Efectos neurovasculares y cognitivos de la administración intracortical del VEGF y el enriquecimiento ambiental durante el desarrollo postnatal de ratas Long Evans

140 págs.[ES] El periodo crítico es la ventana temporal de máxima reorganización cortical, dando lugar a la consolidación de las conexiones sinápticas. Tanto los factores de crecimiento como la experiencia juegan un papel importante en el desarrollo postnatal. El VEGF es el principal factor implicado en la angiogénesis durante el desarrollo, y presenta efectos neuroprotectores, neurogénicos y neurotróficos. La cría en entorno enriquecido induce cambios relevantes en el desarrollo del SNC y aumenta entre otros, la expresión de neurotrofinas como el VEGF. Ambas estrategias están relacionadas con la mejora del aprendizaje. Los efectos de la administración intracortical del VEGF y de la cría en entornos enriquecidos durante el periodo crítico del sistema visual dependen del momento de aplicación y de la duración de las mismas. Mientras que la infusión intracortical durante 1 semana induce un aumento de la densidad neuronal, una administración más prolongada produce un aumento del lecho vascular. Estos cambios sólo se observan en el caso de que la implantación de la bomba osmótica haya producido un efecto negativo sobre dicho parámetro. En cambio, el entorno enriquecido induce un aumento de la densidad vascular cuando es aplicado durante 1 semana, y un aumento de la densidad neuronal en el caso de la exposición durante 4 semanas. Además, la administración intracortical del VEGF muestra un aumento de la densidad vascular del giro dentado simultáneamente de una disminución en la latencia de aprendizaje. Una disminución similar en la latencia de aprendizaje se relaciona con el aumento de la densidad neuronal debida a la cría en un entorno enriquecido. Por lo tanto, ambas estrategias muestran efectos notables sobre componentes neurovasculares y juegan un papel crucial en el aprendizaje y la memoria visuoespacial, pudiendo ser empleadas como estrategias neuroreparadoras en distintas patologías cerebrales.Tesis realizada con la beca predoctoral FPU (Formación de Profesorado Universitario) del Ministerio de Educación.Ayuda a grupos consolidados del Gobierno Vasco (IT 491-10).Fundación Jesús Gangoiti de Barrera

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)

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)

Ingurune aberastuaren eragina eskizofrenian

Eskizofrenia gure giza11eari eragiten dioten patologia psikiatriko ohikoen eta minusbaliagarrienetakoa da. Besteak beste, ikasteko zailtasunak eta oroimenaren hutsegiteak dira zailtasun garrantzitsuak gizarte-integrazioari begira. Eskizofrenia, degeneraziozko gaixotasun kronikoa da eta denboran zehar lanitzen doa, baina gaur egungo ikerketa desberdinek erakusten dute terapia-estrategia egoki batek posible egin dezakeela gaixotasuna pairatzen duten kideen integrazioa hobetzea egungo gizartean. Nahiz eta eragin handiko patologia izan , bere jatorri etiopatogenikoa ez da guztiz ezaguna, bere sorreran parte bar baitezakete hainbat eta hainbat faktore desberdinek, hala nola intlamazioak, substantzia psikoaktiboak eta batik bat neurona-zirkuitu kitzikatzaileen eta inhibitzaileen arteko desorekak garapenean zehar. Nerbio Sistema Zentralaren jaio ondorengo garapenean oso funtsezkoa da neurona kitzikatzaileek sortzen dituzten se inale aferenteen eta in terneurona GABAergikoek bideratutako zirkuitu inhibitzaileen arteko oreka. Bizimoduaren eta eskizofreniaren larritasun mailen arteko korrelazio zuzena dago, eta ikusi da sedentarismoak sintomatologia areagotzen duela. Patologia neurologikoak eta neuropsikiatrikoak aztertzeko erabiltzen diren animali modeloetan, ikusi izan da ingurune aberastua dela efektuak murri zteko ahalmena duen tresnetako bat. Ingurune aberastuak, zentzumenen erabi lera, ariketa fisikoa eta gizarte-elkarrekintza areagotzen ditu. lngurunea aberasteak ikas ahalmenen eta oroimena areagotzea eragiten ditu, bai baldintza patologikoetan, baita baldintza arruntetan ere. Halaber, aberastutako ingurunean hazitako animaliek neurogenesia, gliogenesia eta dendriten adarkatze handiago bat erakutsi dute eta horrek lagun dezake hainbat neurodegenerazio gaixotasunen efektuei aurka egiten.Eskizofreniaren ezaugarri etiopatogenikoen alderdian, garrantzi handia hartzen dute sistema sentsorialen garapenean inhibizio-zirkuituei gertatzen zaizkien eraldaketek. Hori dela eta, ingurune aberastuak eskizofreniako animali modeloetan duen eragin positiboa aztertuko dugu

