Ricardo Mostany

Tulane University

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Prasad V. G. Katakam

Tulane University

Venkata N. Sure

Tulane University

Wesley R. Evans

Rutgers, The State University of New Jersey

Siva S. V. P. Sakamuri

Tulane University

ÁP

Ángel Pazos

Universidad de Cantabria

Carlos Portera‐Cailliau

University of California, Los Angeles

David W. Busija

Tulane University

Elsa M. Valdizán

Centro de Investigación Biomédica en Red de Salud Mental

Lahari Kolli

Tulane University

Sarah H. Lindsey

Tulane University

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Tulane University

120

University of New Orleans

Consejo Superior de Investigaciones Científicas

Harvard University

Instituto de Salud Carlos III

Universidad de Cantabria

Baylor College of Medicine

University of Missouri

Instituto de Biomedicina y Biotecnología de Cantabria

Centro de Investigación Biomédica en Red de Salud Mental

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Genetic Deficiency of p53 Leads to Structural, Functional, and Synaptic Deficits in Primary Somatosensory Cortical Neurons of Adult Mice

Frontiers in Molecular Neuroscience (2022)

Haixia Kuang Tao Liu Cui Jiao Jianmei Wang Shi‐Nan Wu

The tumor suppressor p53 plays a crucial role in embryonic neuron development and neurite growth, and its involvement in neuronal homeostasis has been proposed. To better understand how the lack of the p53 gene function affects neuronal activity, spine development, and plasticity, we examined the electrophysiological and morphological properties of layer 5 (L5) pyramidal neurons in the primary somatosensory cortex barrel field (S1BF) by using in vitro whole-cell patch clamp and in vivo two-photon imaging techniques in p53 knockout (KO) mice. We found that the spiking frequency, excitatory inputs, and sag ratio were decreased in L5 pyramidal neurons of p53KO mice. In addition, both in vitro and in vivo morphological analyses demonstrated that dendritic spine density in the apical tuft is decreased in L5 pyramidal neurons of p53KO mice. Furthermore, chronic imaging showed that p53 deletion decreased dendritic spine turnover in steady-state conditions, and prevented the increase in spine turnover associated with whisker stimulation seen in wildtype mice. In addition, the sensitivity of whisker-dependent texture discrimination was impaired in p53KO mice compared with wildtype controls. Together, these results suggest that p53 plays an important role in regulating synaptic plasticity by reducing neuronal excitability and the number of excitatory synapses in S1BF.

Barrel cortex

Premovement neuronal activity

Cellular neuroscience

Neurite

10.3389/fnmol.2022.871974

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Citations (8)

A role for nuclear β-catenin in SNRI antidepressant-induced hippocampal cell proliferation

Neuropharmacology (2008)

Ricardo Mostany Elsa M. Valdizán Ángel Pazos

Subgranular zone

Reuptake

10.1016/j.neuropharm.2008.04.012

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Citations (43)

Abstract TP248: Nos Inhibitor Is An Effective Adjuvant To Reperfusion Therapy In Ischemic Stroke In Mice

Stroke (2022)

William P. Wisen Wesley R. Evans Venkata N. Sure Siva S. V. P. Sakamuri Lahari Kolli

Background: Inhibition nitric oxide synthase (NOS) has been shown to paradoxically protect against ischemic brain injury by an unknown mechanism. Recently, we found that NOS inhibitor, N (gamma)-nitro-L-arginine methyl ester (L-NAME), protects primary cultures of endothelial cells and neurons against oxygen-glucose deprivation-reoxygenation injury by preventing NOS uncoupling. Thus, the objective of the present study was to demonstrate the effectiveness of locally administered L-NAME against ischemia-reperfusion (I-R) injury. Methods: Transient focal cerebral ischemia in male mice (C57Bl/6, 2-4 months) was achieved by filament method of MCAO with a 60 min occlusion. We employed a novel approach to inject L-NAME (1 mg/Kg dosages at a rate of 60 ug/minute) locally into the ischemic zone by threading a catheter up the middle cerebral artery. This was timed to the onset of reperfusion by rapidly followng the removal of the occlusion with silicon suture. Following 24-hour reperfusion, infarct size was determined by 2,3,5-Triphenyltetrazolium chloride (TTC) staining and neurological functioning was recorded employing standard neurological score (0-4 range) and Rotarod performance test. Results: Admnistration of FITC Dextran 40K and fluroscence microscopy of the brain slices 1 hour post-ischemia confirmed the effective delivery of injected L-NAME into ischemic tissue. Localized injection of L-NAME was protective against I-R injury and promoted significant recovery of neurological and motor function (Figure). Conclusion: NOS inhibition could serve as an adjuvant for reperfusion therapies of ischemic stroke.

