The role of folic acid supplementation has proven to be extremely effective in preventing the occurrence of neural tube defects and other congenital abnormalities in humans. Because this suggests that folic acid can modulate or enhance key mechanisms for growth and differentiation in the CNS, our laboratory has been instrumental in hypothesizing and proving a significant role for folic acid in regeneration and repair of the adult CNS after injury. As part of an effort to study the mechanism of such a pro-regenerative response, we have shown that folate-mediated CNS regeneration depends on injury-related induction of folate receptor FOLR1 expression, intact intracellular folate activation, and a functional methylation cycle. The effect of folate on the regeneration of afferent spinal neurons is biphasic and dose-dependent, and correlates closely over its dose range with global and gene-specific DNA methylation, and with expression of both the folate receptor FOLR1 as well as the de novoDNA methyltransferases. As such, we hypothesize an epigenetic mechanism in CNS repair, and through our current laboratory efforts, we seek to understand the underpinnings of this mechanism and its implications. This work provides possible avenues for new pharmacologic approaches to treating brain and spinal cord injuries.
Principal Investigator: Bermans J. Iskandar, MD
Lab Manager: Nithya Hariharan, MD
Undergrads and med students:
Bridget Barnes, Samantha Ryan, Felissa Hong, Victor Wakim, Alyssa Thalacker, Tenzin Kunsel,
Kyle Zielinski, Elvis Vidal, Sarah Langer, David Chen, Sara Sayyahmelli, Joyce Koueik, Albert Hu,
Laura Borth, Alex Jedrzejczak, Joe Cessare, Alaa Khatib
- March of Dimes Foundation grant (ongoing)
- NIH 1R01HD047516-01 (2006-2011)
- NIH 3R01HD047516-04S1 ARRA Supplement (2011-2012)
- American Chiari and Syringomyelia Alliance Project: Multi-Center Chiari /Syringomyelia Clinical Trial (ongoing)
- Theodore Batterman Family Foundation grant (ongoing)
- Iskandar BJ, Resnick DK, Nelson A, Skene JHP, Gao P, Johnson C, Hariharan N: Folic acid supplementation enhances repair mechanism of the adult CNS Ann Neurol. 2004 Aug;56(2):221-7.
- Bomze H, Bulsara K, Iskandar B, Caroni P, Pate Skene J. Spinal axon regeneration evoked by replacing two growth cone proteins in adult neurons. Nature Neuroscience [serial online]. January 2001;4(1):38. Available from: Academic Search Premier, Ipswich, MA. Accessed August 25, 2010.
- Bermans J. Iskandar, Elias Rizk, Brenton Meier, Nithya Hariharan, Teodoro Bottiglieri, Richard H. Finnell, David F. Jarrard, Ruma V. Banerjee, J.H. Pate Skene, Aaron Nelson, Folate regulation of axonal regeneration in the rodent central nervous system through DNA methylation, Journal of Clinical Investigation, 2010.
Office: (608) 263-9651
Lab: (608) 262-6080
Department of Neurological Surgery
Box 8660 Clinical Science Center – K4
600 Highland Ave Madison, WI 53792