Zahra Dargaei

All Publications

• Cortical interneuron-mediated inhibition delays the onset of amyotrophic lateral sclerosis BRAIN Khademullah, C., Aqrabawi, A. J., Place, K. M., Dargaei, Z., Liang, X., Pressey, J. C., Bedard, S., Yang, J., Garand, D., Keramidis, I., Gasecka, A., Cote, D., De Koninck, Y., Keith, J., Zinman, L., Robertson, J., Kim, J., Woodin, M. A. 2020; 143: 800–810

  Abstract

  Amyotrophic lateral sclerosis is a fatal disease resulting from motor neuron degeneration in the cortex and spinal cord. Cortical hyperexcitability is a hallmark feature of amyotrophic lateral sclerosis and is accompanied by decreased intracortical inhibition. Using electrophysiological patch-clamp recordings, we revealed parvalbumin interneurons to be hypoactive in the late pre-symptomatic SOD1*G93A mouse model of amyotrophic lateral sclerosis. We discovered that using adeno-associated virus-mediated delivery of chemogenetic technology targeted to increase the activity of the interneurons within layer 5 of the primary motor cortex, we were able to rescue intracortical inhibition and reduce pyramidal neuron hyperexcitability. Increasing the activity of interneurons in the layer 5 of the primary motor cortex was effective in delaying the onset of amyotrophic lateral sclerosis-associated motor deficits, slowing symptom progression, preserving neuronal populations, and increasing the lifespan of SOD1*G93A mice. Taken together, this study provides novel insights into the pathogenesis and treatment of amyotrophic lateral sclerosis.

  View details for DOI 10.1093/brain/awaa034

  View details for Web of Science ID 000522641900018

  View details for PubMedID 32203578

• Alterations in Hippocampal Inhibitory Synaptic Transmission in the R6/2 Mouse Model of Huntington's Disease. Neuroscience Dargaei, Z. n., Liang, X. n., Serranilla, M. n., Santos, J. n., Woodin, M. A. 2019; 404: 130–40

  Abstract

  Huntington's disease (HD) is a genetic neurodegenerative disorder of the central nervous system characterized by choreatic movements, behavioral and psychiatric disturbances and cognitive impairments. Deficits in learning and memory are often the first signs of disease onset in both HD patients and mouse models of HD and are in part regulated by the hippocampus. In the R6/2 mouse model of HD, GABAergic transmission can be excitatory in the hippocampus and restoring inhibition can rescue the associated memory deficits. In the present study we determine that hippocampal GABAergic neurotransmission in the R6/2 mouse is disrupted as early as 4 weeks of age and is accompanied by alterations in the expression of key inhibitory proteins. Specifically, spontaneous inhibitory postsynaptic currents were initially increased in frequency at 4 postnatal weeks and subsequently decreased after the mice displayed the typical R6/2 behavioral phenotype at 10 weeks of age. Symptomatic mice also exhibited a change in the probability of GABA release and changes in the basic membrane properties including neuronal excitability and input resistance. These electrophysiological changes in presymptomatic and symptomatic R6/2 mice were further accompanied by alterations in the protein expression level of pre- and postsynaptic inhibitory markers. Taken together, the present findings demonstrate profound alterations in the inhibitory neurotransmission in the hippocampus across the lifespan of the disease, including prior to neuronal degeneration, which suggests that the inhibitory hippocampal synapses may prove useful as a target for future therapeutic design.

  View details for DOI 10.1016/j.neuroscience.2019.02.007

  View details for PubMedID 30797895

• Restoring GABAergic inhibition rescues memory deficits in a Huntington’s disease mouse model Proceedings of the National Academy of Sciences of the United States of America (PNAS) Dargaei, Z., Bang, J. Y., Mahadevan, V., Khademullah, C., Bedard, S., Parfitt, G. M., Kim, J., Woodin, M. 2018

  View details for DOI 10.1073/pnas.1716871115

• Native KCC2 interactome reveals PACSIN1 as a critical regulator of synaptic inhibition eLife Mahadevan, V., Khademullah, C., Dargaei, Z., Chevrier, J., Pavel, U., Kwan, J., Bagshaw , R. D., Pawson, T., Emili, A., De Koninck , Y., Anggono, V., Airaksinen, M., Woodin, M. A. 2017; 6:e28270

  View details for DOI 10.7554/eLife.28270

• A kainate receptor subunit promotes the recycling of the neuron-specific K+-Cl- co-transporter KCC2 in hippocampal neurons Journal of Biological Chemistry Pressey, J. C., Mahadevan, V., Khademullah, C., Dargaei, Z., Chevrier, J., Ye, W., Huang, M., Chauhan, A. K., Meas, S. J., Uvarov, P., Airaksinen, M., Woodin, M. A. 2017; 292(15):6190-6201

  View details for DOI 10.1074/jbc.M116.767236

• Top-down modulation of olfactory-guided behaviours by the anterior olfactory nucleus pars medialis and ventral hippocampus Nature Communications Aqrabawi, A. J., Browne, C. J., Dargaei, Z., Garand, D., Khademullah, C., Woodin, M. A., Kim, J. 2016; 7:13721

  View details for DOI 10.1038/ncomms13721

• Misregulation of an Activity-Dependent Splicing Network as a Common Mechanism Underlying Autism Spectrum Disorders Molecular Cell Quesnel-Vallières, M., Dargaei, Z., Irimia, M., Gonatopoulos-Pournatzis, T., Ip, J. Y., Wu, M., Sterne-Weiler, T., Nakagawa, S., Woodin, M. A., Blencowe, B. J., Cordes, S. P. 2016; 64(6):1023-1034

  View details for DOI 10.1016/j.molcel.2016.11.033

• Neto2-null mice have impaired GABAergic inhibition and are susceptible to seizures Frontiers in Cellular Neuroscience Mahadevan, V., Dargaei, Z., Ivakine, E., Hartmann, A., Ng, D., Chevrier, J., Ormond, J., Nothwang, H. G., McInnes, R. R., Woodin, M. A. 2015; 23;9:368

  View details for DOI 10.3389/fncel.2015.00368

• Ca2+-induced uncoupling of Aplysia bag cell neurons Journal of Neurophysiology Dargaei, Z., Standage, D., Groten, C. J., Blohm, G., Magoski, N. S. 2015; 113(3):808-21

  View details for DOI 10.1152/jn.00603.2014

• Electrical coupling between Aplysia bag cell neurons: characterization and role in synchronous firing Journal of Neurophysiology Dargaei, Z., Colmers, P. L., Hodgson, H. M., Magoski, N. S. 2014; 112(11):2680-96

  View details for DOI 10.1152/jn.00494.2014

• Retinal region of polarization sensitivity switches during ontogeny of rainbow trout Journal of Neuroscience Sabbah, S., Habib-Nayany, M. F., Dargaei, Z., Hauser, F. E., Kamermans, M., Hawryshyn, C. W. 2013; 33(17):7428-38

  View details for DOI 10.1523/JNEUROSCI.5815-12.2013