Garikoitz Azkona

Euskal Herriko Unibertsitatea (UPV/EHU)

Extensive literature has reported a link between social stress and mental health. In this complex relationship, individual strategies for coping with social stress are thought to have a possible modulating effect, with sociability being a key factor. Despite the higher incidence of affective disorders in females and sex-related neurochemical differ...

Fear-related pathologies are among the most prevalent psychiatric conditions, having inappropriate learned fear and resistance to extinction as cardinal features. Exposure therapy represents a promising therapeutic approach, the efficiency of which depends on inter-individual variation in fear extinction learning, which neurobiological basis is unk...

Chronic social stress can increase susceptibility to chronic diseases such as depression. One of the most used models to study the physiological mechanisms and behavioral outcomes of this type of stress is chronic defeat stress (CDS) in male mice. OF1 male mice were subjected to a stress period lasting 18 days. During that time, non-stressed animal...

Evidence indicates that chronic social stress plays a significant role in the development of cancer and depression. Although their association is recognized, the precise physiological mechanism remains unknown. In our previous work, we observed that OF1 males subjected to chronic social defiance exhibited anhedonia, and those who developed tumors i...

Social stress is the most significant source of chronic stress in humans and is commonly associated with health impairment. Individual differences in the behavioral coping responses to stress have been proposed to mediate the negative effects of stress on physical, behavioral and mental health. Animal models, particularly mice, offer valuable insig...

The 3Rs principle (replacement, reduction and refinement) is not only the cornerstone of current legislation on the use of laboratory animals, but also the framework that allows for us to think about and evaluate the benefits and harms of using animals in biomedical research. It is, therefore, of great interest to be able to share both the theoreti...

Animal facility personnel provide the husbandry and care of laboratory animals. We aimed to investigate their work-related quality of life, empathy and mental well-being. Participants living in Spain were contacted by email and asked to complete an anonymous online questionnaire, in which they answered the Professional Quality of Life scale, the Co...

Animalien erabilera zientzia biomedikoan eztabaidagarria da oraindik. Gizabanako baten animaliekiko kezka-maila, beraien kulturak, animaliekiko lehenagoko edo oraingo esperientziak eta animali espezie konkretuek eragiten dute. Ikerketa honetan, Euskal Herriko Unibertsitateko (UPV/EHU) laborategiko animaliekin lan egiten duten ikertzaileen iritzia j...

Gaur egun, gero eta sarriagoak dira inolako etiologia zehatz gabeko gaixotasun eta nahasmenduak. Eguneroko estresa min kronikoa garatzeko arrisku faktorea da. Migraina min kroniko posible horietako bat da. Badakigu, estres kronikoa antsietatearekin eta depresioarekin gehien lotzen den faktorea dela. Antsietatea eta depresioak eragin dezaketen estre...

The regulatory framework for the use of animals in research in many countries is based on the 3Rs: replacement, reduction, and refinement [...]

• El 6% de los encuestados indican bajos niveles de satisfacción por compasión, lo que indica que su trabajo no les proporciona satisfacción. • El 65,8% y el 86,7% de los encuestados indicaron niveles medio-alto de estrés traumático secundario y burn out, respectivamente, lo que indica que en su trabajo perciben niveles medio-altos de estrés. • Los...

Fear-related pathologies are among the most prevalent psychiatric conditions, having inappropriate learned fear and resistance to extinction as cardinal features. Exposure therapy represents a promising therapeutic approach, the efficiency of which depends on inter-individual variation in fear extinction learning, though neurobiological basis is un...

In the last years, different research groups have made considerable efforts to improve the care and use of animals in research. Mice (Mus musculus) are the most widely used animal species in research in the European Union and are sociable and hierarchical creatures. During experiments, researchers tend to individualize males, but no consideration i...

