# PC12 and THP-1 Cell Lines as Neuronal and Microglia Model in Neurobiological Research
## 1 Introduction  
in vitro studies and, in particular, cell models have become an inseparable part of modern scientific research on new drugs and treatments. Cell cultures are a reliable tool that, if handled correctly, constitutes an irreplaceable supplement to biochemical testing and experiments on rodents. The in vitro studies on cell cultures also provide great insight into prevention, progression and potential causes of various diseases, including, e.g., neurodegenerative disorders, tumors or other disorders resulting from a genetic predisposition. As a result, these studies make it possible to discover new, more effective therapies [1, 2]. Main applications of cell cultures in scientific studies include:  
* Screening for toxicity in pharmacological studies of newly synthesized drugs and discovered natural substances prior to in vivo testing;
* Studying the effect of drugs on tissues, cells and their organelles;
* Studying pathways and pathophysiological mechanisms involved in disease onset and progression;
* Production of specific proteins or cellular substances, which are not yet obtained in recombinant form;
* Microbiology and virology (mainly multiplication of intracellular pathogens). Increasing pressure is put on creating well-defined, standardized cell models. Primary cultures based on mature cells are usually hard or even impossible to obtain. Therefore studies are usually conducted on cancer-derived cell lines induced to differentiation or otherwise stimulated to acquire the desired phenotype. Cultures gradually become more sophisticated and structurally complex--for example, cultures in the form of spheroids or cultures on microcarriers such as dextran, gelatin or glass beads. Co-cultures of different cells can serve to derive an even closer model of real human tissues, organs or systems, with the physiological and pathophysiological cross-talk between different cell types and the exchange of bioactive compounds and stimuli. A wide range of available cell lines and the possibility of their differentiation and targeted modification with environmental factors or various cytokines and stimulants allow for the appropriate adjustment of the cell model to reliably test the assumed hypothesis [1]. On the other hand, the lack of standardization in selecting and treating cell cultures is one of the main factors responsible for the poor reproducibility of various studies [3]. Therefore, proper preparation of cell lines, including necessary differentiation, should always be considered in planning a new study (Table 1). Alzheimer's disease (AD) is a neurodegenerative disorder and, in its sporadic/late-onset (LOAD) form, is the main cause of dementia in patients over 65 years old. Pathophysological hallmarks of AD include extracellular amyloid \(\beta\) (A\(\beta\)) deposits in the form of senile plaques and intracellular neurofibrillary tangles (NFTs) comprised of hyperphosphorylated tau protein. These histological changes are often accompanied by chronic neuroinflammation with persistent activation of microglia and astrocytes [4; 5; 6]. Even though the disease has been known for more than a century, the exact molecular pathmechanism of this neurodegenerative disorder and the factors triggering AD onset are yet to be elucidated. Neuroinflammation is a complex and multidimensional phenomenon involving various cells that affect many extra- and intracellular signaling pathways and cytokine production [7]. The macrophages of the brain (microglia) are the main agent of innate immunity in the central nervous system (CNS) and perform various functions, ranging from protective to even harmful, in response to received signals [8; 9]. Their activation for a short period as a response to an acute pathological state is beneficial, but chronic microglial activation inevitably leads to neuroinflammation, neuronal death and cognitive decline observed in AD [4; 5; 10; 11; 12; 13]. Neurobiological studies on cell cultures mostly rely on PC12, SH-SYSY, P19 and Neuro-2a continuous cell lines as neuronal models.