Harkaitz Bengoetxea

University of the Basque Country (EHU/UPV) · Department of Neuroscience

Parkinson gaixotasuna (PG) nahasmendu neurodegeneratibo motor ohikoena da, gai beltzaren zati trinkoko neurona dopaminergikoen galeragatik eta horrek eragindako mugitzeko desgaitasunagatik bereizten dena. Klinikan gehien erabiltzen diren egungo tratamenduek, hala nola lebodopak, garuneko neurotransmisio dopaminergikoa lehengoratzen dute. Hala ere,...

Curcumin is a natural polyphenol, which has a variety of pharmacological activities, including, antineoplastic, antioxidative and neuroprotective effects. Recent studies provided evidence for the bioactive role of curcumin in the prevention and treatment of various central nervous system (CNS)-related diseases including Parkinson’s, Alzheimer's, Sc...

The structure and functions of the central nervous system are influenced by environmental stimuli, which also play an important role in brain diseases. Enriched environment (EE) consists of producing modifications in the environment of standard laboratory animals to induce an improvement in their biological conditions. This paradigm promotes transc...

Major depressive disorder (MDD) is a complex illness that is arising as a growing public health concern. Although several brain areas are related to this type of disorders, at the cellular level, the parvalbumin-positive cells of the hippocampus interplay a very relevant role. They control pyramidal cell bursts, neuronal networks, basic microcircui...

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 bo...

Background and Purpose l‐DOPA prolonged treatment leads to disabling motor complications as dyskinesia that could be decreased by drugs acting on 5‐HT1A receptors. Since the internal segment of the globus pallidus, homologous to the entopeduncular nucleus in rodents, seems to be involved in the etiopathology of l‐DOPA‐induced dyskinesia, we investi...

Background and Purpose l‐DOPA‐induced dyskinesia (LID) is considered a major complication in the treatment of Parkinson's disease (PD). Buspirone (5‐HT1A partial agonist) have shown promising results in the treatment of PD and LID, however no 5‐HT‐based treatment has been approved in PD. The present study was aimed to investigate how the substantia...

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 stud...

Schizophrenia is a mental disorder characterized by psychosis, negative symptoms and cognitive impairment. Cognitive deficits are enduring and represent the most disabling symptom but are currently poorly treated. N-methyl D-aspartate receptor (NMDAR) hypofunction hypothesis has been notably successful in explaining the pathophysiological findings...

Exposure to hypobaric hypoxia at high altitude (above 2500 m asl) causes cognitive impairment, mostly attributed to changes in brain perfusion and consequently neuronal death. Enriched environment and voluntary exercise has been shown to improve cognitive function, to enhance brain microvasculature and neurogenesis, and to be neuroprotective. Here...

Several findings indicate that schizophrenia is associated with multiple abnormalities in different subtypes of interneurons, which result in a loss of inhibitory control of pyramidal cell activity. Perturbed excitatory/inhibitory balance or maladaptive disinhibition leads to cognitive impairment, a core disturbance of schizophrenia. Interneurons a...

The basal ganglia (BG), an organized network of nuclei that integrates cortical information, play a crucial role in controlling motor function. In fact, movement disorders such as Parkinson's disease (PD) and Huntington's disease (HD) are caused by the degeneration of specific structures within the BG. There is substantial evidence supporting the i...

The function of N-methyl-D-aspartate receptor (NMDAr) is critical for the processes underlying learning, memory and synaptic plasticity. The hypofunction of NMDAr is currently the most accepted hypothesis for the pathophysiology of schizophrenia. This condition is induced in animal models using NMDA antagonist drugs, such as MK801, also known as Di...

Experience of rats in a complex environment induces morphological and functional changes in the hippocampus that lead to improved cognition. N-methyl-d-aspartate receptor (NMDAR) antagonists, like MK-801, have been widely used to mimic relevant cognitive and cellular deficits of schizophrenia. However, the potential benefits of EE exposure in neuro...

Increasing evidences point to prefrontal cortex dysfunction in schizophrenia underlying cognitive disorders. Remarkable efforts are being done to understand and overcome those cognitive impairments. N-methyl D-aspartate receptor (NMDAR) hypofunction hypothesis has been notably successful to explain the pathophysiological findings and symptomatology...

Azpimarratzekoa da garunak egunerokotasunean bizitako esperientziak gorde eta portaera gidatzeko informazio hori gogorarazteko duen gaitasuna. Garuneko neurona-zirkuitu espezifikoek funtzio jakinetan parte hartzen dute, bekoki aurreko kortexa eta hipokanpoa ikasketa eta oroimen prozesuetan bereziki garrantzitsuak direlarik. Are gehiago, N-metil-D-a...

The authors found a terrible mistake in the manuscript. The legends from the Fig. 5 and 6 are interchanged. The Fig. 5 should be appeared with the legend from the Fig. 6 and Fig. 6 should be appeared with the legend from the Fig. 5.

