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Jenny Libien, MD PhD
Department of Pathology, Division of Neuropathology
Office location: BSB 4-27
Tel: (718) 270-6304
Fax: (718) 270-3313
Lab: (718) 270-8970
Retinoids and retinoid transport proteins in the central nervous system
Retinoids (vitamin A and its analogs) are involved in multiple processes in the adult brain, including adult neurogenesis, memory formation, and cortical synchrony during sleep. Retinoid deficiency has been reported to result in decreased long-term potentiation (LTP), long-term depression (LTD) and decreased hippocampal dependent learning. Retinoid toxicity has been associated with intracranial hypertension and with impaired adult neurogenesis. Our work consists of the following aims:
1. To determine the role of retinoids in the adult central nervous system using the LRAT (lecithin:retinol acyltransferase) knockout mouse, which lacks significant retinoid stores.
2. To elucidate the processes responsible for retinoid delivery to human and mouse brain and how the brain maintains the retinoid sufficiency that is essential for normal function.
3. To investigate the role of retinoid signaling in the new neurons of the dentate gyrus.
Retinoid signaling in the dentate gyrus. Immunohistochemical stain for beta-galactosidase (red) in the RARb2-beta galactosidase transgenic mouse reflects the presence of retinoic acid in the hippocampus. Beta-galactosidase expression is present in a subset of granular neurons of the dentate gyrus.
Adult neurogenesis during aging and neurodegeneration
Neural stem cells are present in adult animals, including humans, in two regions, the subgranular zone of the hippocampal dentate gyrus and the subventricular zone. From animal studies, the new neurons of the hippocampal dentate gyrus have been proposed to be involved in the regulation of mood and to play a role in the formation of certain types of memory. Adult hippocampal stem cells have been suggested as therapeutic targets to improve memory in Alzheimer’s disease and to treat depression, however little is known about adult neurogenesis in humans. Our laboratory is investigating neurogenesis in the dentate gyrus during human aging and neurodegeneration. This work is being funded by a Dean’s Research Initiative grant and consists of the following aims:
1. To determine whether neurogenesis decreases with age and if the decrease is roughly linear or whether there are times of rapid change.
2. To explore the relationship between neurogenesis and neuronal injury in different neurodegenerative diseases such as Alzheimer’s disease and in Dementia with Lewy bodies
Selected Recent Publications
Libien J and Blaner WS, Retinol and Retinol-Binding Protein in Cerebrospinal Fluid: Can vitamin A take the “Idiopathic” out of Idiopathic Intracranial Hypertension? Journal of Neuro-Ophthalmol. 27: 253-257, 2007.
Nirenberg M, Libien J, Vonsattel JP, Fahn S, Multiple System Atrophy in a Patient with the Spinocerebellar Ataxia 3 Gene Mutation. Movement Disorders, 22(2): 251-254, 2007.
O'byrne SM, Wongsiriroj N, Libien JM, Vogel S, Goldberg IJ, Baehr W, Palczewski K, Blaner WS. Retinoid absorption and storage is impaired in mice lacking lecithin: Retinol acyltransferase (LRAT). J Biol Chem. 280(42): 35647-35657, 2005.
Libien J, Sacktor TC, Kass IS. Magnesium blocks the loss of protein kinase C, leads to a transient translocation of PKCa and PKCe, and improves recovery after anoxia in rat hippocampal slices. Brain Res Mol Brain Res.136(1-2):104-111, 2005.
Hernandez AI, Blace N, Crary JF, Serrano PA, Leitges M, Libien JM, Weinstein G, Tcherapanov A, Sacktor TC. Protein kinase M zeta synthesis from a brain mRNA encoding an independent protein kinase C zeta catalytic domain. Implications for the molecular mechanism of memory. J. Biol. Chem. 278: 40305-40316, 2003.
Naik M, Benedikz E, Hernandez I, Libien J, Hrabe J, Valsamus M, Dow-Edwards D, Osman M, Sacktor TC. Expression of Protein Kinase M ? and the complete protein kinase C isoform family in rat brain. J. Comp. Neurol. 426: 243-358, 2000.
Education and Training
1992 – 2001; MD PhD, SUNY-Downstate
2001-2005; Anatomic Pathology / Neuropathology Residency, New York Presbyterian Hospital - Columbia University Medical Center
Wei-ping Chen, MD PhD: x 5095 (internal); email@example.com
Lab: (718) 270-8970