César Venero

• PhD
• Professor (Associate) at National University of Distance Education

Social isolation in adulthood is a psychosocial stressor that can result in endocrinological and behavioral alterations in different species. In rodents, controversial results have been obtained in fear conditioning after social isolation at adulthood, while neural substrates underlying these differences are largely unknown. Neural cell adhesion mo...

Author Summary The human brain contains trillions of neuronal connections, called synapses, whose pattern of activity controls all our cognitive functions. These synaptic connections are dynamic and constantly changing in their strength and properties, and this process of synaptic plasticity is essential for learning and memory. Alterations in syna...

The transcriptional properties of unliganded thyroid hormone receptors are thought to cause the misdevelopment during hypothyroidism of several functions essential for adult life. To specifically determine the role of unliganded thyroid hormone receptor alpha1 (TRalpha1) in neuronal tissues, we introduced a mutation into the mouse TRalpha1 gene tha...

Memory formation has been associated with structural and functional modifications of synapses. Cell adhesion molecules are prominent modulators of synaptic plasticity. Here, we investigated the involvement of the cell adhesion molecules, NCAM, its polysialylated state (PSA-NCAM) and L1 in spatial learning-induced synaptic remodeling and memory stor...

Tachykinin receptor 3 (TACR3) is a member of the tachykinin receptor family and falls within the rhodopsin subfamily. As a G protein-coupled receptor, it responds to neurokinin B (NKB), its high-affinity ligand. Dysfunctional TACR3 has been associated with pubertal failure and anxiety, yet the mechanisms underlying this remain unclear. Hence, we ha...

[This corrects the article DOI: 10.1371/journal.pone.0283169.].

Introduction The main objective of the study will be to evaluate the effects of two widely used standardized mindfulness-based programs [Mindfulness-Based Stress Reduction (MBSR) and Compassion Cultivation Training (CCT)], on epigenetic, neurobiological, psychological, and physiological variables. Methods The programs will be offered in an intensi...

Introduction Loneliness is a distressful feeling that can affect mental and physical health, particularly among older adults. Cortisol, the primary hormone of the Hypothalamic-Pituitary-Adrenal axis (HPA-axis), may act as a biological transducer through which loneliness affects health. While most previous studies have evaluated the association betw...

Introduction Prolonged social isolation is a form of passive chronic stress that has consequences on human and animal behavior. The present study was undertaken to elucidate whether the long-term isolation would precipitate age-related changes in anxiety and spatial learning and memory in degus. Methods We investigated the effects of long-term soc...

The accumulation of relatively higher dose of zinc oxide nanoparticles in brain was reported to produce neurotoxicity. Indeed, nanoparticles have a high ability to penetrate biological membranes and be uptaken by cells, which may cause cell disorders and physiological dysfunctions. The aim of the current study was to evaluate, whether oral administ...

In this work, we tested the hypothesis that the development of dementia in individuals with type 2 diabetes (T2DM) requires a genetic background of predisposition to neurodegenerative disease. As a proof of concept, we induced T2DM in middle-aged hAPP NL/F mice, a preclinical model of Alzheimer's disease. We show that T2DM produces more severe beha...

Introduction The main objective of the study will be to evaluate the effects of two widely used standardized mindfulness-based programs [Mindfulness-Based Stress Reduction (MBSR) and Compassion Cultivation Training (CCT)], on epigenetic, neurobiological, psychological, and physiological variables. Methods The programs will be offered in an intensi...

It is widely accepted that some types of learning involve structural and functional changes of hippocampal synapses. Cell adhesion molecules neural cell adhesion molecule (NCAM), its polysialylated form polysialic acid to NCAM (PSA-NCAM), and L1 are prominent modulators of those changes. On the other hand, trace eyeblink conditioning, an associativ...

Aging is associated with a decline in cognitive abilities, mainly in memory and executive functioning. A similar but premature deterioration in cognitive capacities is the hallmark of mild cognitive impairment, Alzeimer’s disease and dementia. The biochemical mechanisms that cause these neurodegenerative disorders are poorly understood. However, so...

