Glial cell line-derived Neurotrophic factor GDNF Gene Expression Analysis: Unveiling Neuronal Protection Mechanisms in Alzheimer's Disease Management
DOI:
https://doi.org/10.61919/jhrr.v4i2.766Keywords:
Alzheimer's disease, Type II Diabetes Mellitus, Glial Cell Line-Derived Neurotrophic Factor (GDNF), cognitive function, dementia, biomarkers, gene expression, neurodegeneration, Mini Mental State Examination (MMSE), Chemiluminescent Immunoassay (CLIA)Abstract
Background: Alzheimer's disease (AD), accounting for a substantial proportion of dementia cases, presents a formidable challenge to healthcare systems worldwide. The pathogenesis of AD in patients with Type II Diabetes Mellitus (DM) is particularly complex due to the interplay of metabolic and neurodegenerative processes. Understanding the role of Glial Cell Line-Derived Neurotrophic Factor (GDNF) in this context is vital for elucidating potential therapeutic targets.
Objective: This study aimed to assess the expression levels of the GDNF gene in patients with Type II DM and dementia and to explore the correlation between GDNF expression and cognitive function.
Methods: Blood samples were collected from 88 diabetic patients with dementia and 12 healthy controls. GDNF serum levels were measured using Chemiluminescent Immunoassay (CLIA), and genomic DNA was isolated for expression analysis via RT-qPCR. Cognitive function was evaluated using the Mini Mental State Examination (MMSE). Statistical analysis, including t-tests and one-way ANOVA, was performed using Graphpad Prism version 9.0.
Results: Diabetic dementia patients exhibited significantly lower GDNF serum levels (4.37±1.38 µg/mL) compared to healthy controls (11.37±3.64 µg/mL, p=0.014). MMSE scores were also lower in the patient group (12.26±4.56) than in controls (24.1±3.12, p=0.009). RT-qPCR results showed a relative fold decrease in GDNF expression of 4.1 in dementia patients, indicating underexpression of the GDNF gene.1
Conclusion: The reduced expression of GDNF in patients with Type II DM and dementia underscores its potential as a biomarker for cognitive impairment. These findings pave the way for further research into GDNF-targeted therapies, which could prove pivotal in early detection and management of dementia in diabetic populations.
Downloads
References
Saedi E, Gheini MR, Faiz F, Arami MA. Diabetes mellitus and cognitive impairments. World J Diabetes. 2016;7(17):412–22.
Quan M, Cao S, Wang Q, Wang S, Jia J. Genetic Phenotypes of Alzheimer's Disease: Mechanisms and Potential Therapy. Phenomics (Cham). 2023;3(4):333–49.
Islam S, Sun Y, Gao Y, Nakamura T, Noorani AA, Li T, Wong PC, Kimura N, Matsubara E, Kasuga K, Ikeuchi T, Tomita T, Zou K, Michikawa M. Presenilin Is Essential for ApoE Secretion, a Novel Role of Presenilin Involved in Alzheimer's Disease Pathogenesis. J Neurosci. 2022;42(8):1574–86.
Ochalek A, Mihalik B, Avci HX, Chandrasekaran A, Téglási A, Bock I, Giudice ML, Táncos Z, Molnár K, László L, Nielsen JE, Holst B, Freude K, Hyttel P, Kobolák J, Dinnyés A. Neurons derived from sporadic Alzheimer's disease iPSCs reveal elevated TAU hyperphosphorylation, increased amyloid levels, and GSK3B activation. Alzheimer's Res Ther. 2017;9(1):90.
Quan M, Cao S, Wang Q, Wang S, Jia J. Genetic Phenotypes of Alzheimer's Disease: Mechanisms and Potential Therapy. Phenomics (Cham). 2023;3(4):333–49.
Samario-Román J, Larqué C, Pánico P, Ortiz-Huidobro RI, Velasco M, Escalona R, Hiriart M. GDNF and Its Role in Immunoendocrine Communication during Metabolic Syndrome. Int J Mol Sci. 2023;24(3):1957.
