Renata Batista-Brito, Ph.D

Assistant Professor, Dominick P. Purpura Department of Neuroscience

Assistant Professor, Genetics

(neuroscience category)

Roles of gap junctions in excitable and inexcitable cells Research of our laboratory is centered on physiological and cell/molecular biological studies of gap junctions, the intercellular channels that allow cells to directly exchange ions and metabolites. In the nervous system, gap junctions form electrotonic synapses between neurons, permitting synchronized excitation of coupled cells, and they couple glia into a complex interconnected network where information is exchanged through calcium waves and metabolically. Major projects of the laboratory are attempting to resolve (1) role of gap junctions and extracellular signaling in a mouse model of orofacial pain, (2) how connexin-protein interactions (which result in a dynamic complex that we term the “Nexus”) deliver, assemble and modulate gap junctions in various cell types, (3) the role of gap junctions in stem cell therapy in a mouse model of Chagas disease (with H.B. Tanowitz, Dept Pathology), (4) endothelial cell and astrocyte mechanotransduction and cell polarization in a blood-brain-barrier model (with members of the Biomedical Engineering Department, CCNY). These studies utilize a variety of preparations, including primary cultures of cells from transgenic mice with altered expression of connexin and other genes and transfection of wildtype and mutated connexin sequences into communication deficient cell lines, where small high resistance cells permit structure-function analysis at the single channel level. Techniques include intracellular recordings with conventional and ion-selective microelectrodes, photomanipulation such as FRAP, optical monitoring of intracellular ionic activities (especially Ca2+ and propagated Ca2+ waves), patch clamp recording of single channels and whole cell currents and standard molecular biological and immunological methods such as Northern and Western blot analyses, immunostaining and RT-PCR and expression profiling using microarrays.

Panx1 controls DRG neuron maturation in culture.  A: sensory neurons isolated from WT mice extend long processes at 4 days of NGF treatment ; B: sensory neurons isolated from Panx1 KO mice extend short processes at 4 days of NGF treatment; C,D,E: Axon and dendrite length and complexity are significantly lower in Panx1 KO mice; F: Soma diameter is significantly larger in Panx1 KO mice; (N=5;  *, P<0.05; **, P< 0.01) ; Images in A and B stained with NF200 (Green) antibody and the nuclear marker DAPI (Blue)

Selected Publications

Boudewyn, L.C., Sikora, J., Kuchar, L., Ledvinova, J., Grishchuk, Y., Wang, S., Dobrenis, K., Walkley, S.U. N-butyl-deoxynojirimycin delays motor deficits, cerebellar microgliosis and Purkinje cell loss in a mouse model of mucolipidosis type IV. Neurobiol. Disease, 105:257-270, 2017.

Trilck, M., Peter, F., Zheng, C., Frank, M., Dobrenis, K., Mascher, H., Rolfs, A., Frech, M.J. Diversity of glycosphingolipid GM2 and cholesterol accumulation in NPC1 patient-specific iPSC-derived neurons. Brain Res. 1657:52-61, 2017.

Yang, D.-S., Stavrides, P., Kumar, K., Jiang, Y, Mohan, PS., Ohno, M., Dobrenis, K., Davidson, C.D., Saito, M, Pawlik, M., Huo, C., Walkley, S.U., Nixon, R.A. Cyclodextrin has conflicting actions on autophagy flux in vivo in brains of normal and Alzheimer model mice. Human Mole. Genet. 26:843-859, 2017.

Davidson, C., Fishman, YI, Puskas I., Szeman, J., Sohajda, T., McCauliff, L.A., Sikora, J., Storch, J., Vanier M.T., Szente, L., Walkley, S.U., Dobrenis, K. Efficacy and ototoxicity of different cyclodextrins in Niemann-Pick C disease. Ann Clin Transl Neurol. 3:366-380, 2016.

Saito, M., Wu, G., Hui, M., Masiello, K., Dobrenis, K., Ledeen, R.W., Saito, M. Ganglioside accumulation in activated glia in the developing brain: comparison between WT and GalNacT KO mice. J. Lipid Res. 56:1434-1448, 2015.

