Central Nervous System Diseases and BV-2 Cell Lines

Author: AcceGen R&D Team

Introduction

Nervous system diseases, especially central nervous system (CNS) diseases, have always been a thorny problem in clinical medicine and a research hotspot in basic medicine and physiology. As a key component of the CNS, microglia play key roles in CNS diseases, which is the research focus of CNS diseases. And microglia are active participants in brain function and brain dysfunction. Therefore, familiarity with BV-2, the most classic microglial cell model in vitro, will be of great help to researchers.

Overview: Nervous System and Glia

The nervous system is a highly complex key system that controls the actions, behaviors, physiological activities, and transmission of perceptual signals of the host. And it also plays a role as environmental adaptation regulators work in tandem with the endocrine system[1]. The nervous system includes the central nervous system (CNS) and the peripheral nervous system (PNS). The CNS is the most important part of the nervous system, consisting of the brain and spinal cord. And it is the central coordinator of the peripheral signal and the controller of the global physiological processes[2]. The PNS refers to the nerves and ganglia outside the brain and spinal cord, which play roles in the transmission of perceptual signals and regulation signals. And it consists of the somatic nervous system and the autonomic nervous system[3].

Glial cells (also called neuroglia) are the maintainer and protector of global physiological homeostasis and the nervous system[4; 5]. Glial cells can be divided into macroglia and microglia. Macroglia mainly include astrocytes (CNS), oligodendrocytes (CNS), ependymal cells (CNS), radial glia (CNS), Schwann cells (PNS), satellite cells (PNS), and enteric glia cells (PNS). These cells have different functions, such as blood supply regulation[6], providing insulation to the axon[7], the creation and secretion of cerebrospinal fluid[8], immunomodulation[9], the external chemical environment regulation of neurons[4], etc. Microglia are macrophages that can maintain and protect neurons located in the CNS[10]. Microglia are the primary immune cells of the CNS, which show an indispensable role in the first and main form of active immune defense[11].

Microglia and CNS-related pathology mechanism

Microglia are distributed in the whole brain and spinal cord, accounting for 10%~15% of the cells found in the brain[12]. Microglia are macrophages resident in the CNS and highly sensitive to lesions, which can timely and accurately remove plaques, damaged or useless neurons, and infectious pathogens[13; 14]. Besides, microglia also show key functions in extracellular signal transduction, which makes it become one of the core elements that must be paid attention to in CNS-related physiological and pathological processes[15]. Corresponding to the pathological changes of the CNS, microglia produce persistent morphological and physiological changes (Figure.1)[16].

In acute CNS damage, microglia show chemotaxis of the tissue damage site, prompting microglia to converge toward the damage site[17]. This protective effect of microglia depends on its tile-like network covering the entire neuropil under tightly regulated[18]. As immune cells (macrophages), microglia can secrete cytokine to involve in the inflammatory immune response of the CNS[19]. And microglia phagocytosis disorder is the cause of some CNS diseases[20]. Besides, microglia can be identified as direct cause of primary microgliopathies. The pathological mechanism is usually the physiological or morphological abnormality of microglia caused by a mutation[21].

Immortalized Microglia In Vitro Model: BV-2 Cell Lines

Microglia in vitro models are essential tools for the research of physiological functions and diseases of the CNS, such as peripheral macrophage-induced microglia, primary microglia, immortalized cell lines, pluripotent stem cell-derived microglia, and cerebral organoids[22]. Immortalized microglial cell lines are the most commonly used thanks to their easy cultivation and cheap application. The construction methods of immortalized microglial cell lines mainly include oncogene or SV40 large T antigen transduction, and one of the most classical cell lines is murine cell line BV-2[23; 24].

Murine immortalized microglial cell line BV-2 has been established for several decades, which is one of the most classical and commonly used immortalized cell lines and in vitro microglia models. It is generated by transducing v-raf/v-myc oncogene into primary microglial cells by a retrovirus [24]. The culture methods of BV-2 are very convenient. The recommended culture methods of BV-2 are DMEM with 10% FBS, 1% P/S and 1.1% GlutaMax (Substitute of L-glutamine) and culture at 37℃ with 5% CO₂. And the recommended culture density of BV-2 is not exceeding 5 × 10⁵ cells/ml[25].

Application of BV-2: The mechanism of chronic pain

Chronic pain seriously affects the quality of daily life of patients, and neuroinflammation in the spinal cord is a major cause of chronic pain. Qian, et al. revealed the role of K_ATP channels in neuroinflammation and chronic pain, and BV-2 cell line is an in vitro model in this work[26]. In the beginning, they found the cromakalim-induced opening of K_ATP channels can alleviate postoperative pain through animal models. After RNA-seq analysis of Cromakalim treatment, they found that the differentially expressed genes were enriched in inflammation-related signal and upregulation of suppressor of cytokine signaling-3 (SOCS3). And then, based on BV-2 as an in vitro model and combined with an in vivo mouse model, they identified that the opening of K_ATP could activate Growth arrest-specific 6 (Gas6)/Axl signal to induce the expression of SOCS3 and then induced the inflammation tolerance to inhibit the neuroinflammation-induced chronic pain.

Conclusion

CNS-related diseases and physiological processes are a long-term hot area. Microglia play key roles in CNS-related physiological and pathological processes, which makes the number of publications rapidly climb year by year. And BV-2 cell line as a classical in vitro model of microglia provides a great help to the rapid progress of microglia-related fields in recent decades.

Where to Get BV-2 Cell Line for Your Research?

AcceGen cultures and provides BV-2 cell line isolated from C57BL/6 mouse brain and transformed by a recombinant retrovirus (v-raf/v-myc) for neurobiology research. To get more information, please refer to: Tumor Cell Lines.

It is our pleasure to help relative researches to move forward. All the products of AcceGen strictly comply with international standards. For more detailed information, please visit our product portfolio or contact inquiry@accegen.com.

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