Future Directions
The study performed by Distler (et al, 2012, see primary literature review page) Glo1 overexpression increases anxiety-like behavior. It also proved that increasing methylglyoxal (MG) in the brain directly decreased anxiety.
How does this advance studies in anxiety treatment?
Increasing MG in the brain
Manuka honey, or tea tree honey, has been used as a natural antibacterial, anti-fungal, and anti-inflammatory product in holistic medicine and cosmetics. Its unique benefits have piqued the interest of many researchers, leading to a discovery in 2008 by Professor Thomas Henle of University of Dresden that it was methylglyoxal (MG) that gives Manuka honey its antibacterial properties [1]. In the same way that MG curbs rapid bacterial cell growth, it also suppresses cancerous tumor growth [2].
It is possible that methylglyoxal levels are increased in the brain by adding Manuka honey into the diet. This has not been investigated, and may be a natural approach to decreasing anxiety.
It is possible that methylglyoxal levels are increased in the brain by adding Manuka honey into the diet. This has not been investigated, and may be a natural approach to decreasing anxiety.
Proposed Experiment
Question: How does addition of Manuka honey to the diet impact the activity of GLO1?
Hypothesis: GLO1 activity will remain constant, while MG is allowed to accumulate in the brain.
Experimental Outline:
Hypothesis: GLO1 activity will remain constant, while MG is allowed to accumulate in the brain.
Experimental Outline:
- Using Bacterial Artificial Chromosome, create transgenic mice with identical copies of GLO1 gene
- Randomizing mice into two groups
- For 30 days, feed group one a diet including Manuka honey and group two a normal diet
- Perform a 2D gel analysis of protein expression in the brain of both groups and observe any differences in GLO1
- Quantify GLO1 using MALDI-TOF mass spectrometry and observe any difference in GLO1
Additional Directions and Points of Interest
Manuka honey and MG Concentrations
Does a diet of Manuka honey increase MG concentrations in the brain? Does a diet of Manuka honey decrease anxious behavior?
Both could be observed through the above experimental procedure. Behavior can be measured by open field tests, and MG can be quantified by HPLC.
Both could be observed through the above experimental procedure. Behavior can be measured by open field tests, and MG can be quantified by HPLC.
Inhibiting GLO1
Does inhibition of GLO1 decrease anxiety?
Inhibiting the function of GLO1 could allow for MG to accumulate in the brain. Several chemical inhibitors of GLO1 have recently been discovered [3]. GLO1 can also be genetically inhibited by RNAi silencing.
Inhibiting the function of GLO1 could allow for MG to accumulate in the brain. Several chemical inhibitors of GLO1 have recently been discovered [3]. GLO1 can also be genetically inhibited by RNAi silencing.
Protein Network of GLO1
Are other proteins functioning with GLO1 that change anxious behavior?
2D gel analysis could reveal any changes in activity other proteins in the GLO1 protein network when GLO1 activity itself is changed. Other proteins might be impacting anxiolytic behavior in addition to GLO1.
2D gel analysis could reveal any changes in activity other proteins in the GLO1 protein network when GLO1 activity itself is changed. Other proteins might be impacting anxiolytic behavior in addition to GLO1.
Download powerpoint presentation of findings and proposed research
References
[1] "Methylglyoxal and the Health Benefits of Tea Tree (Manuka) Honey."Chefshop.com. N.p., n.d. Web. 18 Apr. 2013.
[2] Intravenous administration of manuka honey inhibits tumor growth and improves host survival when used in combination with chemotherapy in a melanoma mouse model. Fernandez-Cabezudo MJ, El-Kharrag R, Torab F, Bashir G, George JA, El-Taji H, al-Ramadi BK.
PLoS One. 2013;8(2):e55993. doi: 10.1371/journal.pone.0055993. Epub 2013 Feb 7.
[3] Al-Balas Q, Hassan M, Al-Oudat B, Alzoubi H, Mhaidat N, Almaaytah A. Generation of the First Structure-Based Pharmacophore Model Containing a Selective “Zinc Binding Group” Feature to Identify Potential Glyoxalase-1 Inhibitors. Molecules. 2012; 17(12):13740-13758.
[4] Identification and quantification of methylglyoxal as the dominant antibacterial constituent of Manuka (Leptospermum scoparium) honeys from New Zealand. Mavric E, Wittmann S, Barth G, Henle T.Mol Nutr Food Res. 2008 Apr; 52(4):483-9.
[5] Manuka honey inhibits cell division in methicillin-resistant Staphylococcus aureus. Jenkins R, Burton N, Cooper R. J Antimicrob Chemother. 2011 Nov; 66(11):2536-42. Epub 2011 Sep 7.
[2] Intravenous administration of manuka honey inhibits tumor growth and improves host survival when used in combination with chemotherapy in a melanoma mouse model. Fernandez-Cabezudo MJ, El-Kharrag R, Torab F, Bashir G, George JA, El-Taji H, al-Ramadi BK.
PLoS One. 2013;8(2):e55993. doi: 10.1371/journal.pone.0055993. Epub 2013 Feb 7.
[3] Al-Balas Q, Hassan M, Al-Oudat B, Alzoubi H, Mhaidat N, Almaaytah A. Generation of the First Structure-Based Pharmacophore Model Containing a Selective “Zinc Binding Group” Feature to Identify Potential Glyoxalase-1 Inhibitors. Molecules. 2012; 17(12):13740-13758.
[4] Identification and quantification of methylglyoxal as the dominant antibacterial constituent of Manuka (Leptospermum scoparium) honeys from New Zealand. Mavric E, Wittmann S, Barth G, Henle T.Mol Nutr Food Res. 2008 Apr; 52(4):483-9.
[5] Manuka honey inhibits cell division in methicillin-resistant Staphylococcus aureus. Jenkins R, Burton N, Cooper R. J Antimicrob Chemother. 2011 Nov; 66(11):2536-42. Epub 2011 Sep 7.
Site created by: Emma Baar
Last updated: 5-14-2013
University of Wisconsin - Madison
Last updated: 5-14-2013
University of Wisconsin - Madison