Neurochemical basis of cognitive enhancement in MK-801 animal model of schizophrenia : the role of enriched environment

211 p.Ingurune aberastua (IA) erabilera anitzeko eta balio terapeutiko handiko tresna da, baina gaixotasunneuropsikiatrikoetan duen balio potentziala ez da sakon aztertu. Ingurune aberastuak eskizofreniarensintoma kognitiboengan ondorio onuragarririk duen edo ez aztertzeak interes handia du, bai prebentziotresna gisa, bai sendabide gisa. Izan ere, ingurune aberastuak eragindako geneen aktibazio eta proteinensintesiak interneuronen adierazpena eta haien jarduera areagotu dezake. Honek, aldi berean, eraginzuzena izango luke portaeran eta kognizioan. Aldaketa hauek eskizofreniaren galera kognitiboakarintzeko funtsezkoak lirateke. Beraz, lan honen helburua MK-801 bidez sortutako eskizofrenia animaliereduan,bai portaeran zein maila zelularrean eta molekularrean garatutako alterazioak inguruneaberastuaren bidez nola aldatzen diren aztertzea da

Visual Outcomes and Management After Corneal Refractive Surgery: a Review

Corneal refractive surgery procedures are widely performed to permanently correct refractive errors. Overall, refractive surgeries are safe, predictable and present high rates of satisfaction. Nevertheless, the induced epithelial, stromal and nerve damage alters corneal integrity and function, triggering a regenerative response. Complications that arise from corneal wound healing process might directly impact on visual outcomes of keratorefractive procedures. Most of these complications can be prevented or effectively treated with minimal consequences and minor impact on optical quality. Nevertheless, it is crucial to accurately and timely identify these corneal regeneration-related complications for successful counseling and management. Optometrists, as primary eye care providers, play an essential role in detecting anatomic and functional alterations in vision. It is therefore of great interest for optometrists to be familiar with the principal postoperative complications derived from alterations in regenerative process after corneal laser refractive surgeries. This review aims to provide a basis for optometrists to better understand, identify and manage the main wound healing-related complications after refractive surgery.La cirugía refractiva corneal se lleva a cabo a menudo para corregir de manera permanente los errores refractivos. En general, la cirugía refractiva es segura y predecible, y presenta altos índices de satisfacción. Sin embargo, el daño inducido a nivel epitelial, estromal y nervioso altera la integridad y la función de la córnea, y desencadena una respuesta regenerativa. Las complicaciones que surgen del proceso de cicatrización de la herida corneal podrían tener un impacto directo sobre los resultados visuales de los procedimientos queratorefractivos. La mayoría de estas complicaciones pueden prevenirse, o tratarse de manera efectiva con mínimas consecuencias y un menor impacto sobre la calidad óptica. Sin embargo, es esencial identificar de manera precisa y oportuna dichas complicaciones relacionadas con la regeneración de la córnea, en aras de llegar a un asesoramiento y tratamiento satisfactorios. Los optometristas, al ser profesionales sanitarios de atención ocular primaria, juegan un papel esencial a la hora de detectar las alteraciones anatómicas y funcionales de la visión. Por tanto, es muy interesante que los optometristas estén familiarizados con las complicaciones postoperatorias principales derivadas de las alteraciones del proceso regenerativo tras cirugía refractiva corneal láser. Esta revisión tiene como objetivo proporcionar una base a los optometristas para la mejor comprensión, identificación y tratamiento de las principales complicaciones relacionadas con el proceso de cicatrización tras una cirugía refractiva

Differential Exposure to N-Ethyl N-Nitrosourea During Pregnancy is Relevant to the Induction of Glioma and PNSTs in the Brain