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 strateg...

Neurotrophic factors (NTFs) are a promising therapeutic option for Parkinson’s disease (PD). They exert their function through tyrosine kinase receptors. Our goal was to assess the effects of administering a selective tyrosine kinase inhibitor (vandetanib) that blocks VEGFR2 and RET receptors in a preclinical model of PD. Rats underwent intrastriat...

Exposure to an enriched environment (EE) has neuroprotective benefits and improves recovery from brain injury due to, among other, increased neurotrophic factor expression. Through these neurotrophins, important cortical and hippocampal changes occur. Vandetanib acts as a tyrosine kinase inhibitor of cell receptors, among others, the vascular endot...

The original version of this article unfortunately contained a mistake. The name of author was changed from "Pascual Gargiulo" to "Pascual Ángel Gargiulo.

The unilateral 6-hydroxydopamine (6-OHDA) lesion of medial forebrain bundle (MFB) in rats affords us to study the advanced stages of Parkinson's disease (PD). Numerous evidences suggest synergic effects when various neurotrophic factors are administered in experimental models of PD. The aim of the present work was to assess the morphological change...

Schizophrenia is a complex psychiatric disorder with a developmental component that compromises neural circuits. Understanding the neuropathological basis of schizophrenia remains a major challenge for establishing new therapeutic approaches. In this review, causal factors for abnormal brain development in schizophrenia are discussed, with particul...

Parkinson's disease (PD) is the second most frequent neurodegenerative disorder, but current therapies are only symptomatic. Experimental models are necessary to go deeper in the comprehension of pathophysiological mechanism and to assess new therapeutic strategies. The unilateral 6-hydroxydopamine (6-OHDA) lesion either in medial forebrain bundle...

Schizophrenia is a complex psychiatric disorder with a developmental component that compromises neural circuits. Understanding the neuropathological basis of schizophrenia remains a major challenge for establishing new therapeutic approaches. Causal factors for abnormal brain development in schizophrenia include NMDA receptor hypofunction and alter...

Perinatal injections of NMDA receptor antagonist in rodents emulate some behavioral traits and neurochemical alteration of schizophrenia, like cognitive impairment and deficits in GABAergic interneuron immunoreactivity. These features are pervasive, and developing neuroprotective or neurorestorative strategies are of special interest. In this work,...

Administration of various neurotrophic factors is a promising strategy against Parkinson's disease (PD). An intrastriatal infusion of 6-hydroxidopamine (6-OHDA) in rats is a suitable model to study PD. This work aims to describe stereological parameters regarding rostro-caudal gradient, in order to characterize the model and verify its suitability...

Current research efforts are focused on the application of growth factors, such as glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor (VEGF), as neuroregenerative approaches that will prevent the neurodegenerative process in Parkinson’s disease. Continuing a previous work published by our research group, and w...

Elimination of sensory inputs (deprivation) modifies the properties of the sensory cortex and serves as a model for studying plasticity during postnatal development. Many studies on the effects of deprivation have been performed in the visual cortex using dark-rearing as a visual deprivation model. It induces changes in all cellular and molecular c...

Background / Purpose: Microvascular environment plays a fundamental role in the adaptive response to increases in activity, involving an increase in energy demand. To punctual increases in demand, the response is effected by changes in local flow, but if demand remains high, angiogenic process is triggered through the formation of new capillaries...

Background / Purpose: Postnatal development of the visual cortex is modulated by experience, especially during the critical period. Effects of vascular endothelial growth factor (VEGF) have been described in the neuronal, glial and vascular components of the neurogliovascular unit (1-3). In addition, VEGF is also involved in hippocampal-dependent...

Background / Purpose: Microvascular environment plays a fundamental role in the adaptive response to increases in activity, involving an increase in energy demand. The response to acute increases in demand is effected by changes in local flow, but if demand remains high, angiogenic process is triggered through the formation of new capillaries fro...

VEGF is the major angiogenic and vascular permeability factor in health and disease. Vascular development depends on function, and in sensory areas is experience-dependent. Our aim was to investigate, qualitatively and quantitatively, the effects of intracortical infusion and neutralisation of VEGF during the first days of the critical visual perio...

The angiogenesis process is a key event for glioma survival, malignancy and growth. The start of angiogenesis is mediated by a cascade of intratumoural events: alteration of the microvasculature network; a hypoxic microenvironment; adaptation of neoplastic cells and synthesis of pro-angiogenic factors. Due to a chaotic blood flow, a consequence of...

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 tim...

Angioneurines are a family of molecules that include vascular growth factors such as VEGF, neurotrophins such as BDNF, IGF-I, and Erythropoietin, among others. They affect both neural and vascular processes. Due to the fact that all of them act over glia, we propose the term angioglioneurins to name them. They play a key role in the neurogliovascul...

