Professor, Psychiatry & Behavioural Neurosciences
Associate Member, Biology
Associate Member, MOBIX
B.Sc., Stanford University; Ph.D., University of California at Berkeley
Phone: 905-525-9140 ext. 23344
Regulation of neurotrophic factors and their precursors. Role and regulation of NGF and BDNF in Alzheimer’s disease, epilepsy, and autism. Peripheral nerve injury.
Dr. Fahnestock's laboratory uses molecular techniques to study proteins essential for nervous system development, plasticity and function. Her research interests centre on the regulation and biosynthesis of neurotrophic factors and their involvement in neurodegenerative diseases. Neurotrophic factors such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are necessary for peripheral and central nervous system development, maintenance and response to injury. The levels of these factors are tightly controlled in a tissue-specific manner. Their biological activity is regulated by a number of processes including transcriptional regulation, proteolytic processing of precursors, and binding to inhibitors and receptors. Her laboratory is attempting to dissect the mechanisms that regulate NGF and BDNF biosynthesis using both rodent and human experimental systems, with a particular focus on human CNS conditions such as Alzheimer's disease.
- Molecular analysis of BDNF promoter elements and signal transduction pathways controlling expression in Alzheimer's disease using human brain, transgenic mice and neuronal cell culture
- Characterization of proNGF protein expression, biological activity and transport in normal brain and in Alzheimer's disease using cell culture
- BDNF expression, post-translational modifications and signal transduction in autism
- Role of neurotrophic factors and mechanisms of electrical stimulation and sensory protection of muscle following peripheral nerve injury
- Garcia K.L.P., Yu G., Nicolini C., Michalski B., Garzon D., Chiu V. S., Tongiorgi E., Szatmari P., and Fahnestock M. Altered balance of proteolytic forms of pro-brain-derived neurotrophic factor in autism. J. Neuropathol. Exp. Neurol. 71(4), 289-297 (2012).
- Francis B. M., Yang J., Hajderi E., Brown M. E., Michalski B., McLaurin J., Fahnestock M., and Mount H. T.J. Reduced tissue levels of noradrenaline are associated with behavioral phenotypes of the TgCRND8 mouse model of Alzheimer’s disease. Neuropsychopharmacology 37(8), 1934-1944 (2012).
- Fahnestock M., Marchese M., Head E., Pop V., Michalski B., Milgram W. N., and Cotman C. W. BDNF increases with behavioural enrichment and an antioxidant diet in the aged dog. Neurobiol. of Aging 33, 546–554 (2012).
- Francis B. M., Kim J., Barakat M. E., Fraenkl S., Yucel Y. H., Peng S., Michalski B., Fahnestock M., McLaurin J. and Mount H.T.J. Object recognition memory and BDNF expression are reduced in young TgCRND8 mice. Neurobiol, of Aging 33(3):555-63 (2012).
- Fahnestock, M. BDNF: The link between beta-amyloid and memory loss. Future Neurology, 6(5), 627-639 (2011).
- Willand MP, Lopez JP, de Bruin H, Fahnestock M, Holmes M, Bain JR. A new system and paradigm for chronic stimulation of denervated rat muscle. J. Biomedical Engineering, 31, 87-92 (2011).
- Kawaja MD, Smithson LJ, Elliott J, Trinh G, Crotty AM, Michalski B, Fahnestock M. Nerve growth factor promoter activity revealed in mice expressing enhanced green fluorescent protein. J. Comp. Neurol., 519, 2522-2545 (2011).
- Perez SE, Bin H, Muhammad N, Kwang Oh, Fahnestock M, Ikonomovic m, and Mufson EJ. Cholinotrophic basal forebrain system alterations in 3xTg-AD transgenic mice. Neurobiol. of Disease 41, 338–352 (2011).
- Elsohemy A,Butler R, Bain JR, and Fahnestock M. Sensory protection of the muscle spindle following peripheral nerve injury. Plastic Reconstr. Surgery 124, 1860-1868 (2009).
- Peng S, Garzon DJ, Marchese M, Klein W, Ginsberg SD, Francis B, Mount HTJ, Mufson EJ, Salehi A and Fahnestock M. Decreased brain-derived neurotrophic factor depends upon Aβ aggregation state in transgenic mouse models of Alzheimer’s disease. J. Neurosci. 29, 9321–9329 (2009). Reported in news article by Pat McCaffrey at www.Alzforum.org.