Exposure to N-nitroso compounds (NOCs) during pregnancy has been associated with an increase in brain tumors in the progeny. This study investigated the brain tumorigenic effect of N-ethyl N-nitrosourea (ENU) after differential exposure of rats during pregnancy. Sprague Dawley rats were exposed to a single dose of ENU (80 mg/kg) in three different circumstances: 1) at first, second or third week of gestation; 2) at the 15th embryonic day (E15) in consecutive litters and 3) at E15 in three successive generations. Location and characterization of the offspring's brain tumors were performed by magnetic resonance imaging and histopathological studies. Finally, tumor incidence and latency and the animals' survival were recorded. ENU-exposure in the last two weeks of pregnancy induced intracranial tumors in over 70% of the offspring rats, these being mainly gliomas with some peripheral nerve sheath tumors (PNSTs). Tumors appeared in young adults; glioma-like small multifocal neoplasias converged on large glioblastomas in senescence and PNSTs in the sheath of the trigeminal nerve, extending to cover the brain convexity. ENU-exposure at E15 in subsequent pregnancies lead to an increase in glioma and PNST incidence. However, consecutive generational ENU-exposure (E15) decreased the animals' survival due to an early onset of both types of tumors. Moreover, PNST presented an inheritable component because progeny, which were not themselves exposed to ENU but whose progenitors were, developed PNSTs. Our results suggest that repeated exposure to ENU later in pregnancy and in successive generations favours the development of intracranial gliomas and PNSTs in the offspring.This study has been financially supported by the University of the Basque Country (UPV/EHU) (GIU 092/19 and PPG 17/51) and the Basque Government (SAN20/25

Enriched Environment Reverts Somatostatin Interneuron Loss in MK-801 Model of Schizophrenia

Dysregulation of the inhibitory drive has been proposed to be a central mechanism to explain symptoms and pathophysiological hallmarks in schizophrenia. A number of recent neuroanatomical studies suggest that certain types of inhibitory cells are deficient in schizophrenia, including somatostatin-immunoreactive interneurons (SST+). The present study sought to use stereological methods to investigate whether the number of SST+ interneurons decreased after repeated injections of NMDA receptor antagonist MK-801 (0.5 mg/kg) and to determine the effect of limited exposure to an enriched environment (EE) in adult life on this sub-population of inhibitory cells. Considering that somatostatin expression is highly dependent on neurotrophic support, we explored the changes in the relative expression of proteins related to brain-derived neurotrophic factor—tyrosine kinase B (BDNF-TrkB) signaling between the experimental groups.We observed that early-lifeMK-801 treatment significantly decreased the number of SST+ interneurons in the medial prefrontal cortex (mPFC) and the hippocampus (HPC) of adult Long Evans rats. Contrarily, short-term exposure to EE increased the number of SST+ interneurons in MK-801-injected animals, except in the CA1 region of the hippocampus, whereas this increase was not observed in vehicle-injected rats. We also found upregulated BDNF-TrkB signaling after EE that triggered an increase in the pERK/ERK ratio in mPFC and HPC, and the pAkt/Akt ratio in HPC. Thus, the present results support the notion that SST+ interneurons are markedly affected after early-lifeNMDAR blockade and that EE promotes SST+ interneuron expression, which is partly mediated through the BDNF-TrkB signaling pathway. These results may have important implications for schizophrenia, as SST+ interneuron loss is also observed in the MK-801 pre-clinical model, and its expression can be rescued by non-pharmacological approaches.This work has been partially supported by the University of the Basque Country UPV/EHU (EHU 14/33, PPG 17/51) and by the Basque Government (GIC IT 901/16)

