Javier Yajeya

• M.D. PhD
• Principal Investigator at University of Salamanca

Background Hippocampal synaptic plasticity disruption by amyloid‐ β (A β ) peptides is thought to be responsible for learning and memory impairments in Alzheimer's disease (AD) early stage. Failures in neuronal excitability maintenance seems to be an underlying mechanism. G‐protein‐gated inwardly‐rectifying potassium (GirK) channels control neural...

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Hippocampal synaptic plasticity disruption by amyloid‐β (Aβ) peptides + thought to be responsible for learning and memory impairments in Alzheimer's disease (AD) early stage. Failures in neuronal excitability maintenance seems to be an underlying mechanism. G‐protein‐gated inwardly rectifying potassium (GirK) channels control neural excitability by...

Using an immunohistochemical technique, we have studied the distribution of kynuneric acid (KYNA) and 3-hydroxyanthranilic acid (3-HAA) in a rat brain injury model (trauma). The study was carried out inducing a cerebral ablation of the frontal motor cortex. Two mouse monoclonal specific antibodies previously developed by our group directed against...

We previously demonstrated that the administration of GH immediately after severe motor cortex injury, in rats, followed by rehabilitation, improved the functionality of the affected limb and reexpressed nestin in the contralateral motor cortex. Here, we analyze whether these GH effects depend on a time window after the injury and on the reexpressi...

The hippocampus plays a critical role in learning and memory. Its correct performance relies on excitatory/inhibitory synaptic transmission balance. In early stages of Alzheimer’s disease (AD), neuronal hyperexcitability leads to network dysfunction observed in cortical regions such as the hippocampus. G-protein-gated potassium (GirK) channels indu...

In a single transient middle cerebral artery occlusion model of stroke and using immunohistochemical techniques, the effects of a new therapeutic approach named Gemst (a member of the Poly-L-Lysine innovative therapies) have been studied in the rat brain. The expression of inflammatory (CD45, CD11b), oxidative (NO-tryptophan, NO2-tyrosine) and indo...

Significance Disruption of neuronal dendrites causes cognitive impairment in Alzheimer’s disease (AD). Rock2, a kinase of the Rho family of proteins, is a dendrite destabilizer that accumulates in the AD brain. However, why Rock2 aberrantly aggregates, causing neuronal integrity loss, is unknown. Here, we show that Rock2 protein stability is contro...

Introduction: The available immunohistochemical techniques have documented restricted distribution of vitamins in the mammalian brain. The aim of the study was to develop a highly specific antiserum directed against pantothenic acid to explore the presence of this vitamin in the mammalian brain. Material and methods: According to ELISA tests, th...

p>Using an immunohistochemical technique, we have studied the distribution of 3-OH-anthranilic acid (3-HAA) in the rat brain. Our study was carried out in control animals and in rats in which a stroke model (single transient middle cerebral artery occlusion) was performed. A monoclonal antibody directed against 3-HAA was also developed. 3-HAA was e...

Background Patellar tendinopathy has a high prevalence rate among athletes. Different therapeutic options can be found in the current literature, but none of them has been clearly established as the gold standard. The purpose of this study is to compare, in a randomized controlled trial, the clinical efficacy of eccentric exercise combined with eit...

p>A highly specific monoclonal antibody directed against nitric oxide-tryptophan (NO-W) with good affinity (10^-9M) and specificity was developed. In the rat brain, using an indirect immunoperoxidase technique, cell bodies containing NO-W were exclusively found in the intermediate and dorsal parts of the lateral septal nucleus. No immuno...

During early stages of Alzheimer's disease (AD), synaptic dysfunction induced by toxic amyloid-β (Aβ) is present before the accumulation of histopathological hallmarks of the disease. This scenario produces impaired functioning of neuronal networks, altered patterns of synchronous activity and severe functional deficits mainly due to hyperexcitabil...

Intracellular recordings in slice preparations of the basolateral amygdala were used to test which excitatory amino acid receptors mediate the excitatory postsynaptic potentials due to stimulation of the external capsule. These recordings were also used to examine the action of muscarinic agonists on the evoked excitatory potentials. Intracellular...

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive decline, brain atrophy due to neuronal and synapse loss, and formation of two pathological lesions: extracellular amyloid plaques, composed largely of amyloid-beta peptide (Aβ), and neurofibrillary tangles formed by intracellular aggregates of hyperphosph...