Ingurumen-estimulu batek garuneko neurokimikan aldaketak eragin ditzake, nahasmendu neuropsikiatrikoak eraginez. Ildo horretan, isolamendu sozialak eragindako bakardade-sentimenduek estres kronikoarengan eragin dezakete. Estres kronikoak aldaketa neuroendokrinoak eta immunologikoak eragiten ditu eta aldaketa horiek serotonina maila gutxitzea eragin...

Esperimentuetan eta bestelako zientzia egitasmoetan erabilitako animaliak babesteko oinarrizko arauak ezartzen dituen otsailaren 1eko 53/2013 Errege Dekretuaren 1. artikuluak zehazten du dekretuaren helburua hau dela: «animalien erabilera ordezkatzea eta murriztea prozeduretan eta prozedura horietan animalien hazkuntza, ostatua, zaintza eta erabile...

El Real Decreto 53/2013, de 1 de febrero, por el que se establecen las normas básicas aplicables para la protección de los animales utilizados en experimentación y otros fines científicos, incluyendo la docencia, en su artículo 1, describe como objeto del mismo, «el reemplazo y reducción de la utilización de animales en procedimientos y el refinami...

Refining experiments and housing conditions so as to cause the minimum possible pain and distress is one of the three principles (3Rs) on which Directive 2010/63/EU is based. In this systematic review, we aimed to identify and summarize published advances in the refinement protocols made by European Union-based research groups from 2011 to 2021, an...

Background: In Spain, the perceived professional quality of life among veterinarians has not been explored. Methods: Veterinarians were invited to complete an online questionnaire in which they answered the Professional Quality of Life scale, the Medical Outcomes Study Social Support Survey and the Warwick-Edinburgh Mental Well-Being Scale. Part...

Extensive literature has reported a link between stress and tumor progression, and between both of these factors and mental health. Despite the higher incidence of affective disorders in females and the neurochemical differences according to sex, female populations have been understudied. The aim of this study was therefore to analyze the effect of...

Animal models play a pivotal role in translational neuroscience but recurrent problems in data collection, analyses , and interpretation, lack of biomarkers, and a tendency to over-reliance on mice have marred neuroscience progress, leading to one of the highest attrition rates in drug translation. Global initiatives to improve reproducibility and...

Extensive literature has reported the link between stress and tumor growth and of both with mental health. Despite the higher prevalence of affective disorders in females and the neurochemical differences according to sex, female populations have been understudied. The aim of this study was, hence, to analyze the effects of chronic social instabili...

Chronic stress has been commonly associated with mental and physical ilnesses. Different studies show a strong correlation between stress and depression and between stress and tumor development, although the underlying physiological mechanism remains unknown. Neuroendocine and neurochemical changes that occur during the inflammatory response have b...

Background: The use of animals in biomedical science remains controversial. An individual's level of concern is generally influenced by their culture, previous or current experience with animals, and the specific animal species in question. In this study we aimed to explore what people in Spain who had never or who no longer worked with laboratory...

Una emoción es un conjunto complejo de interacciones entre factores subjetivos y objetivos mediados por sistemas neurohormonales. Este conjunto de interacciones puede dar lugar a experiencias afectivas, generar procesos cognitivos relevantes, activar ajustes fisiológicos y llevar a conductas que a menudo, aunque no siempre, son adaptativas. Situaci...

Many workers contribute to the success of animal welfare and study outcomes in biomedical research. However, the professional quality of life (ProQoL) of those who work with laboratory animals has not been explored in Spain. To this end, we adapted the ProQoL scale to the Spanish population working with laboratory animals. Participants were contact...

Replacement, reduction and refinement, the 3R principles, provide a framework to minimize the use and suffering of animals in science. In this context, we aimed to determine the actual perception that individuals working with laboratory rodents in biomedical research have on animal welfare and on their interaction with the animals, as well as how t...

Supplementary data of the study Looking backward to move forward: a meta-analysis of stem cell therapy in amyotrophic lateral sclerosis.