Alfa-sinukleina biomarkatzaile gisa Parkinson gaixotasunaren diagnostikoan

Parkinson disease (PD) is a common neurodegenerative disease, characterized pathologically by the presence of Lewy bodies and the progressive loss of dopaminergic neurons. Currently, the diagnosis of PD is based on clinical criteria; that is, it is diagnosed when motor symptoms appear such as limb tremor, slowness of movement or muscle stiffness. However, by the time motor symptoms appear, more than half of the dopaminergic neurons in the midbrain have been lost. Furthermore, as clinical diagnosis of PD is challenging, misdiagnosis is common. This highlights the need for disease-specific and early-stage biomarkers. Lewy bodies are rich in α-synuclein protein, who plays a fundamental role in the pathogenesis of PD. Therefore, α-synuclein may be useful as a PD biomarker. Therefore, the objective of this review is to summarize the efficacy of body fluid α-synuclein and its proteoforms measurements in the detection of PD. In fact, the identification of specific, sensitive, and non-invasive biomarkers is essential especially in regard to existing and future disease modifying treatments. Although the main candidate has been the measurement of α-synuclein in cerebrospinal fluid (CSF), CSF collection procedure is quite invasive and unsuitable in most clinical settings. Consequently, the presence of this protein and its proteoforms in biofluids such as blood plasma, saliva and tears has been investigated. Based on the results of these studies, phosphorylated and oligomeric α-synuclein are the best candidates for PD diagnosis. Until now, the measurement of α-synuclein has had multiple technical limitations, but the repeatability and reliability of immunoassays created in the last years has increased considerably. Therefore, it is expected that the potential of the main candidate biomarkers for PD diagnosis will be verified in the upcoming years.; Parkinson gaixotasuna ohiko gaixotasun neurodegeneratiboa da, patologikoki Lewy gorputzen presentziagatik eta neurona dopaminergikoen galera progresiboagatik bereizten dena. Gaur egun, Parkinson gaixotasunaren diagnostikoa irizpide klinikoetan oinarrituta dago; hau da, gorputz-adarren dardara, mugimenduen moteltasuna edo muskuluen gogortasuna bezalako sintoma motorrak agertzen direnean diagnostikatzen da. Hala ere, sintoma motorrak azaleratzen direnerako, mesentzefaloko neurona dopaminergikoen erdia baino gehiago galdu direla uste da. Gainera, Parkinsonaren diagnostiko klinikoa erronka bat denez, ohikoak dira diagnostiko okerrak. Horrek argi uzten du gaixotasunaren berariazko diagnostikorako biomarkatzaileak behar direla, batez ere fase goiztiarretan. Lewyren gorputzak aberatsak dira alfa-sinukleina (α-sinukleina) proteinatan, eta hauek funtsezko eginkizuna dute Parkinson gaixotasunaren patogenesian. Hori dela eta, α-sinukleina baliagarria izan daiteke Parkinsonaren biomarkatzaile gisa. Berrikuspen honen helburua, beraz, gorputzeko fluido desberdinetan α-sinukleinaren eta haren proteoformen neurketaren erabilgarritasun-diagnostikoari buruzko ebidentzia laburbiltzea da. Izan ere, espezifikoak, sentikorrak eta eskuragarriak diren biomarkatzaileak identifikatzea ezinbestekoa da Parkinson gaixotasuna aldatzeko dauden eta etorkizunean izango diren tratamenduei dagokienez. Nahiz eta hautagai nagusia α-sinukleina likido zefalorrakideoan (LZR) neurtzea izan den, LZR biltzeko prozedura nahiko inbaditzailea da, eta ez da egokia ingurune kliniko gehienetan. Ondorioz, odol-plasma, listua eta malkoa bezalako biofluidoetan ikertu da proteina honen eta haren proteoformen presentzia. Ikerketa hauen emaitzen arabera, α-sinukleina fosforilatua eta oligomerikoa izan daitezke hautagai egokienak Parkinson gaixotasunaren diagnostikorako. Orain arte α-sinukleinaren neurketak muga tekniko anitz izan dituen arren, azken urteetan sortutako tekniken bitartez entseguen errepikakortasuna eta fidagarritasuna nabarmen areagotu da. Beraz, hautagai nagusiek Parkinsonaren diagnostikorako biomarkatzailegisa izan dezaketen potentziala hurrengo urteetan egiaztatzea espero da