Alzheimer´s disease (AD) is known to be a neurodegenerative disease manifested as an inability to form new memories. Amyloid plaques and neurofibrillary tangles, formed by deposits of amyloid-β peptide (Aβ) and microtubule-binding protein tau respectively, represent the two neuropathological hallmarks of AD. These lesions mainly accumulate in brain...

Last evidences suggest that, in Alzheimer's disease (AD) early stage, Amyloid-β (Aβ) peptide induces an imbalance between excitatory and inhibitory neurotransmission systems resulting in the functional impairment of neural networks. Such alterations are particularly important in the septohippocampal system where learning and memory processes take p...

The molecular layer of the dentate gyrus appears as the main entrance gate for information into the hippocampus, i.e., where the perforant path axons from the entorhinal cortex synapse onto the spines and dendrites of granule cells. A few dispersed neuronal somata appear intermingled in between and probably control the flow of information in this a...

Nissl staining of the rabbit hippocampal molecular layers. Eight neuronal archetypes in the hippocampal molecular layer could be identified and distinguished in animals of all different ages using Nissl staining technique (at P6, P8, P10, P12, and P14 showed), according different morphology and location of the neuronal soma. Neuron archetypes from...

In order to increase our knowledge about the distribution of vitamins in the mammalian brain, we have developed a highly specific antiserum directed against retinoic acid with good affinity (10(-8) M), as evaluated by ELISA tests. In the rat brain, no immunoreactive fibers containing retinoic acid were detected. Cell bodies containing retinoic acid...

Objetive: To investigate whether transplants of encapsulated astrocytes in alginate spheres were able to recover the deficit in motor skills produced by frontal cortex lesion, in adult rats. Material and method: Male Wistar rats were used. Behavioral test, tissue culture, astrocyte transplants and immunocytochemical and histological techniques were...

Transplants of embryonic nervous tissue ameliorate motor deficits induced by motor cortex lesions in adult animals. Restoration of lost brain functions has been recently shown in grafts of homotopic cortical origin, to be associated with a functional integration of the transplant after development of reciprocal host–graft connections. Nevertheless...

Objective: Lesions of the frontal cortex produce motor deficits which are evident at three months post-injury. The aim of this study was to investigate whether short-term rehabilitation in a critical period post-injury improves the deficit in motor ability produced by motor cortex lesions in adult rats. Additionally, we studied the expression of t...

Objective: We have previously shown the functional recovery of skilled forelimb use in rats after grafting of the frontal cortex lesion with cortical or amygdalar fetal tissue when rats were obliged to use the impaired limb. Here, we aimed to explore the effects of astrocyte grafts on the motor impairments caused by frontal cortex lesion in adult...

Primary headaches including the migraine, cluster, and tension headaches are common neurological disorders which cause pain and disability to the patients. The pathomechanism of migraine is not very well understood however, current clinical findings indicate a possible primary brain disorder due to activation of the brain and brainstem as triggers...

Lesions in specific areas of the rat motor cortex generate deficits related to fine movement performance affecting the forelimb. We have previously shown that transplants of embryonic frontal cortex ameliorate these motor deficits. Amelioration has been associated with a functional integration of the transplant due to the connections established be...

Objetive: To investigate the mechanisms by which neural transplants contribute to functional recovery of the motor disorders produced by frontal cortex damage in adult rats. Material and methods: Male Wistar rats were used, with the application of behavioral tests, electrophysiologi-cal methods and immunohistochemical and histological techniques. T...

The precision of human movements to generate skills as accurate as the exercises performed by athletes are the consequence of a long and complex learning process. These processes involve a great amount of the nervous system's structures. Electrophysiological techniques have been largely used to highlight brain functions related to the control of th...

Many factors have been implicated in the pathogenesis of migraine headache, including activation of the trigeminovascular system, dysfunction of: cerebral blood vessels, circulating vasoactive substances, mitochondrial energy metabolism, brain oxygenation and metabolism, platelet disorder, alterations in serotonin levels, low levels of brain tissue...

The medial septum/diagonal band region, which participates in learning and memory processes via its cholinergic and GABAergic projection to the hippocampus, is one of the structures affected by beta amyloid (betaA) deposition in Alzheimer's disease (AD). The acute effects of betaA (25-35 and 1-40) on action potential generation and glutamatergic sy...