Transplantation of several types of stem cells (SC) for the treatment of amyotrophic lateral sclerosis (ALS) has been evaluated in numerous Phase I/II clinical trials with inconclusive results. Here, we conducted a meta-analysis to systematically assess the outcome of SC therapy trials which report the evolution of each patient before and after cel...

Rearing laboratory mice in groups is important since social isolation after weaning induces brain alterations, which entails behavioral abnormalities in adulthood. Age is an important factor when grouping males of different litters due to inter-male aggressiveness. The aim of this study was to determine whether newly weaned mice could safely be gro...

Recent advances in stem cell biology and molecular engineering have improved and simplified the methodology employed to create experimental chimeras, highlighting their value in basic research and broadening the spectrum of potential applications. Experimental chimeras have been used for decades during the generation of murine genetic models, this...

There are different husbandry situations that lead to social isolation of male mice. Besides legal considerations, single housing has a negative impact on behavioural and molecular studies. We have implemented two strategies, the ‘companion mouse’ and just-weaned male grouping, to reduce the number of male mice housed singly in our facility. We hav...

Striatal-enriched protein tyrosine phosphatase (STEP) modulates key signaling molecules involved in synaptic plasticity and neuronal function. It is postulated that STEP opposes the development of long-term potentiation (LTP) and that it exerts a restraint on long-term memory (LTM). Here, we examined whether STEP61 levels are regulated during hippo...

We have generated two human induced pluripotent stem cell (iPSC) lines from CD133 ⁺ cells isolated from umbilical cord blood (CB) of a female child using non-integrative Sendai virus. Here we describe the complete characterization of these iPSC lines: PRYDi-CB5 and PRYDi-CB40.

Mutations in PINK1 (PARK6), a serine/threonine kinase involved in mitochondrial homeostasis, are associated with early onset Parkinson’s disease. Fibroblasts from Parkinson’s disease patients with compound heterozygous mutations in exon 7 (c.1488 + 1G > A; c.1252_1488del) showed no apparent signs of mitochondrial impairment. To elucidate changes pr...

INTRODUCCIÓN El material utilizado como lecho es un factor importante en la estabulación de los roedores. En este estudio hemos analizado tres diferentes materiales, el chopo, el abeto y la celulosa, y su uso como viruta para ratones de laboratorio. MATERIAL Y MÉTODOS Ratones C57BL/6J (Janvier) de 7 semanas de edad de ambos sexos se alojaron en gr...

Brain mitochondrial complex I (CI) damage is associated with the loss of the dopaminergic neurons of the Substantia Nigra in Parkinson's Disease (PD) patients. However, whether CI inhibition is associated with any alteration of the mitochondrial respiratory chain (MRC) organization in PD patients is unknown. To address this issue, here we analyzed...

A. Fingerprinting analyses of the clones used in the study and their corresponding fibroblasts; BJ: unrelated control. B. Karyotypes. C. iPSC colonies showed robust expression of pluripotent markers such as OCT4, SSEA-4 and Nanog. D. Pluripotency genes were expressed at similar levels than in control human embryonic stem cells (H9). E-F. Pluripoten...

Quantitative PCR analysis of RNA levels of mitochondrial fusion (MFN2) and fission (DNM1L and MFF) genes in neural progenitors (NP) and neurons (N) showed a significant effect of time (developmental stage) and no differences across genotypes. Two-way ANOVA; * p < 0.05 and ** < p 0.001.

A. qPCR of MFN2, DNM1L and MFF showed a decrease in mitofusin2 and an increase in fission factor in the PINK1 mutants. B. At the protein level WB analysis of MFN2 showed a small increase, suggesting that the transcriptional decrease might be compensatory to a decreased degradation, while (C) MFF protein expression was elevated. Columns represent th...

Brain-derived neurotrophic factor (BDNF) regulates synaptic strengthening and memory consolidation, and altered BDNF expression is implicated in a number of neuropsychiatric and neurodegenerative disorders. BDNF potentiates NMDAR function through activation of Fyn and ERK1/2. STriatal-Enriched protein tyrosine Phosphatase (STEP) is also implicated...

