Neurochemistry: Neuroendocrine Immune System Modulation & Brain Function
The neuroimmunology knowledge base can be used in the understanding of bidirectional neural-immune interactions, which comprises of complex systems that are normally interacting at many levels. The neuronal and neuroendocrine pathways play a role in controlling of cellular and humoral immune responses. Recent studies have, however, shown how the immunity is suppressed by neurons in parasympathetic nervous system and which secrete acetylcholine. Cytokines is the primary means through which the central nervous system is influenced by the immune systems as a result of this suppression (Ader, 2007). Molecules of neuro- and immune signal which include the hormones, cytokines or their receptors belong to one big family and this enables a neuro-immune communication that is mutual. The immunoenehancement which comprises of antitumor and antiviral cytotoxic acitivity and which relates to the reward system of the brain provides directions for immune disorders found therapy (Galimberti & Scarpini, 2014).
Inside the brain, the inflammation as common disease mechanism has various benefits in that it drives responses of the brain to dangerous stimuli. This beneficial process may at times go off balance and thus leading to the persistence of neuroinflammatory process. Hence, it has become possible to relate the damage progression in some neurodegenerative diseases to chronic neuroinflammation that has not been controlled. The basis of this association includes pathophysiology and levels of pro-inflamnatory cytokines. The AD is normally driven by the accumulation of intracellular tau protein and the deposition of extracellular beta amyloid compounds that are insoluble (Griffin, 2006). Amyloid forms the main element of senile plaques while tau is an element of neurofibrillary tangles. The deposition of amyloid is usually specific for AD and is considered to a possible primary. Beta amyloid is toxic to body neurons. In the preparation of brain slice, it leads to a long term potentiation, killing neurons and damaging the synapses. There is also selective neurotoxicity for both the entorhinal cortex (an area that seriously affected by the diseases) and hippocampus and spares the cerebellar neurons (Griffin, 2006). The damage is made possible by free radicals that arise from the combination of amyloid with zinc, copper and iron ions. A high correlation exists between the severity of neurological dysfunction in the diseases and the soluble amyloid solution. The AD has two major lesions – Alzheimer’s plaques (or senile plaques –SPs) and the nuerofibrillary tangles. The Alzheimer’s plaques are spherical lesions found in cerebral cortex and are of two kinds which are diffuse amyloid plaques and neuritic plaques. The neuritic plagues are diffuse amyloid plaques that contain neuronal processes that are degenerating and with tau paid helical filaments (Griffin, 2006).
The Alzheimer’s disease has been linked to chronic neuroinflammation. There has been established a strong link between the neurodegeneration and pro-inflammatory cytokines, which has been found in both bench research and clinical data. The cytokines acts as soluble cell communication mediators that are essential in immune regulation and the bidirectional communication between the immune system’s cells and the nervous systems cells (Dunn, 2006). In addition, if cytokines is increased as a result of maternal infection, an alteration may occur on the immune status of a child’s brain leading to the development of abnormal cells subsequent damage of the brain. It is evident that activation of maternal immune result to a rise of cytokines level in the placenta and the amniotic fluid. The effects of cytokines on the placenta can change the transmission of cells, oxygen, growth factors, nutrient and maternal antibodies and each of these can affect the development of the fetus (Ader, 2007).
Glioblastoma Multiforme refers to an aggressive type of brain tumor whose cures are very few. Glioblastoma is the most primary and deadly tumor of the brain which primarily arises from epigenetic and genetic astroglial cells alterations. Activator and signal transducer of transcription 3 which is referred as STAT3 is the primary potent gliomagenesis regulator which is achieved through angiogenesis induction, invasion of tumor and immunosuppression host (Ader, 2007). In the cells of Glioma the mutations gain leads to STAT3 activation which makes cancer therapy inhibition process to be more attractive. The other potential target is the GBM molecular therapy which works through resistance of treatment as well as an occurrence. The molecular is from the proteins family which mediates the transcription of nuclear (Ader, 2007). The molecular pathogenesis of glioblastoma involves both the gain and loss of proteins that causes the multiplication and proliferation of tumor cells .A major increase in the protein level in the glioblastoma as compared to other grades of glioma indicates that alterations pattern are likely consist of many cellular pathways and regulatory system of the molecular in tumor cells that are aggressive. Essentially, glioblastoma is a clinical entity that has anaplastic satrocytoma and astrocytoman and pathologically it may at times arise from an astrocytic tumor that is less anaplastic and may also consist of neoplastic astrocytes. Therefore, it is an astrocytes’ tumor. The World Health Organization classifies bthe glioblstoma as central nervous system tumor that is poorly differentiated and is not referred as part of astrocytic neoplasm. The glioblastoma histological diagnosis is normally made on two secondary features basis but not certain cytological characteristics (Griffin, 2006). The said features are necrosis and vascular proliferation.
