Cesar Ramon Romero Leguizamon, M.D., Ph.D.

@article{pmid34151857,

title = {α-Synuclein Responses in the Laterodorsal Tegmentum, the Pedunculopontine Tegmentum, and the Substantia Nigra: Implications for Early Appearance of Sleep Disorders in Parkinson's Disease},

author = {Altair B Dos Santos and Line K Skaanning and Eyd Mikkelsen and Cesar R Romero-Leguizamón and Morten P Kristensen and Anders B Klein and Siganya Thaneshwaran and Annette E Langkilde and Kristi A Kohlmeier},

url = {https://pubmed.ncbi.nlm.nih.gov/34151857/},

doi = {10.3233/JPD-212554},

issn = {1877-718X},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {J Parkinsons Dis},

volume = {11},

number = {4},

pages = {1773--1790},

abstract = {BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder associated with insoluble pathological aggregates of the protein α-synuclein. While PD is diagnosed by motor symptoms putatively due to aggregated α-synuclein-mediated damage to substantia nigra (SN) neurons, up to a decade before motor symptom appearance, patients exhibit sleep disorders (SDs). Therefore, we hypothesized that α-synuclein, which can be present in monomeric, fibril, and other forms, has deleterious cellular actions on sleep-control nuclei.



OBJECTIVE: We investigated whether native monomer and fibril forms of α-synuclein have effects on neuronal function, calcium dynamics, and cell-death-induction in two sleep-controlling nuclei: the laterodorsal tegmentum (LDT), and the pedunculopontine tegmentum (PPT), as well as the motor-controlling SN.



METHODS: Size exclusion chromatography, Thioflavin T fluorescence assays, and circular dichroism spectroscopy were used to isolate structurally defined forms of recombinant, human α-synuclein. Neuronal and viability effects of characterized monomeric and fibril forms of α-synuclein were determined on LDT, PPT, and SN neurons using electrophysiology, calcium imaging, and neurotoxicity assays.



RESULTS: In LDT and PPT neurons, both forms of α-synuclein induced excitation and increased calcium, and the monomeric form heightened putatively excitotoxic neuronal death, whereas, in the SN, we saw inhibition, decreased intracellular calcium, and monomeric α-synuclein was not associated with heightened cell death.



CONCLUSION: Nucleus-specific differential effects suggest mechanistic underpinnings of SDs' prodromal appearance in PD. While speculative, we hypothesize that the monomeric form of α-synuclein compromises functionality of sleep-control neurons, leading to the presence of SDs decades prior to motor dysfunction.},

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pubstate = {published},

tppubtype = {article}

}

@article{pmid32768153,

title = {Stress-related endogenous neuropeptides induce neuronal excitation in the Laterodorsal Tegmentum},

author = {Cesar R Romero-Leguizamón and Kristi A Kohlmeier},

url = {https://pubmed.ncbi.nlm.nih.gov/32768153/},

doi = {10.1016/j.euroneuro.2020.07.008},

issn = {1873-7862},

year  = {2020},

date = {2020-01-01},

urldate = {2020-01-01},

journal = {Eur Neuropsychopharmacol},

volume = {38},

pages = {86--97},

abstract = {Stress is a physiological response that promotes maintenance of balance against harmful stimuli. Unfortunately, chronic activation of stress systems facilitates the development of psychiatric disorders. A stress-mediated hypercholinergic state could underlie this facilitation, as cholinergic mechanisms have been suggested to play a role in anxiety, depression, and substance use disorder (SUD). Stimulation by stress hormones, urocortin (Ucn1) or corticotropin-releasing factor (CRF), of the CRF receptor type 1 (CRFR1) of acetylcholine-containing neurons of the laterodorsal tegmental nucleus (LDT) could be involved in modulation of cholinergic transmission during periods of stress hormone activation, which could play a role in psychiatric disorders as cholinergic LDT neurons project to, and control activity in, mood-, arousal- and SUD-controlling regions. The present study investigated for the first time the membrane effects and intracellular outcomes of CRFR1 activation by endogenous stress hormones on LDT neurons. Patch clamp recordings of immunohistochemically-identified cholinergic and non-cholinergic LDT neurons with concurrent calcium imaging were used to monitor cellular responses to CRFR1 stimulation with Ucn1 and CRF. Postsynaptically-mediated excitatory currents were elicited in LDT cholinergic neurons, accompanied by an enhancement in synaptic events. In addition, CRFR1 activation resulted in rises in intracellular calcium levels. CRFR1 stimulation recruited MAPK/ERK and SERCA-ATPase involved pathways. The data presented here provide the first evidence that Ucn1 and CRF exert pre and postsynaptic excitatory membrane actions on LDT cholinergic neurons that could underlie the hypercholinergic state associated with stress which could play a role in the heightened risk of psychiatric disorders associated with a chronic stress state.},