- Masoudi R, Ioannou MS, Coughlin MD, Pagadala P, Neet KE, Clewes O, Allen SJ, Dawbarn D, and Fahnestock M. Biological activity of nerve growth factor precursor is dependent upon relative levels of TrkA and p75NTR receptors. J. Biol. Chem. 284, 18424–18433 (2009).
- Michalski B, Bain JR, and Fahnestock M. Long-term changes in neurotrophic factor expression in distal nerve stump following denervation and reinnervation with motor or sensory nerve. J. Neurochem. 105, 1244-1252 (2008).
- Garzon DJ & Fahnestock M. Oligometric amyloid decreases basal levels of brain-derived neurotrophic factor (BDNF) mRNA via specific downregulation of BDNF transcripts IV and V in differentiated human neuroblastoma cells. Journal of Neuroscience, 2007; 27(1): 2628-2635.
- Buttigieg H, Kawaja MD & Fahnestock M. Neurotrophic activity of proNGF in vivo. Experiemental Neurology, 2006; Dec 20.
- Batt J, Bain J, Goncalves J, Michalski B, Plant P, Fahnestock M & Woodgett J. Differential gene expression profiling of short and long term denervated muscle. FASEB Journal , 2006; 20(1):115-117.
- Peng S, Wuu J, Mufson EJ & Fahnestock M. Precursor form of brain-derived neurotroophic factor and mature brain-derived neurotrophic factor are decreased in the pre-clinical stages of Alzheimer's disease. Journal of Neurochemistry, 2005; 93(6); 1412-1421.
- Veltri K, Kwiecien JM, Minet W, Fahnestock M & Bain JR. Contribution of the distal nerve sheath to nerve and muscle preservation following denervation and sensory protein. Journal of Reconstructive Microsurgery, 2005; 1:57-70.
- Fahnestock M, Yu G, Michalski B, Mathew S, Colquhoun A, Ross GM & Coughlin MD. The nerve growth factor precursor proNGF exhibits neurotrophic activity but is less active than mature nerve growth factor. Journal of Neurochemistry, 2004; 89(3): 581-592.
- Xu B, Michalski B, Racne RJ & Fahnestock M. The effects of brain-derived neurotrophic factor (BDNF) administration on kindling induction, Trk expression and seizure-related morphological changes. Neuroscience, 2004; 126:521-531.
- Zhao C, Veltri K, Li S, Bain JR & Fahnestock M. NGF, BDNF, NT-3 and GDNF mRNA expression in rat skeletal muscle following denervation and sensory protection. Journal of Neurotrauma, 2004; 21:1468-1478.
- Morimoto K, Fahnestock M & Racine RJ. Kindling and status epilepticus models of epilepsy: Rewiring the brain. Progress in Neurobiology, 2004; 73:1-60.
- Peng S, Wuu J, Mufson EJ & Fahnestock M. Increased proNGF levels In subjects with mild cognitive impairment and mild Alzheimer’s Disease. Journal of Neuropathology and Experimental Neurology, 2004; 63: 641-649.
- Michalski B & Fahnestock M.. Pro-brain-derived neurotrophic factor is decreased in parietal cortex in Alzheimer's disease. Molecular Brain Research, 2003; 111: 148-154.
- Xu B, Li S, Brown A, Gerlai R, Fahnestock M & Racine RJ. EphA/EphrinA interactions regulate epileptogenesis and activity-dependent axonal sprouting in adult rats. Molecular and Cellular Neurosciences, 2003; 24: 984-999..
- Fahnestock M, Yu G & Coughlin MD. ProNGF: A neurotrophic or an apoptotic molecule? In: T. Merryweather (ed.), Progress in Brain Research, Vol. 146, NGF and Related Molecules in Health and Disease. Elsevier Science, Amsterdam, 2003; pp. 101-110.
- Garzon D, Yu G & Fahnestock M. A new BDNF transcript and decrease in BDNF transcripts 1, 2 and 3 in Alzheimer's disease parietal cortex. Journal of Neurochemistry, 2002; 82: 1058-1064 .
- Fahnestock M, Garzon D, Holsinger RMD & Michalski B. Neurotrophic factors and Alzheimer's disease: Are we focusing on the wrong molecule? Journal of Neural Transmission, 2002;. [Suppl.] 62: 241-252.