Farfel-Becker, T., Vitner, E.B., Kelly, S.L., Bame, J.R., Duan, J., Shinder, V., Merrill Jr, A.F., Dobrenis, K., Futerman, A.H. Neuronal accumulation of glucosylceramide in a mouse model of neuronopathic Gaucher disease leads to neurodegeneration. Human Molec. Genet 23:843-854, 2014. 

Micsenyi, M.C., Sikora, J., Stephney, G., Dobrenis, K., Walkley, S.U. Lysosomal membrane permeability stimulates protein aggregate formation in neurons of a lysosomal disease. J. Neurosci. 33:10815-10827, 2013.

Erblich, B., Zhu, L., Etgen, A., Dobrenis, K., Pollard, J.W. Absence of colony stimulating factor-1 receptor signaling results in loss of microglia, disrupted brain development and olfactory deficits. PloS One, 2011. 2011;6(10):e26317. Epub 2011 Oct 27.

Stromme, P., Dobrenis, K., Sillitoe, R.V., Gulinello, M., Ali, N.F., Davidson, C., Micsenyi, M.C., Stephney, G., Ellevog, L., Klunglund, A., Walkley, S.U. X-linked Angelman-like syndrome caused by Slc9a6 knockout in mice exhibits evidence of endosomal-lysosomal dysfunction. Brain 134:3369-83, 2011.

Gulinello, M., Chen, F., Dobrenis, K. Early deficits in motor coordination, cognitive function and anxiety-like behavior in a mouse model of the neurodegenerative lysosomal storage disorder, Sandhoff disease. Behav. Brain Res. 193:315-319, 2008.

Dermietzel, R. and Spray DC. (2012 Blood-Brain-Barrier and the Neural-Vascular Unit. In Astrocytes: Wiring the Brain, Eds: E. Scemes and DC Spray. Taylor & Francis, CRC Press. pp. 179­–203.
 
Dermietzel R and Spray DC (2012) Gap Junctions and Electrical Synapses In Textbook of Neuroscience in the 21st Century: Basic and Clinical. Heidelberg: Springer Verlag.Editor-in-Chief: D.W. Pfaff.
 
Hanani M and Spray DC (2012) Chapter 11. Glial cells in autonomic and sensory ganglia In: Neuroglia. Eds: H. Kettenmann and B. Ransom. Oxford University Press, in press. pp. 122­–133.
 
Dermietzel, R. and Spray, D.C. (Eds) (2012) Electrical synapses: From the lab to the clinic. Brain Research Reviews Special Issue
Wu D, Schaffler MB, Weinbaum S, Spray DC. Matrix-dependent adhesion mediates network responses to physiological stimulation of the osteocyte cell process. Proc Natl Acad Sci U S A. 2013 Jul 16;110(29):12096–101.
 
Spray DC, Hanstein R, Lopez-Quintero SV, Stout RF Jr, Suadicani SO, Thi MM. Gap junctions and Bystander Effects: Good Samaritans and executioners. Wiley Interdiscip Rev Membr Transp Signal. 2013 Jan;2(1):1–15.
 
Bejarano E, Yuste A, Patel B, Stout RF Jr, Spray DC, Cuervo AM. Connexins modulate autophagosome biogenesis. Nat Cell Biol. 2014 May;16(5):401–14.
 
Jasmin, Jelicks LA, Tanowitz HB, Peters VM, Mendez-Otero R, Campos de Carvalho AC, Spray DC. Molecular imaging, biodistribution and efficacy of mesenchymal bone marrow cell therapy in a mouse model of Chagas disease. Microbes Infect. 2014 Nov;16(11):923–35.
 
Thi MM, Suadicani SO, Schaffler MB, Weinbaum S, Spray DC. Mechanosensory responses of osteocytes to physiological forces occur along processes and not cell body and require ±V≤3 integrin. Proc Natl Acad Sci U S A. 2013 Dec 24;110(52):21012–7.