The information from nociceptors is processed in the dorsal horn of the spinal cord by complex circuits involving excitatory and inhibitory interneurons. It is well documented that GluN2B and ERK1/2 phosphorylation contribute to central sensitization. STriatal-Enriched protein tyrosine Phosphatase (STEP) dephosphorylates GluN2B and ERK1/2, promotin...

Background Lamins are the major structural proteins inside the nuclear lamina and their alterations are implicated in relatively few diseases, classified as laminopathies. In addition, lamin alterations have been described as playing a role in some neurodegenerative diseases, such as adult onset autosomal dominant leukodistrophy and Parkinson’s dis...

Levodopa-induced dyskinesias (LID) are a frequent complication of Parkinson's disease pharmacotherapy that causes significant disability and narrows the therapeutic window. Pharmacological management of LID is challenging partly because the precise molecular mechanisms are not completely understood. Here, our aim was to determine molecular changes...

L-DOPA is the most effective treatment for Parkinson's disease (PD), but prolonged use leads to disabling motor complications including dyskinesia. Strong evidence supports a role of the subthalamic nucleus (STN) in the pathophysiology of PD whereas its role in dyskinesia is a matter of controversy. Here, we investigated the involvement of STN in d...

Down syndrome, the most common genetic disorder leading to mental retardation, is caused by the presence of all or part of an extra copy of chromosome 21. At relatively early ages, Down syndrome patients develop progressive formation and extracellular aggregation of amyloid-β peptide, considered as one of the causal factors for the pathogenesis of...

Down syndrome (DS) associates with impaired brain functions, but the underlying mechanism(s) are yet unclear. The "gene dosage" hypothesis predicts that in DS, overexpression of a single gene can impair multiple brain functions through a signal amplification effect due to impaired regulatory mechanism(s). Here, we report findings attributing to imp...

BACE2 is homologous to BACE1, a beta-secretase that is involved in the amyloidogenic pathway of amyloid precursor protein (APP), and maps to the Down syndrome critical region of chromosome 21. Alzheimer disease neuropathology is common in Down syndrome patients at relatively early ages, and it has thus been speculated that BACE2 co-overexpression w...

The aim of this study was to describe the prevalence and severity of behavioural changes associated with age and their relationship to risk factors such as sex, reproductive status, bodyweight and age. A cross-sectional study design was chosen. A total of 325 geriatric dogs were included. Owners of dogs older than nine years were interviewed by a v...

Neurological deficits in the offspring caused by human maternal hypothyroxinemia are thought to be irreversible. To understand the mechanism responsible for these neurological alterations, we induced maternal hypothyroxinemia in pregnant rats. Behavior and synapse function were evaluated in the offspring of thyroid hormone-deficient rats. Our data...

The Cognitive Dysfunction syndrome is a neurodegenerative disorder which goes with changes in four categories of behaviour: sleep/wake cycles, changes in social interaction, breakdown in house training and disorientation. The aim was to value nicergoline, which increase oxygen supply to the brain, in the treatment of the syndrome. The results shown...

El Síndrome de Disfunción Cognitiva es un desorden neurodegenerativo que afecta a la capacidad cognitiva de algunos perros geriátricos. Aunque es una enfermedad poco considerada en la clínica diaria, los estudios indican que la prevalencia de este síndrome se sitúa en torno al 25%. El objetivo de este artículo es revisar los principales aspectos di...

El síndrome de Disfunción Cognitiva es una alteración neurodegenerativa que cursa con cambios en cuatro categorías de la conducta: ciclo sueño/vigilia, interacción social, hábitos higiénicos y signos de desorientación. El objetivo del estudio fue valorar la utilidad de un vasodilatador cerebral, la nicergolina, en el tratamiento del síndrome. Tras...