Sexu-desberdintasunak Parkinson gaixotasunean

Increasing evidence indicates that biological sex is an important factor in the development and phe-notypic expression of Parkinson’s disease. The prevalence of Parkinson’s disease affects men twice more often than women. However, women experience a more rapid progression of the disease. In addition, it is increasingly ac-knowledged that the frequency and/or severity of motor and non-motor symptoms are different in female and male patients with Parkinson’s disease. It is also considered that their response to pharmacological and surgical treat-ments differs significantly. Although the precise underlying mechanisms supporting sex differences are still to be elucidated, the pathophysiological underpinnings are presumably different in women and men with Parkinson’s dis-ease. This review aims to gather the current evidence regarding sex differences in clinical features, risk factors, pathophysiological mechanisms and response to treatments (pharmacological and surgical). Clarifying how the dis-ease affects each sex can improve patient care by tailoring the therapeutic management of men and women and by developing innovative programmes to respond to unmet needs.; Gero eta ebidentzia gehiagok adierazten du sexu biologikoa faktore garrantzitsua dela Parkinson gaixotasunaren garapenean eta adierazpen fenotipikoan. Jakina da Parkinson gaixotasunaren prebalentzia ia bi aldiz altuagoa dela gizonezkoetan emakumezkoetan baino. Hala ere, emakumezkoek gaixotasunaren progresio azkarragoa izaten dute. Gainera, azken urteotan egindako ikerketek agerian utzi dute Parkinson gaixotasunaren ondorioz agertzen diren sintoma motorrak eta ez-motorrak maiztasun edota larritasun desberdina dutela sexuaren arabera. Halaber, emakumeek eta gizonezkoek tratamendu farmakologikoen eta kirurgikoen aurrean duten erantzuna ere desberdina dela uste da. Sexu-desberdintasun hauen oinarriak zehatz-mehatz ezagutzen ez badira ere, mekanismo fisiopatologikoak desberdinak direla iradoki da. Berrikuspen honetan Parkinsona duten emakumezkoen eta gizonezkoen artean dauden desberdintasunak laburbiltzen dira, besteak beste, ezaugarri klinikoetan, arrisku-faktoreetan, gaixotasunaren fisiopatologian eta tratamenduen erantzunean. Patologiak sexu bakoitzari nola eragiten dion argitzeak pazienteen arreta hobetzea ahalbidetu dezake gizonen eta emakumeen maneiu terapeutikoa neurrira diseinatuz eta bakoitzaren beharrei erantzuteko programa berritzaileak garatuz

Short-Term Exposure to Enriched Environment in Adult Rats Restores MK-801-Induced Cognitive Deficits and GABAergic Interneuron Immunoreactivity Loss

Perinatal injections of N-methyl-D-aspartate (NMDA) receptor antagonist in rodents emulate some cognitive impairments and neurochemical alterations, such as decreased GABAergic (gamma aminobutyric acid) interneuron immunoreactivity, also found in schizophrenia. These features are pervasive, and developing neuroprotective or neurorestorative strategies is of special interest. In this work, we aimed to investigate if a short exposure to enriched environment (EE) in early adulthood (P55–P73) was an effective strategy to improve cognitive dysfunction and to restore interneuron expression in medial prefrontal cortex (mPFC) and hippocampus (HPC). For that purpose,we administered MK-801 intraperitoneally to Long Evans rats from postnatal days 10 to 20. Twenty-four hours after the last injection, MK-801 produced a transient decrease in spontaneous motor activity and exploration, but those abnormalities were absent at P24 and P55. The open field test on P73 manifested that EE reduced anxiety-like behavior. In addition, MK-801-treated rats showed cognitive impairment in novel object recognition test that was reversed by EE. We quantified different interneuron populations based on their calcium-binding protein expression (parvalbumin, calretinin, and calbindin), glutamic acid decarboxylase 67, and neuronal nuclei-positive cells by means of unbiased stereology and found that EE enhanced interneuron immunoreactivity up to normal values in MK- 801-treated rats. Our results demonstrate that a timely intervention with EE is a powerful tool to reverse long-lasting changes in cognition and neurochemical markers of interneurons in an animal model of schizophrenia.This study was supported by grants from the University of the Basque Country UPV/EHU (UFI 11/32) (EHU 14/33) and by the Government of the Basque Country (GIC IT 901/16). Murueta-Goyena A is financed by a predoctoral fellowship of the University of the Basque Country (UPV/EHU)

Foveal Pit Morphology Characterization: A Quantitative Analysis of the Key Methodological Steps

