Keck School Faculty

Mariangela Nikolakopoulou, PhD
Mariangela Nikolakopoulou, PhD
Assistant Professor of Research Physiology & Biophysics
Zilkha Neurogenetic Institute
ZNI 301,1501 San Pablo Street Health Sciences Campus Los Angeles
I’m particularly interested in research associated with neurodegenerative diseases Early in my scientific career, I focused my research on Multiple Sclerosis and I used in vitro models to investigate factors that may enhance neurogenesis in white matter lesions. I discovered through my studies that trypsinogen, a serine protease, is an activated-microglia secreted factor that increases neurogenesis. Later in my career I applied my previous findings to discover neuroprotective agents against toxicity in Alzheimer Disease.
Currently, my studies focus on blood brain barrier (BBB) damage and vascular-related neurodegeneration. In particular, I am studying pericyte deficiency in relation to demyelination, while my recent studies focus on selective ablation of pericytes in adulthood causing BBB leakage and distortion of capillary density. In addition, I am studying the effects of endothelial LRP1 depletion and am showing that short and long-term treatment with Cyclosporine A can reverse BBB leakage and neurodegeneration respectively.
Over the years I have been successful in obtaining extramural funding from the Multiple Sclerosis society (NMMS) to study the effects of astrocytic ephrinB1 in demyelination and remyelination.
Some of the techniques I apply for my studies include cell culture, western blotting, immunoprecipitation, flow cytometry, immunohistochemistry/immunofluorescence, immunocytochemistry, electron microscopy pre-embedding immunohistochemistry, cell transfection, viral infections, intracranial injections, microvessel isolation, CSF extraction, and reverse transcriptase chain polymerase reaction.

Pericyte loss leads to circulatory failure and pleiotrophin depletion causing neuron loss Nat Neurosci. 2019 07; 22(7):1089-1098. . View in PubMed

3K3A-activated protein C blocks amyloidogenic BACE1 pathway and improves functional outcome in mice J Exp Med. 2019 02 04; 216(2):279-293. . View in PubMed

Pericyte degeneration causes white matter dysfunction in the mouse central nervous system Nat Med. 2018 03; 24(3):326-337. . View in PubMed

Functional Consequences of Synapse Remodeling Following Astrocyte-Specific Regulation of Ephrin-B1 in the Adult Hippocampus J Neurosci. 2018 06 20; 38(25):5710-5726. . View in PubMed

Role of Neuropilin-1/Semaphorin-3A signaling in the functional and morphological integrity of the cochlea PLoS Genet. 2017 Oct; 13(10):e1007048. . View in PubMed

Regional early and progressive loss of brain pericytes but not vascular smooth muscle cells in adult mice with disrupted platelet-derived growth factor receptor-ß signaling PLoS One. 2017; 12(4):e0176225. . View in PubMed

Presenilin 1 promotes trypsin-induced neuroprotection via the PAR2/ERK signaling pathwayEffects of presenilin 1 FAD mutations. Neurobiol Aging. 2016 06; 42:41-9. . View in PubMed

Astrocytic Ephrin-B1 Regulates Synapse Remodeling Following Traumatic Brain Injury ASN Neuro. 2016 Jan-Feb; 8(1):1-18. . View in PubMed

Activated microglia enhance neurogenesis via trypsinogen secretion Proc Natl Acad Sci U S A. 2013 May 21; 110(21):8714-9. . View in PubMed

Synaptic maturation of the Xenopus retinotectal system: effects of brain-derived neurotrophic factor on synapse ultrastructure J Comp Neurol. 2010 Apr 01; 518(7):972-89. . View in PubMed

Netrin participates in the development of retinotectal synaptic connectivity by modulating axon arborization and synapse formation in the developing brain J Neurosci. 2009 Sep 09; 29(36):11065-77. . View in PubMed

Cell-autonomous TrkB signaling in presynaptic retinal ganglion cells mediates axon arbor growth and synapse maturation during the establishment of retinotectal synaptic connectivity J Neurosci. 2007 Mar 07; 27(10):2444-56. . View in PubMed

Passive avoidance training is correlated with decreased cell proliferation in the chick hippocampus Eur J Neurosci. 2006 Nov; 24(9):2631-42. . View in PubMed

Early post-hatching sex differences in cell proliferation and survival in the quail telencephalic ventricular zone and intermediate medial mesopallium Brain Res Bull. 2006 Jun 30; 70(2):107-16. . View in PubMed

Passive avoidance training decreases synapse density in the hippocampus of the domestic chick Eur J Neurosci. 2006 Feb; 23(4):1054-62. . View in PubMed

BDNF stabilizes synapses and maintains the structural complexity of optic axons in vivo Development. 2005 Oct; 132(19):4285-98. . View in PubMed

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