Stroke

10.1161/str.53.suppl_1.tp248

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Targeting TRAF3IP2 inhibits angiogenesis in glioblastoma

Frontiers in Oncology (2022)

Amin Izadpanah Fatemeh Daneshimehr Kurtis Willingham Zahra Barabadi Stephen E. Braun

Increased vascularization, also known as neoangiogenesis, plays a major role in many cancers, including glioblastoma multiforme (GBM), by contributing to their aggressive growth and metastasis. Although anti-angiogenic therapies provide some clinical improvement, they fail to significantly improve the overall survival of GBM patients. Since various pro-angiogenic mediators drive GBM, we hypothesized that identifying targetable genes that broadly inhibit multiple pro-angiogenic mediators will significantly promote favorable outcomes. Here, we identified TRAF3IP2 (TRAF3-interacting protein 2) as a critical regulator of angiogenesis in GBM. We demonstrated that knockdown of TRAF3IP2 in an intracranial model of GBM significantly reduces vascularization. Targeting TRAF3IP2 significantly downregulated VEGF, IL6, ANGPT2, IL8, FZGF2, PGF, IL1β, EGF, PDGFRB, and VEGFR2 expression in residual tumors. Our data also indicate that exogenous addition of VEGF partially restores angiogenesis by TRAF3IP2-silenced cells, suggesting that TRAF3IP2 promotes angiogenesis through VEGF- and non-VEGF-dependent mechanisms. These results indicate the anti-angiogenic and anti-tumorigenic potential of targeting TRAF3IP2 in GBM, a deadly cancer with limited treatment options.

10.3389/fonc.2022.893820

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Stable Density and Dynamics of Dendritic Spines of Cortical Neurons Across the Estrous Cycle While Expressing Differential Levels of Sensory-Evoked Plasticity

Frontiers in Molecular Neuroscience (2018)

Bailin H. Alexander Heather M. Barnes Emma H. Trimmer Andrew M. Davidson Benard O. Ogola

Periodic oscillations of gonadal hormone levels during the estrous cycle exert effects on the female brain, impacting cognition and behavior. While previous research suggests that changes in hormone levels across the cycle affect dendritic spine dynamics in the hippocampus, little is known about the effects on cortical dendritic spines and previous studies showed contradictory results. In this in vivo imaging study, we investigated the impact of the estrous cycle on the density and dynamics of dendritic spines of pyramidal neurons in the primary somatosensory cortex of mice. We also examined if the induction of synaptic plasticity during proestrus, estrus, and metestrus/diestrus had differential effects on the degree of remodeling of synapses in this brain area. We used chronic two-photon excitation (2PE) microscopy during steady-state conditions and after evoking synaptic plasticity by whisker stimulation at the different stages of the cycle. We imaged apical dendritic tufts of layer 5 pyramidal neurons of naturally cycling virgin young female mice. Spine density, turnover rate (TOR), survival fraction, morphology, and volume of mushroom spines remained unaltered across the estrous cycle, and the values of these parameters were comparable with those of young male mice. However, while whisker stimulation of female mice during proestrus and estrus resulted in increases in the TOR of spines (74.2 ± 14.9% and 75.1 ± 12.7% vs. baseline, respectively), sensory-evoked plasticity was significantly lower during metestrus/diestrus (32.3 ± 12.8%). In males, whisker stimulation produced 46.5 ± 20% increase in TOR compared with baseline-not significantly different from female mice at any stage of the cycle. These results indicate that, while steady-state density and dynamics of dendritic spines of layer 5 pyramidal neurons in the primary somatosensory cortex of female mice are constant during the estrous cycle, the susceptibility of these neurons to sensory-evoked structural plasticity may be dependent on the stage of the cycle. Since dendritic spines are more plastic during proestrus and estrus than during metestrus/diestrus, certain stages of the cycle could be more suitable for forms of memory requiring de novo formation and elimination of spines and other stages for forms of memory where retention and/or repurposing of already existing synaptic connections is more pertinent.

