function in normal and pathological conditions, such as promoting somatic growth, dendritic complexity, and spine density in striatal neurons. In addition, one of the striatal neuromodulators is dopamine plays a fundamental role in normal basal ganglia function and movement. Dopamine signaling is implicated in reinforcement learning. Moreover, acetylcholine represents a second major striatal neuromodulator released into the extracellular space by tonically active cholinergic interneurons.

Fig.2 Dopaminergic and cholinergic modulation of striatal neurons.¹

• Functions of Striatal Neurons

Functionally, the striatum coordinates multiple cognition aspects, including motor and action planning, decision-making, motivation, reinforcement, and reward perception. The striatum participates in social processes related to reward inequity and observation and learning in humans. Some striatal neurons coded social action without coding reward. Emerging evidence shows that MAPK-mediated genomic responses in striatal neurons to drug exposure contribute to the development of neuroplasticity related to addictive properties of drugs of abuse.

• Diseases Related to Striatal Neurons

Diseases of the striatum include Parkinson's disease (PD) and Huntington's disease (HD). PD results in loss of dopaminergic innervation to the striatum and a cascade of consequences. Dysfunction and death of striatal neurons are the main causes of the motor disorders associated with HD. Although general brain atrophy is found in HD patients, the striatum is the most severely affected region. In addition, some disorders arise through the overexpression of factor genes in the striatal neurons, including addiction, bipolar disorder, autism spectrum disorder (ASD), dysfunction (depression and obsessive-compulsive disorder). Striatum also involves some movement disorders such as chorea, choreoathetosis, and dyskinesia.

Striatal Neurons Differentiation Service

Creative Biolabs is experienced in the custom neural differentiation service based on our STEMOD™ ex vivo models. The top research team in Creative Biolabs can provide customers time- and budget-saving striatal neurons differentiation services. Induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs), for example, can be recently used as starting cells for striatal neuron differentiation. Striatal differentiation could be promoted by using a combination of growth factors, morphogens, neurotrophins, and small-molecule inhibitors and analogs. Also, the differentiated neurons can be extensively characterized based on our well-established technology platform. Our multistep differentiation protocol presents a reliable and simplified method for generating striatal neurons, yielding a critical resource for neuronal physiology, the study of neurodegenerative disorders, a model system for drug discovery.

As a global leader of ex vivo models, Creative Biolabs provides a range of neural differentiation services regarding our STEMOD™ ex vivo models. Please do not hesitate to contact us or reach us by e-mail or phone with your particular needs.

Our striatal neuron differentiation service is a specialized process that we offer to research institutions, pharmaceutical companies, and other biotech firms who wish to study diseases that affect the striatum region of the brain, such as Parkinson's disease or Huntington's disease. This service involves

• The generation of mature, fully functional striatal neurons from pluripotent stem cells
• Strict quality control measures
• Cryopreservation and delivery of ready-to-use neurons
• Neuron culture media and related reagents

We work closely with our clients to ensure that they get the results they need. This means offering custom service packages designed to meet the precise needs of each client, from small academic institutions to large pharmaceutical companies.

By rendering this service and related services, we aim to accelerate research and drug discovery in neurodegenerative diseases that affect the striatum, including but not limited to:

Published Data

Naoya Amimoto et al. established a robust protocol for generating striatal MSNs from hiPSC by transient combinatorial modulation of extrinsic signals using various small molecules in 2D culture. In subsequent experiments, they modified the protocol to drive striatal self-organization using a rapid repolymerization (SFEBq) approach. In 2D and 3D cultures, they examined the labeling of lateral ganglionic elevation (LGE) progenitors, striatal MSN, and neurospheres during differentiation.

As shown, their multiple gene expression profiling using qPCR showed expression analysis of iPSC genes, neural/neuronal genes, LGE genes, and striatal genes at days 0, 17, 28, and 56. They concluded that the combination of small molecules in the protocol is sufficient to generalize the signaling patterns during striatal development.

Fig. 3 Generation of striatal neurons from hiPSCs.²

Applications

Researchers and biotech companies can utilize our differentiated striatal neurons for a wide range of applications, including:

• Disease Modeling - Researchers can induce disease-specific genetic mutations or expose the cells to neurotoxins to mimic pathological conditions, allowing for the study of disease mechanisms and the screening of potential therapeutic compounds.
• Drug Discovery and Development - The use of hiPSC-derived striatal neurons in drug discovery programs enables high-throughput screening of small molecules, biologics, and gene therapies for their efficacy in modulating disease-relevant phenotypes.
• Mechanistic Studies - Researchers can utilize advanced imaging techniques, transcriptomic analysis, and biochemical assays to elucidate signaling pathways, synaptic connectivity, and neurodegenerative processes within the striatum.

FAQs

• Q: What techniques do you utilize to ensure the purity of the differentiated striatal neurons?
  A: To ensure purity, we utilize a combination of immunocytochemistry and molecular biology techniques. Immunocytochemistry allows us to stain for specific neuronal markers characteristic of striatal neurons, enabling us to visually confirm their identity under a microscope. Additionally, we perform gene expression analysis using techniques such as qRT-PCR to verify the expression of key striatal neuronal markers at the molecular level, ensuring the absence of contaminated cell types.
• Q: Can these differentiated neurons be used in a clinical setting?
  A: Currently, our differentiated striatal neurons are intended for experimental use in a research setting. They are not intended for clinical diagnosis or treatment.
• Q: What is the expected viability and shelf life of the differentiated striatal neurons upon delivery?
  A: Upon delivery, the differentiated striatal neurons typically have high viability and can be maintained in culture for an extended period, depending on the specific experimental conditions and culture protocols used. While we cannot guarantee a specific shelf life due to variability in culture conditions and handling practices, we provide detailed instructions for optimal culture maintenance to maximize the viability and longevity of the differentiated neurons.
• Q: Can you provide support for downstream applications?
  A: Yes, we can provide support for downstream applications such as in vivo transplantation studies or co-culture experiments involving pluripotent stem cells-derived striatal neurons. Our team of scientists has expertise in a wide range of experimental techniques and can offer guidance on experimental design, protocol optimization, and troubleshooting for these applications. Whether you are interested in transplanting the differentiated neurons into animal models or co-culturing them with other cell types, we can provide the support you need to achieve your research goals.

Scientific Resources

Neurotrophic Factors and Neural Differentiation

References

1. Kreitzer, A. C. Physiology and pharmacology of striatal neurons. Annual review of neuroscience. 2009, 32, 127-147.
2. Amimoto, Naoya, et al. "Generation of striatal neurons from human induced pluripotent stem cells by controlling extrinsic signals with small molecules." Stem Cell Research 55 (2021): 102486.

For Research Use Only. Not For Clinical Use.