HYBRID EVENT: You can participate in person at Orlando, USA or Virtually from your home or work.

6th Edition of International Conference on Neurology and Brain Disorders

October 24 -26, 2022

October 24 -26, 2022 | Orlando, Florida, USA
INBC 2022

Kuljira Mongkolpobsin

Speaker at Neurology and Brain Disorders 2022 - Kuljira Mongkolpobsin
Chulalongkorn University, Thailand
Title : Azadirachta indica A. Juss. extracts Inhibits Glutamate-Induced Neuronal Apoptosis through Attenuation of Mitochondrial Dysfunction and ERK/p38 MAPK-CHOP Signaling Pathways in HT-22 Cells

Abstract:

Neurodegenerative diseases (NDs) are the age-related diseases which represent a major cause of mortality in aging population nowadays. Previous studies have shown that glutamate, the most abundant excitatory neurotransmitter, significantly increases in extracellular fluid of the patient’s brain and is the cause of neurodegeneration in NDs. High level of extracellular glutamate depletes glutathione production leading to reactive oxygen species (ROS) accumulation. Increased ROS induces the oxidative damage to mitochondrial components, the main source of ROS production, causing mitochondrial dysfunction which is removed by mitophagy pathway. However, continuous degradation of damaged mitochondria induces cells to stress condition and undergoes apoptosis. Meanwhile, the elevated glutamate activates calcium (Ca2+)-permeable ion channels increasing Ca2+ influx into cells. Subsequently, Ca2+ overload induces mitogen-activated protein kinase (MAPK) signaling pathway (extracellular signal–regulated kinase (ERK) and p38) phosphorylation followed by C/EBP Homologous Protein (CHOP) activation which is an apoptosis-related transcription factor which further induces neuronal apoptosis.

Azadirachta indica A. Juss. (AI), commonly known as neem, is a traditional herb which has long been recognized for its therapeutic effects such as anti-cancer, antidiabetic and anti-inflammatory activities. However, little is known about the effect of AI flowers on neuroprotection. This work was aimed at studying the effect and underlying mechanisms of AI flowers, extracted using hexane (AIH) and dichloromethane (AID), on inhibiting glutamate-induced neuronal apoptosis in mouse hippocampal neurons (HT-22 cells). We found that co-treatment with AIH or AID, and glutamate significantly inhibited glutamate-induced neuronal apoptosis in HT-22 cells. For their underlying mechanisms, AIH and AID significantly reduced ROS accumulation, ameliorated mitochondrial dysfunction through recovering ATP production and mitochondrial membrane potential, and attenuated mitophagy overactivation through inactivating autophagic proteins (LC3 and p62) and decreasing mitochondria and LC3 colocalization. Meanwhile, glutamate treatment also increased Ca2+ influx followed by MAPK (ERK and p38) and CHOP activation which induce neuronal apoptosis. However, AIH and AID significantly reversed these changes. In addition, we also analyzed phytochemical constituents of AIH and AID by GC-MS. We found that AIH or AID contained β-vatirenene, Oleic acid and Stigmasterol which has been reported for their antioxidant and anti-inflammation activities.

All these results suggest that AI flowers have neuroprotective effect against glutamate-induced neuronal cell death, thus further investigations should be carried out for potential neuroprotectants.

What will audience learn from your presentation?

  • In this presentation, the audience will understand about the mechanism on glutamate-induced neurotoxicity in NDs and also know about the underlying mechanisms of Azadirachta indica A. Juss. (AI) flowers on inhibiting glutamate-induced neuronal apoptosis through ameliorating mitochondrial dysfunction and downregulating MAPK-CHOP signaling pathway.
  • Since AI flowers are a commonly edible herb in tropical countries and the study shows that AI flowers have neuroprotective effect against glutamate-induced neurotoxicity, it’d be beneficial to the elders who have the high risk for NDs.
  • In this presentation, we discussed the neuroprotective effect of AI flowers on mouse hippocampal cell line and it needs to be further investigated for serving as a neuroprotective drug, hence this study should be useful for those who are interested in drug development of NDs.

 

Biography:

Ms. Kuljira Mongkolpobsin studied bachelor's degree in the field of Medical Technology, Faculty of Allied Health Sciences, Chulalongkorn University, Thailand. Now, she is a Ph.D. candidate in the field of Clinical Biochemistry and Molecular Medicine, Department of Clinical Chemistry at the same faculty.

Watsapp