Using highly specific antisera directed against conjugated d-amino acids, the distribution of d-glutamate-, d-tryptophan-, d-cysteine-, d-tyrosine- and d-methionine-immunoreactive structures in the rat brain was studied. Cell bodies containing d-glutamate, but not d-glutamate-immunoreactive fibers, were found. Perikarya containing this d-amino acid...

A basic question regarding the integrative properties of the central nervous system is how transient motor commands or brief sensory stimuli are able to evoke persistent neural changes, mainly in the form of a sustained tonic rate of action potentials. Examples of this persistent neural activity have been reported in prefrontal (Fuster, 1997) and e...

It is generally accepted that the prepositus hypoglossi (PH) nucleus is the site where horizontal eye-velocity signals are integrated into eye-position ones. However, how does this neural structure produce the sustained activity necessary for eye fixation? The generation of the neural activity responsible for eye-position signals has been studied h...

To maintain horizontal eye position on a visual target after a saccade, extraocular motoneurons need a persistent (tonic) neural activity, called "eye-position signal," generated by prepositus hypoglossi (PH) neurons. We have shown previously in vitro and in vivo that this neural activity depends, among others mechanisms, on the interplay of glutam...

The effects of beta-amyloid peptide25-35 on resting membrane potential, spontaneous and evoked action potential and synaptic activity have been studied in basolateral amygdaloid complex on slices obtained from adult rats. Intracellular recordings reveal that perfusion with beta-amyloid peptide25-35 at concentrations of 400 nM and less did not gener...

An exciting topic regarding integrative properties of the nervous system is how transient motor commands or brief sensory stimuli are able to evoke persistent neuronal changes, mainly as a sustained, tonic action potential firing. A persisting firing seems to be necessary for postural maintenance after a previous movement. We have studied in vitro...

We have studied in vitro and in vivo the origin of the persistent neuronal activity underlying eye positions of fixation after eye saccades in the horizontal plane. It is proposed that the tonic firing presented by prepositus hypoglossi neurons during eye fixations is the result of the combined action of eye-velocity signals arriving from excitator...

Primary peptidergic sensory neurons of the trigeminal ganglion that innervate the cerebral dura have been involved in the pathogenesis of headache, including the migraine. In addition, it is known that nociceptive central processes of the trigeminal neurons terminate in the caudal trigeminal nucleus. Moreover, the electrical stimulation of the trig...

Cisplatin-bile acid derivatives belonging to the Bamet-family maintain both liver organotropism and cytostatic activity. "In vivo" toxicity and usefulness as chemotherapeutic agent versus liver tumors of a novel drug, Bamet-UD2 [cis-diamminechlorocholylglycinate platinum (II)], with enhanced "in vitro" cytostatic activity was investigated. Using or...

The long-term effect of transplanting embryonic frontal cortex into a unilateral frontal cortex lesion has been studied in adult rats. Before surgery, activity in an open field, muscular strength of both forelimbs, and performance in a paw-reaching-for-food task were scored in 26 rats. In 21 animals a unilateral cortex lesion was then made in the f...

Primary trigeminal neurons of the trigeminal ganglion (TG) innervate major parts of the face and head, including the dura. Electrical stimulation of the TG at specific parameters, can activate its nociceptive neurons and may serve as an experimental pain model. Markowitz [J. Neurosci. 7 (1987) 4129] reported that electrical stimulation of the trige...

Intracellular recordings in slice preparations of the basolateral amygdala were used to test which excitatory amino acid receptors mediate the excitatory postsynaptic potentials due to stimulation of the external capsule. These recordings were also used to examine the action of muscarinic agonists on the evoked excitatory potentials. Intracellular...

The central terminals of the primary sensory trigeminal ganglion (TG) neurons projecting into the caudal trigeminal nucleus (CTN) of the rat exhibit neurokinin A (NKA)-, substance P (SP)-, and calcitonin gene-related peptide (CGRP)-immunoreactivities (IRs). We stimulated the TG in the rat to induce some of the alterations which might occur during m...

In order to induce some of the alterations that occur during migraine attacks, the rat trigeminal ganglion was electrically and unilaterally stimulated for 5-30 minutes to ascertain the changes in distribution of the neuropeptides substance P, neuroklnin A and calcitonin gene-related peptide occurring in the caudal trigeminal nucleus. Following sti...