10.3389/fnmol.2018.00083

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A Method for 2-Photon Imaging of Blood Flow in the Neocortex through a Cranial Window

Journal of Visualized Experiments (2008)

Ricardo Mostany Carlos Portera‐Cailliau

The ability to image the cerebral vasculature (from large vessels to capillaries) and record blood flow dynamics in the intact brain of living rodents is a powerful technique. Using in vivo 2-photon microscopy through a cranial window it is possible to image fluorescent dyes injected intravenously. This permits one to image the cortical vasculature and also to obtain measurements of blood flow. This technique was originally developed by David Kleinfeld and Winfried Denk. The method can be used to study blood flow dynamics during or after cerebral ischemia, in neurodegenerative disorders, in brain tumors, or in normal brain physiology. For example, it has been used to study how stroke causes shifts in blood flow direction and changes in red blood cell velocity or flux in and around the infarct. Here we demonstrate how to use 2-photon microscopy to image blood flow dynamics in the neocortex of living mice using fluorescent dyes injected into the tail vein.

Neocortex

Two-photon excitation microscopy

10.3791/678-v

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Long-term treatment with fluoxetine induces desensitization of 5-HT4 receptors in rat hippocampus

Rebeca Vidal Elsa M. Valdizán Ricardo Mostany Ángel Pazos Elena Castro

5-HT4 receptor

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A Method for 2-Photon Imaging of Blood Flow in the Neocortex through a Cranial Window

Journal of Visualized Experiments (2008)

Ricardo Mostany Carlos Portera‐Cailliau

Neocortex

Two-photon excitation microscopy

10.3791/678

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Citations (49)

Cardiometabolic health, menopausal estrogen therapy and the brain: How effects of estrogens diverge in healthy and unhealthy preclinical models of aging

Frontiers in Neuroendocrinology (2023)

Jill M. Daniel Sarah H. Lindsey Ricardo Mostany Laura A. Schrader Andrea Zsombok

Research in preclinical models indicates that estrogens are neuroprotective and positively impact cognitive aging. However, clinical data are equivocal as to the benefits of menopausal estrogen therapy to the brain and cognition. Pre-existing cardiometabolic disease may modulate mechanisms by which estrogens act, potentially reducing or reversing protections they provide against cognitive decline. In the current review we propose mechanisms by which cardiometabolic disease may alter estrogen effects, including both alterations in actions directly on brain memory systems and actions on cardiometabolic systems, which in turn impact brain memory systems. Consideration of mechanisms by which estrogen administration can exert differential effects dependent upon health phenotype is consistent with the move towards precision or personalized medicine, which aims to determine which treatment interventions will work for which individuals. Understanding effects of estrogens in both healthy and unhealthy models of aging is critical to optimizing the translational link between preclinical and clinical research.

Cognitive aging

Cognitive Decline

Translational Research

10.1016/j.yfrne.2023.101068

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Citations (3)

Intravital Two-Photon Excitation Microscopy in Neuroscience: General Concepts and Applications

Springer eBooks (2014)

J. Tiago Gonçalves Ricardo Mostany

Two-photon excitation microscopy

Intravital microscopy

10.1007/978-94-017-9361-2_1

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Citations (1)