Murine femur micro-computed tomography and biomechanical datasets for an ovariectomy-induced osteoporosis model

The development of new effective and safer therapies for osteoporosis, in addition to improved diagnostic and prevention strategies, represents a serious need in the scientific community. Micro-CT image-based analyses in association with biomechanical testing have become pivotal tools in identifying osteoporosis in animal models by assessment of bone microarchitecture and resistance, as well as bone strength. Here, we describe a dataset of micro-CT scans and reconstructions of 15 whole femurs and biomechanical tests on contralateral femurs from C57BL/6JOlaHsd ovariectomized (OVX), resembling human post-menopausal osteoporosis, and sham operated (sham) female mice. Data provided for each mouse include: the acquisition images (.tiff), the reconstructed images (.bmp) and an.xls file containing the maximum attenuations for each reconstructed image. Biomechanical data include an.xls file with the recorded load-displacement, a movie with the filmed test and an.xls file collecting all biomechanical results.This study was funded by Basque Country government under the ELKARTEK program No. kk-2018/00031/BC and No. kk-2019/00093/BC

Efectos neurovasculares y cognitivos de la administración intracortical del VEGF y el enriquecimiento ambiental durante el desarrollo postnatal de ratas Long Evans

140 págs.[ES] El periodo crítico es la ventana temporal de máxima reorganización cortical, dando lugar a la consolidación de las conexiones sinápticas. Tanto los factores de crecimiento como la experiencia juegan un papel importante en el desarrollo postnatal. El VEGF es el principal factor implicado en la angiogénesis durante el desarrollo, y presenta efectos neuroprotectores, neurogénicos y neurotróficos. La cría en entorno enriquecido induce cambios relevantes en el desarrollo del SNC y aumenta entre otros, la expresión de neurotrofinas como el VEGF. Ambas estrategias están relacionadas con la mejora del aprendizaje. Los efectos de la administración intracortical del VEGF y de la cría en entornos enriquecidos durante el periodo crítico del sistema visual dependen del momento de aplicación y de la duración de las mismas. Mientras que la infusión intracortical durante 1 semana induce un aumento de la densidad neuronal, una administración más prolongada produce un aumento del lecho vascular. Estos cambios sólo se observan en el caso de que la implantación de la bomba osmótica haya producido un efecto negativo sobre dicho parámetro. En cambio, el entorno enriquecido induce un aumento de la densidad vascular cuando es aplicado durante 1 semana, y un aumento de la densidad neuronal en el caso de la exposición durante 4 semanas. Además, la administración intracortical del VEGF muestra un aumento de la densidad vascular del giro dentado simultáneamente de una disminución en la latencia de aprendizaje. Una disminución similar en la latencia de aprendizaje se relaciona con el aumento de la densidad neuronal debida a la cría en un entorno enriquecido. Por lo tanto, ambas estrategias muestran efectos notables sobre componentes neurovasculares y juegan un papel crucial en el aprendizaje y la memoria visuoespacial, pudiendo ser empleadas como estrategias neuroreparadoras en distintas patologías cerebrales.Tesis realizada con la beca predoctoral FPU (Formación de Profesorado Universitario) del Ministerio de Educación.Ayuda a grupos consolidados del Gobierno Vasco (IT 491-10).Fundación Jesús Gangoiti de Barrera

Enriched and deprived sensory experience induces structural changes and rewires connectivity during the postnatal development of the brain

During postnatal development, sensory experience modulates cortical development, inducing numerous changes in all of the components of the cortex. Most of the cortical changes thus induced occur during the critical period, when the functional and structural properties of cortical neurons are particularly susceptible to alterations. Although the time course for experience-mediated sensory development is specific for each system, postnatal development acts as a whole, and if one cortical area is deprived of its normal sensory inputs during early stages, it will be reorganized by the nondeprived senses in a process of cross-modal plasticity that not only increases performance in the remaining senses when one is deprived, but also rewires the brain allowing the deprived cortex to process inputs from other senses and cortices, maintaining the modular configuration. This paper summarizes our current understanding of sensory systems development, focused specially in the visual system. It delineates sensory enhancement and sensory deprivation effects at both physiological and anatomical levels and describes the use of enriched environment as a tool to rewire loss of brain areas to enhance other active senses. Finally, strategies to apply restorative features in human-deprived senses are studied, discussing the beneficial and detrimental effects of cross-modal plasticity in prostheses and sensory substitution devices implantation