Hölscher C. Insulin Signaling Impairment in the Brain as a Risk Factor in Alzheimer's Disease. Front Aging Neurosci. 2019;11:88.
Abubakar MB, Sanusi KO, Ugusman A, Mohamed W, Kamal H, Ibrahim NH, Khoo CS, Kumar J. Alzheimer's Disease: An Update and Insights Into Pathophysiology. Front Aging Neurosci. 2022;14:742408.
Do Carmo S, Kannel B, Cuello AC. The Nerve Growth Factor Metabolic Pathway Dysregulation as Cause of Alzheimer's Cholinergic Atrophy. Cells. 2021;11(1):16.
Pentz R, Iulita MF, Ducatenzeiler A, Bennett DA, Cuello AC. The human brain GDNF metabolic pathway is impaired in the pre-clinical and clinical continuum of Alzheimers disease. Mol Psychiatry. 2021;26(10):6023–37.
Abubakar MB, Sanusi KO, Ugusman A, Mohamed W, Kamal H, Ibrahim NH, Khoo CS, Kumar J. Alzheimer's Disease: An Update and Insights Into Pathophysiology. Front Aging Neurosci. 2022;14:742408.
Barloese MCJ, Bauer C, Petersen ET, Hansen CS, Madsbad S, Siebner HR. Neurovascular Coupling in Type 2 Diabetes With Cognitive Decline. A Narrative Review of Neuroimaging Findings and Their Pathophysiological Implications. Front Endocrinol (Lausanne). 2022;13:874007.
Spinelli M, Fusco S, Grassi C. Brain Insulin Resistance and Hippocampal Plasticity: Mechanisms and Biomarkers of Cognitive Decline. Front Neurosci. 2019;13:788.
Sherwani SI, Khan HA, Ekhzaimy A, Masood A, Sakharkar MK. Significance of HbA1c Test in Diagnosis and Prognosis of Diabetic Patients. Biomark Insights. 2016;11:95–104.
Rajmohan R, Reddy PH. Amyloid-Beta and Phosphorylated Tau Accumulations Cause Abnormalities at Synapses of Alzheimer's disease Neurons. J Alzheimers Dis. 2017;57(4):975–99.
Rajmohan R, Reddy PH. Amyloid-Beta and Phosphorylated Tau Accumulations Cause Abnormalities at Synapses of Alzheimer's disease Neurons. J Alzheimers Dis. 2017;57(4):975–99.
Gerke N, Hellberg A, Eppendorf AG. Straightforward PCR optimization and highly flexible operation on the dual block thermocycler Mastercycler® nexus GX2. Eppendorf Application Note 289; 2013.
Bruno F, Abondio P, Montesanto A, Luiselli D, Bruni AC, Maletta R. The Nerve Growth Factor Receptor (GDNFR/p75NTR): A Major Player in Alzheimer's Disease. Int J Mol Sci. 2023;24(4):3200.
Shen LL, Li WW, Xu YL, Gao SH, Xu MY, Bu XL, Liu YH, Wang J, Zhu J, Zeng F, Yao XQ, Gao CY, Xu ZQ, Zhou XF, Wang YJ. Neurotrophin receptor p75 mediates amyloid β-induced tau pathology. Neurobiol Dis. 2019;132:104567.
Bradshaw RA, Pundavela J, Biarc J, Chalkley RJ, Burlingame AL, Hondermarck H. GDNF and ProGDNF: Regulation of neuronal and neoplastic responses through receptor signaling. Adv Biol Regul. 2015;58:16–27.
Dedoni S, Olianas MC, Ingianni A, Onali P. Type I interferons up-regulate the expression and signalling of p75 NTR/TrkA receptor complex in differentiated human SH-SY5Y neuroblastoma cells. Neuropharmacology. 2014;79:321–34.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Murad Ahmad, Zoreen Shafaq, Ali Raza Rajput, Rabia Bughio
This work is licensed under a Creative Commons Attribution 4.0 International License.