Disentangling the cellular anatomy that gives rise to human visual perception is one of the main challenges of ophthalmology. Of particular interest is the foveal pit, a concave depression located at the center of the retina that captures light from the gaze center. In recent years, there has been a growing interest in studying the morphology of the foveal pit by extracting geometrical features from optical coherence tomography (OCT) images. Despite this, research has devoted little attention to comparing existing approaches for two key methodological steps: the location of the foveal center and the mathematical modelling of the foveal pit. Building upon a dataset of 185 healthy subjects imaged twice, in the present paper the image alignment accuracy of four different foveal center location methods is studied in the first place. Secondly, state-of-the-art foveal pit mathematical models are compared in terms of fitting error, repeatability, and bias. The results indicate the importance of using a robust foveal center location method to align images. Moreover, we show that foveal pit models can improve the agreement between different acquisition protocols. Nevertheless, they can also introduce important biases in the parameter estimates that should be considered.This research was funded by the Department of Health of the Basque Government through the projects 2019111100 and 2020333033, Instituto de Salud Carlos III through the project PI16/00005 (Co-funded by European Regional Development Fund/European Social Fund “A way to make Europe”/”Investing in your future”) and the Basque Foundation for Health Innovation and Research (BIOEF) through the 2017 EITB Telemaratoia call (BIO17/ND/010)

Influence of ocular biometric factors on the defocus curve in an enlarged depth-of-focus intraocular lens

Background: To assess the influence of biometric measurements on the defocus curve after the implantation of enlarged depth-of-focus (EDoF) intraocular lens (IOL). Methods: Patients who underwent cataract surgery with bilateral implantation of Tecnis Symfony IOL were enrolled. Preoperatively, axial length (AL), corneal keratometry (K), pupil size and corneal aberrations were measured. 1 month after surgery, distance, intermediate, and near visual acuities (VA) were recorded. At 3 months, monocular and binocular corrected contrast sensitivities under photopic and mesopic lighting conditions were measured with CSV-1000E test. At 6-months, the defocus curve between −5.00 to + 3.00 diopters (D) was assessed in steps of 0.50 D, and NEI-RQL-42 questionnaire was administered. Results: One hundred thirty one eyes of 66 patients were included. Binocular logMAR VA better than 0.1 for intermediate vision was obtained in 90% of patients, whereas only 17.7% obtained that result in near vision. The rate of satisfaction was high (96%) and most of them (85.5%) had no or little difficulties in near vision. The mean amplitude of the defocus curve was 2.35D ± 0.73D, and smaller AL, smaller pupils, younger age, and male sex were associated with wider range of clear vision. Conclusions: Tecnis Symfony IOL enables functional vision at all distances, but demographic variables and preoperative biometric measurements like AL and pupil size influence the postoperative amplitude of the defocus curve. These parameters could be used to predict the performance of EDoF IOLs

Potential Tear Biomarkers for the Diagnosis of Parkinson’s Disease—A Pilot Study

Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease. In this study, the tear proteome profile of patients with idiopathic PD (iPD, n = 24), carriers of the E46K-SNCA mutation (n = 3) and healthy control (CT, n = 27) subjects was analyzed to identify candidate biomarkers for the diagnosis of PD. An observational, prospective and case-control pilot study was carried out, analyzing the participants tear samples by nano-liquid chromatography–mass spectrometry (nLC–MS/MS) and assessing their neurological impairment. The proteomic data obtained are available at ProteomeXchange with identifier 10.6019/PXD028811. These analyses led to the identification of 560 tear proteins, some of which were deregulated in PD patients and that have been implicated in immune responses, inflammation, apoptosis, collagen degradation, protein synthesis, defense, lipid transport and altered lysosomal function. Of these proteins, six were related to neurodegenerative processes and showed a good capacity to classify patients and controls. These findings revealed that certain proteins were upregulated in the tears of PD patients, mainly proteins involved in lysosomal function. Thus, in this study, tear proteins were identified that are implicated in neurodegeneration and that may be related to an aggressive disease phenotype in PD patients.This work was supported by MINECO-Retos Fondos Fender (RTC-2016-48231), Gobierno Vasco (PUE_2018_1_0004), ELKARTEK (KK-2019/00086), PIBA 2020-1-0026, MINECO-Retos (PID2019-111139RB-I00) and ELKARTEK (KK-2021/00023)