We have carried out an immunohistochemical study on the presence of neurokinin A (NKA) and substance P (SP) in the rat caudal trigeminal nucleus (CTN) after electrical stimulation of the trigeminal ganglion (TG), used as an experimental model to induce alterations, some of which may occur during migraine attacks (release of vasoactive peptides from...

In the present study, a cationic membrane conductance activated by the acetylcholine agonist carbachol was characterized in vitro in neurons of the basolateral amygdala. Extracellular perfusion of the K+ channel blockers Ba2+ and Cs+ or loading of cells with cesium acetate did not affect the carbachol-induced depolarization. Similarly, superfusion...

Two human neural cell lines were examined after intracerebral transplantation in nonimmunosuppressed adult rats. BE(2)-M17 neuroblastoma cells or NT2 teratocarcinoma cells genetically modified with the tyrosine hydroxylase (TH) gene were transplanted into four brain regions: neocortex, cerebellum, striatum and amygdala. The survival and proliferati...

The electrophysiological properties, the response to cholinergic agonists and the morphological characteristics of neurons of the basolateral complex were investigated in rat amygdala slices. We have defined three types of cells according to the morphological characteristics and the response to depolarizing pulses. Sixty-six of the recorded cells (...

The prefrontal cortex is involved in many processes, some of which are related to motor activity such eye movements and speech. Experimental data exist that suggest that prefrontal cortical activity occurs in relation to attention, short-term memory, affective discrimination, and complex forms of motor behaviour, i.e. anticipatory preparation, moto...

Single unit activity was recorded in the basolateral amygdaloid nucleus in two series of rats. In the first series, activity was recorded under control conditions and 1 minute and 24 hours after the application of a foot-shock. In the second series, activity was recorded in control conditions, during a low intensity flash stimulation and 1 minute l...

Lesion studies have shown that the functional integrity of prefrontal and posterior parietal cortex is necessary for complex behavioural performance. Recordings were made from 137 prefrontal cells in awake cats. Parietal cortex stimulation affected fifty-four cells (39.5%); thirty-four (63%) increased and twenty (37%) decreased their discharge freq...

Single unit activity was recorded in the basolateral nucleus of amygdala in rats in a passive avoidance test. Simultaneously, visual control of exploratory behaviour was carried out. Prior to establishing the conditioning, the mean frequency of the unit discharge was 14 Hz (SD = 9) and 1 minute after conditioning this unit activity decreased to val...

The effects of cooling posterior parietal cortex (areas 5 and 7) on behavior and on the activity of prefrontal neurons were assessed in monkeys performing two visual discrimination tasks with delayed choice. In both tasks, the visual cue for each trial was displayed for 0.5 s by rear projection through colored filters on a central 2.5-cm translucid...

Acute experiments were performed on anaesthetized rats using standard techniques of electrical stimulation and single-unit recording in order to study the responses of the bed nucleus of the stria terminalis (BNST) neurons to homo- and contralateral stria terminalis (ST) inputs. Satisfactory records were obtained from 174 BNST neurons. The majority...

The activity of 294 single units was recorded from the dorsolateral prefrontal cortex of monkeys performing two visual discrimination tasks with delayed response. One task, delayed matching-to-sample (DMS), required memory of a colored cue for later (18 s) matching and choice of color; the cue did not connote the location of the delayed response. T...

Rhesus monkeys were trained to perform two visual discrimination tasks with delayed response. In both tasks, the response depended on the color of the cue, a lighted circle in the center of a panel. Red and green guided one task, yellow and blue the other. In the course of performance, a fifth color (violet), non-relevant and inconsequential, was p...

The commissural component of the stria terminalis (S. T.) was studied in Equi-Thesin (92.7 mg/kg) anesthetized rats after their exposure in the caudothalamic surface of both hemispheres. Two types of connection between right and left S. T. across the anterior commissure are described: A "direct" connection set up by fibres that run through the S. T...

Intravenous infusion of angiotensin II into the cat (4.13 microng/45 min) produces a decrease of plasmatic renin activity. This reduction was not modified after the bilateral denervation of the kidneys or section of both carotid and aortic nerves. The reserpinization of the cats does not modify the angiotensin effects on the renin plasmatic concent...

Variations in the discharge of baroreceptor units in the left aortic nerve were investigated during stimulation of the stellate ganglion both in the intact cat and in vitro perfusion of the aortic arch. The effects of stimulation of the peripheral cervical sympathetic trunk of the baroreceptor discharge in the carotid nerve during in vitro perfusio...