The interactions between cytokines and the nervous system happen in various ways. The cytokines molecules play a significant role in the survival or death of neuronal cell. Moreover, the peripheral cytokines that are released from immune cells due to inflammation can lead to various neuroendocrine responses of the central nervous system. The immune system is, in turn, regulated by the nervous system through various routes that include the neuroendocrine pathways and the peripheral and autonomic nervous systems (Dunn, 2006). Experiments have been done to show the extent to show how cytokines together with their receptors are indicated in the tissues of the nervous systems and how much the tissues resoond to the cytokines. These experiments have involved the immunohistochmeistry to show the cytokine pathways in central nervous system. The pattern of specific cytokines over expression in human brain of infected patients shows that cytokines neurotoxic effect has a role in the neurodegenerative diseases in human. Immunomodulation is aimed at manipulating the immune systems to keep infections under control and immunomodulatory molecules can modify immune systems and include immunomodulators like cytokines (Pirtoli, Gravina & Giordano, 2016). Cytokines can be viewed as immunomodulators. Pharmacogenomics refers to the field of research that is aimed at understanding the way in which genetic factors influences selective therapies choice and affect the reponse to human infections treatment responses. Currently available knowledge on degenerative disorders and which are erratic indicates that in spite of their multifactorial etiopathogenesis, genetics have a major role in causing pathological events. Treatments of such infections involve an interaction between a stimulus that are administered exogenously and various endogenous proteins that form part of disease pathogenesis. Such an interaction takes place between neutotransmitter and an exogenous molecule that is capable of blocking this interaction (Pirtoli, Gravina & Giordano, 2016).
There is an increasing interest in the trails of non-pharmacological which has been supported by the use of electrophysiological techniques. Various strategies that have been used to study the manner in which brain circuit works include deep simulation of the brain, stimulation of spinal cord and the peripheral nerve which the researchers also use as a form of treatment. Studies have shown that the amount of peripheral immune cells detected in the central nervous systems can result from irradiation and not pathological physiology (Pirtoli, Gravina & Giordano, 2016). Evidence from such studies have indicated that the presence of bidirectional communication between the immune system and the brain. Furthermore, physiological stressors can affect the immune function. As such stress associated with taking care of people with Alzheimer’s disease or even depression has been linked to measures of reduced immune responses. Moreover, information on how brain affects immune responses has been gotten from lesion studies (Galimberti & Scarpini, 2014). In the event of immune responses, certain automatic nuclei show electrical activity that has been altered and varied monoamine metabolism which suggest that a reciprocal communication between the brain and the immune system. The immune system can communicate with central nervous system through the outflow of endocrine from the nervous system. Cytokines can also transmit some signals to the central nervous system from the immune system. This communication may indicate an immunoregulatory function on the part of the brain and sensory role on the part of immune system (Galimberti & Scarpini, 2014).
