BUKU ABSTRAK - Universiti Putra Malaysia

Health
Keywords: Microglia, tocotrienol
Microglia are the resident macrophages of the central nervous system (CNS). In the normal CNS, they are
in a resting condition, characterised by low expression of MHC class II (MHC II) and costimulatory molecules
such as CD40. Following activation by various stressors, microglia acquires an inflammatory phenotype and
the continuous activation of microglia is thought to exacerbate neuronal damage. It is also believed that with
increasing age, the inflammatory response of microglia becomes uncontrolled. In this study, the effects of age on
microglia responses were determined by culturing microglia from Sprague Dawley rats of six days, 2-4 months
and three years old. Microglia were then activated with lipopolysaccharide (LPS) or beta amyloid (A?) and
assessed for nitric oxide (NO) production, proliferative capacity and expression of activation markers, at different
time points. Griess assay and the tritiated thymidine proliferation assay were performed to assess NO production
and microglia proliferation respectively. It was observed that at 48 hours, NO production and proliferation rate
ware higher in neonatal microglia compared to adult. Expression of activation markers MHC II and CD40 was
determined by immunophenotyping. Even under resting condition, it was observed that neonatal and adult
microglia have CD40 expression; however this expression was higher in adult microglia compared to neonatal.
Similarly, after activation with LPS and A?, CD40 expression was still higher in adult cells compared to neonatal.
In addition, MHC II expression was also observed to be higher in adult cells in resting and after activation with
LPS and A?. This shows that adult microglia have stronger costimulatory signals which indicate its potential for
subsequent activation of T cells that can exacerbate inflammation. Thus, as a result of our work, we demonstrate
different responses between primary cells of neonatal and adult microglia to LPS and A? stimulation.
Keywords: Microglia, aging, immunosenescence
Potential Anti-inflammatory Properties of Tocotrienols on Microglia
Dr. Sharmili Vidyadaran
Shi Wei Tan and Maha Abdullah
Faculty of Medicine and Health Sciences, University Putra Malaysia,
43400 UPM Serdang, Selangor, Malaysia.
+603-8947 2376; sharmili@medic.upm.edu.my
Microglia are the tissue-specific macrophages of the central nervous system (CNS). In response to various
stimuli, they transform into functioning phagocytic cells, proliferate and produce a wide array of mediators
to promote inflammation. However, chronic inflammatory responses of microglia can lead to neuronal death
and is implicated in various neurodegenerative diseases. Studies have demonstrated that vitamin E is able to
attenuate the production of inflammatory mediators in various cell types. In neurones, tocopherol fractions of
vitamin E are protective by reducing lipopolysaccharide (LPS)-induced peroxide radical and nitric oxide (NO)
radicals by activated microglia. Tocotrienol fractions are also potently anti-inflammatory and are less studied on
microglia cells. The aim of this project is to determine the potential anti-inflammatory properties of tocotrienols
on the BV2 microglia cell line. Cells were treated with?-tocotrienol,?-tocotrienol, ?-tocotrienol or Tocomin?50%
to determine their effects on nitric oxide (NO) production, proliferation rate and phagocytic rate of microglia
following activation by lipopolysaccharide (LPS). Tocotrienol fractions and Tocomin?50% were first screened
for potential anti-inflammatory activities via a NO assay. Five different concentrations of tocotrienols - 100nM,
250nM, 2.5?M, 10?M and 50?M were tested. We found ?-tocotrienol to be most effective at reducing NO levels,
up to 76% (p