Background / Purpose: Trophic factors are crucial in CNS development and cell survival in adults. We have proposed the term “angioglioneurins” to define molecules acting on the three components of the neurogliovascular unit (1). Vascular endothelial growth factor (VEGF) is the major angiogenic and vascular permeability factor in health and diseas...

Brain postnatal development is modulated by adaptation and experience. Experience-mediated changes increase neuronal activity leading to increased metabolic demands that involve adaptive changes including ones at the microvascular network. Therefore, vascular environment plays a key role in central nervous system (CNS) development and function in h...

Background / Purpose: Microvascular environment plays a fundamental role in the adaptive response to increases in activity, involving an increase in energy demand. To compensate for increases in demand, the response is effected by changes in local flow, but if demand remains high, an angiogenic process is triggered through the formation of new ca...

Background / Purpose: The adaptive response of the microvascular environment is crucial in meeting the requirements of the increased activity. Focal increases in blood demand are followed by modifications of local flow, but if demands persist, the supply is ensured by the angiogenesis function inducing the formation of new capillaries from pre-ex...

A subpopulation of neoplastic cells with characteristics of stem cells has been described on human multiform glioblastomas. These cells play a pivotal role in tumour angiogenesis and malignancy being involved in infiltration of adjacent normal parenchyma. The named glial stem cells could be responsible for recurrences after surgery. This is due to...

Background / Purpose: Our aim is to investigate the vascular and neuronal effects of combining VEGF infusion and environmental enrichment on the visual cortex during the initial days of the critical period. Main conclusion: Results showed that the lesion produced by a cannula implantation resulted in decreased vascular, neuronal and Caspase-3...

Postnatal development of the visual cortex is modulated by experience, especially during the critical period. In rats, a stable neuronal population is only acquired after this relatively prolonged period. Vascular endothelial growth factor (VEGF) is the most important angiogenic factor and also has strong neuroprotective, neurotrophic and neurogeni...

Background / Purpose: Visual inputs deeply modulate cortical development, inducing changes in all the visual cortex components, including astrocytes which play an important role in the development, maintenance and plasticity of the cortex. Visual deprivation causes a decrease in the astroglial population, while an enriched environment increases i...

Background / Purpose: VEGF is a key angiogenic factor playing a central role in neuroprotection, neurogenesis, neurorescue and neuroregeneration. Many CNS diseases might benefit from its therapeutic use although the passage of the BBB represents a major problem when searching an accurate administration way.In our present work we have tested a nov...

Background / Purpose: Postnatal development of the visual cortex is modulated by experience especially during the critical period. In rats, this period is relatively prolonged before acquiring stable neuronal population. VEGF is the major angiogenic factor having also strong neuroprotective, neurotrophic and neurogenic properties. Similar effects...

VEGF is a major angiogenic factor and also has strong neuroprotective and neurotrophic properties in pathological conditions. The same effects have been described for rats reared in an enriched environment. The present study aims to investigate the effects on final cell population of combining enriched environment (EE) and infusion of VEGF in the v...

Brain edema in gliomas is an epiphenomenon related to blood–brain-barrier (BBB) breakdown in which endothelial nitric oxide synthase (eNOS) plays a key role. When induced by vascular endothelial growth factor (VEGF), eNOS synthesizes nitric oxide that increases vascular permeability. We investigated the relationship between eNOS, VEGF and BBB dysfu...

We investigated the effects of exogenous Vascular Endothelial Growth Factor VEGF combined with an enriched environment on BBB integrity after a minimal trauma induced during the first days of the critical visual period in rats, when peak levels of endogenous VEGF secretion are reached. VEGF was administered using osmotic mini-pumps placed in middle...

Brain edema in gliomas is an epiphenomenon related to blood–brain-barrier (BBB) breakdown in which endothelial nitric oxide synthase (eNOS) plays a key role. When induced by vascular endothelial growth factor (VEGF), eNOS synthesizes nitric oxide that increases vascular permeability. We investigated the relationship between eNOS, VEGF and BBB dysfu...

After birth, exposure to visual inputs modulates cortical development, inducing numerous changes in all of the components of the visual cortex. Most of the cortical changes thus induced occur during what is called the critical period. Astrocytes play an important role in the development, maintenance and plasticity of the cortex as well as in the st...

The development of the cortical vascular network depends on functional maturation. External inputs are an essential requirement in the modeling of the visual cortex, mainly during the critical period, when the functional and structural properties of visual cortical neurons are particularly susceptible to alterations. Vascular endothelial growth fac...

Objectives: The aim was to investigate, qualitatively and quantitatively, the regional cortical effects of intracortical infusion and neutralisation of VEGF on the light trauma induced by the implantation of an osmotic minipump during the first days of the critical visual period in rats, when peak levels of endogeneous VEGF secretion are reached. M...

The development of the cortical vascular tree depends on functional development. External inputs are an essential requirement in the modeling of the visual cortex, mainly during the critical period, when congruous blood supply is needed. The blood brain barrier (BBB) function regulates the passage of substances between the blood and the brain paren...