Molecular pathways result from excessive and abnormal messages that are translated to the endothelial cells which eventually lead to ineffective and chaotic blood flow. This determines the acidosis and hypoxia areas in the tumor. Acidosis and hypoxia belong to the most potential stimuli for the production of pro-angiogenic cytokine which lead to more pathologic loop and thus sustaining the emergence of glioblastomas (Pirtoli, Gravina & Giordano, 2016). A significant result of this environment that is highly pathological is the more resistant and malignant tumor cells which can make them lose apoptotic reaction to hypoxia. The Alzheimer’s pathways include the amyloid cascade hypothesis that relate to the genes. The AD involves protective variants that can be seen in amyloid gene and has low risk and high risk variants for the condition. The variants have been found in the amloid response pathways. The amyloid hypothesis holds that deposition of beta amyloid initiates the various events that eventually lead to AD (Pirtoli, Gravina & Giordano, 2016). The accumulation of beta amyloid in the brain serves as the main driving force behind the disease’s pathogenesis. Other pathways include the signal pathways that form crucial part of the intra and inter-cellular signaling. These pathways allow for enable cells to transport, receive and act on various molecular signals. Research has found protein –to- protein networks interactions for the Alzheimer’s disease (Pirtoli, Gravina & Giordano, 2016). This research explored the relationship between the AD and the interaction of proteins by use of these proteins structural analysis.
In normal cells, genomic integrity is maintained by telomeres and chromosomal instability is stimulated by continuous division of cells. In most of the cancer cells, the telomerase sustains the length of telomere. The length of telomere and the activity of telomerase play significant role in the development of cancer and growth of the tumors. The telomerase serves as the ribonucleoprotein enzyme where it catalyzes the telomeric DNA extension in a eukarytic organism (Jafri, Ansari, Alqahtani & Shay, 2016). The telomerase in human comprises of hTR , hTETY and the dyskerin proteins , NHP2, GAR1 and the NOP10. The activation of telomerase in the cancer cells resulting to recurrent mutations that generate a 11bp nucleotides stretch that is identical and which have a consensus binding pattern. Such a motif serves the role of transcritptional repressors and regulates expression of telomerase (Jafri, Ansari, Alqahtani & Shay, 2016). Recently there have been advances in the determination of the ciliate telomerase and yeast structure though there lacks a clear understanding of the role of telomerase in cancer cells of human. However, knowledge about the role of telomerase’s alternative lengthening has increased considerably. There are various beliefs on the mutations of hHERT promoter where some believe it to be the driving force behind carcinogenesis while others believe such mutations only allow the sustenance of tumor growth (Jafri, Ansari, Alqahtani & Shay, 2016).
Developments in pharmacogenomic drugs is capable of advancing the understanding of drug metabolism and interactions, which may lead to drugs that are less dangerous but effective. Producing drugs and delivering them on the basis of efficient and rational application of proteomic and genomics knowledge can be used as a basis of providing a niche that is profitable and involving large amounts of money (Husick, 2012). Such a production would have to involve the identification of various diseases based on specific regions and engaging in personalized medicine strategy. Personalized medicine involves a therapy which uses a treatment approach that is patient focused. This approach allows a drug effect that is more specific and which equates to an adverse event profile that is safer (Husick, 2012).
There have been recent advances in understanding the response of immune system in the central nervous system and that cytokines play a role that extend outside immune response. Given that this involves the behavior modulation and changes in development comes with new perspective on the function of the brain, there is a need for further research on the mechanisms of brain diseases and dysfunction. The future research should also involve the role of cytokines signaling in the alterations of emotions and behavior.
References
In Galimberti, D., & In Scarpini, E. (2014). Neurodegenerative diseases: Clinical aspects, molecular genetics and biomarkers. 214-221
Ader, R. (2007). Psychoneuroimmunology. Amsterdam: Elsevier/Academic Press.422-423
In Pirtoli, L., In Gravina, G. L., & In Giordano, A. (2016). Radiobiology of glioblastoma: Recent advances and related pathobiology.
Griffin, W. (2006).Inflammation and neurodegenerative diseases. American Journal of Clinical Nutrition. Retrieved from: http://ajcn.nutrition.org/content/83/2/470S.full
Dunn,A.(2006).Effects of cytokines and infections on brain neurochemistry. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2136407/
Jafri, M., Ansari, S.,Alqahtani,M. and Shay,J.(2016). Roles of telomeres and telomerase in cancer, and advances in telomerase-targeted therapies. Retrieved from: https://www.ncbi.nlm.nih.gov/pubmed/27323951
Husick,L.(2012).Planning for Personalized Medicin.Managing Innovation in the Life Science. Retrieved from: http://advanced.jhu.edu/wp-content/uploads/2013/04/PersonalizedMedicineClassBook.pdf