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pubstate = {published},

tppubtype = {article}

}

@article{pmid30728375,

title = {Increasing cellular lifespan with a flow system in organotypic culture of the Laterodorsal Tegmentum (LDT)},

author = {César R Romero-Leguizamón and Mohamed R Elnagar and Uffe Kristiansen and Kristi A Kohlmeier},

url = {https://pubmed.ncbi.nlm.nih.gov/30728375/},

doi = {10.1038/s41598-018-37606-3},

issn = {2045-2322},

year  = {2019},

date = {2019-01-01},

urldate = {2019-01-01},

journal = {Sci Rep},

volume = {9},

number = {1},

pages = {1486},

abstract = {Organotypic brain culture is an experimental tool widely used in neuroscience studies. One major drawback of this technique is reduced neuronal survival across time, which is likely exacerbated by the loss of blood flow. We have designed a novel, tube flow system, which is easily incorporated into the commonly-used, standard semi-permeable membrane culture methodology which has significantly enhanced neuronal survival in a brain stem nucleus involved in control of motivated and arousal states: the laterodorsal tegmental nucleus (LDT). Our automated system provides nutrients and removes waste in a comparatively aseptic environment, while preserving temperature, and oxygen levels. Using immunohistochemistry and electrophysiology, our system was found superior to standard techniques in preserving tissue quality and survival of LDT cells for up to 2 weeks. In summary, we provide evidence for the first time that the LDT can be preserved in organotypic slice culture, and further, our technical improvements of adding a flow system, which likely enhanced perfusion to the slice, were associated with enhanced neuronal survival. Our perfusion system is expected to facilitate organotypic experiments focused on chronic stimulations and multielectrode recordings in the LDT, as well as enhance neuronal survival in slice cultures originating from other brain regions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {The relationship between the components of idiopathic focal epilepsy},

author = {Romero-Leguizamón, César R},

doi = {10.15406/jpnc.2018.08.00321},

year  = {2018},

date = {2018-08-01},

urldate = {2018-08-01},

journal = {izamon CRR. The relationship between the components of idiopathic focal epilepsy. },

volume = {8},

number = {3},

pages = {113-119},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid31069033,

title = {Morphine in Plasma and Cerebrospinal Fluid of Patients Addicted to Opiates Undergoing Surgery: High-performance Liquid Chromatography Method},

author = {Mohammad Ali Haghbin and Zia Navidi and Cesar R Romero-Leguizamon and Mohammad Shabani},

url = {https://pubmed.ncbi.nlm.nih.gov/31069033/},

doi = {10.22122/ahj.v10i2.538},

issn = {2008-4633},

year  = {2018},

date = {2018-04-01},

urldate = {2018-04-01},

journal = {Addict Health},

volume = {10},

number = {2},

pages = {95--101},

abstract = {Background: The prevalence of opium addiction among Iranians is considerable. Since endogenous opioid systems may be altered as a consequence of addiction, it is very important to determine the plasma and cerebrospinal fluid (CSF) levels of morphine in Iranian patients addicted to opiates who will undergo surgery.



Methods: We obtained CSF and plasma samples from 50 volunteers with an established opioid addiction pattern. Samples were analyzed using high-performance liquid chromatography (HPLC). Additionally, frequency of nausea and vomiting, baseline heart rate (BHR), and systolic blood pressure (SBP) were recorded within the surgery and postoperatively during a 10-min interval.



Findings: 84% of participants were men with a median age of 39.08 years. Mean score of body mass index (BMI) was 23.30 and most of the participants (46%) used opium in its traditional inhaled form. A higher concentration of morphine in blood was found in comparison with CSF (P < 0.001) in relation to the way of use. However, no statistically significant differences were found in relation to the type of addictive substance. No other association was found between the levels of morphine and the clinical characteristics of the patients. Moreover, results revealed no difference between hemodynamic-related data with blood and CSF level in opium-dependent patients.



Conclusion: Quantification of plasma and CSF morphine, both immediately before initiation of surgery and subsequently on recovery room, showed that although clinical efficacy of systemic morphine was poor in addicted patients, it had no effect on patients' hemodynamic variable and following complications after surgery.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{ROMEROLEGUIZAMON2018359,

title = {Medicine: art or science? A reflection on the arts in medical education},

author = {César Ramón Romero Leguizam},

url = {http://www.sciencedirect.com/science/article/pii/S1575181317301018},

doi = {https://doi.org/10.1016/j.edumed.2017.04.005},

issn = {1575-1813},

year  = {2018},

date = {2018-01-01},

urldate = {2018-01-01},

journal = {Educación Médica},

volume = {19},

number = {6},

pages = {359 - 368},

abstract = {The situation of health systems in the world is critical, however, within this panorama medical education provides strategies that allow changes to be generated. A reflection is raised about the importance of complementing the training of the medical student with the development of humanistic skills. Would the above allow a clinical exercise with judgment and reasoning, without neglecting the component of service, kindness, cordiality, listening and fraternity? This article tries to answer this concern, reflecting on some situations that condition medical training, and exposes numerous examples of doctors from different periods of history and latitudes (Europe, Asia and America) that have successfully complemented the practice of their profession and the execution of arts such as literature, painting and theater, among others. Among them are Albert Schweitzer, a German national, winner of the Nobel Peace Prize in 1952 and Jorge Drexler, Uruguayan, Oscar Award from the Academy of Motion Picture Arts and Sciences of the United States, for Best Soundtrack in 2005 Finally, consideration is given to having academic and extra-academic spaces that benefit medical training complemented by artistic and humanistic skills.},

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pubstate = {published},

tppubtype = {article}

}