A significant number of individuals with type 2 diabetes (T2DM) develop cognitive deficits over time that in some cases could lead to dementia. It remains to be identified the diabetes-related factors or comorbid conditions that drive the association and how they work. In this manuscript, we show that 14-15 month-old hAPP NL/F mice, a knock‐in mous...

Exposure to certain environmental factors and xenobiotic agents can lead to an excess of reactive oxygen species and free radical formation that can damage neuronal cells and affect cognitive function. Silica nanoparticles, as probes for genes or proteins, are already used in nanomedicine as a nanocarrier for several drugs. In the present study, Si...

The coronavirus disease 2019 (COVID-19) pandemic led to various government-imposed limitations on social interaction and strict home confinement. Such involuntary social-distancing policies can exacerbate feelings of loneliness and alter emotional well-being. Dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) axis is a potential mecha...

Aim: The Memory Failures of Everyday (MFE) is a widely used instrument for assessing memory failure. The aim of the study was to analyze the MFE items using the Rasch model in a sample of cognitively older adults in Spain. Methods: A cross-sectional validation study in a sample of 214 healthy people aged ≥60 years who used centers for older peop...

Research in psychology and social neuroscience distinguishes between dispositional and situational empathy for the cognitive and affective aspects of empathy. Yet, the Pictorial Empathy Test (PET) is one of the few brief tests focusing on situational affective empathy. This paper describes the adaptation of PET in a two-stage process, consisting of...

Objective: This study aimed to generate updated normative data for commonly used tests in neuropsychological assessment applied to older monolingual Spanish-speaking adults: Verbal fluency tests, the Trail Making Test (TMT), and the Rey-Osterrieth complex figure test (ROCF). Method: To obtain normative data, 382 cognitively healthy 60- to 90-yea...

The aim of this study was to establish normative data for the Spanish version of the California Verbal Learning Test, the Test de Aprendizaje Verbal España-Complutense (TAVEC). Through different subtests, the TAVEC allows verbal learning and episodic memory to be evaluated, an assessment that was carried out on a sample of 382 cognitive healthy Spa...

There are important individual differences in adaptation and reactivity to stressful challenges. Being subjected to strict social confinement is a distressful psychological experience leading to reduced emotional well-being, but it is not known how it can affect the cognitive and empathic tendencies of different individuals. Cortisol, a key glucoco...

Cortisol is a glucocorticoid hormone secreted by the adrenal cortex upon the activation of the hypothalamic-pituitary-adrenal (HPA) axis. Assessment of cortisol in saliva has emerged as a reliable way of evaluating HPA function. We examined the relationships between salivary cortisol levels with both craving and cognitive performance, as a possible...

The prefrontal cortex, and especially the Dorsolateral Prefrontal Cortex (DLPFC), plays an inhibitory role in the regulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis under stressful situations. Moreover, recent evidence suggests that a sustained DLPFC activation is associated with adaptive stress regulation in anticipation of a stressful ev...

Cognitive decline is one of the hallmarks of aging and can vary from mild cognitive impairment to dementia to Alzheimer's disease. In addition to some lifestyle interventions, there is room for the use of nutraceuticals/functional foods as pharma-nutritional tools to lessen the burden of cognitive decline before it worsens. We previously reported t...

The main objetive was to analyze the accuracy of different verbal fluency tests (VFTs) in discriminating cognitively healthy subjects from individuals with mild cognitive impairment (MCI) and probable Alzheimer’s disease (AD) in a cohort of older Spanish speaking adults. As a result, we aimed to identify the VFT that best predicts conversion from M...

Phosphatase and tensin homolog on chromosome 10 (PTEN) is a tumor suppressor and autism-associated gene that exerts an important influence over neuronal structure and function during development. In addition, it participates in synaptic plasticity processes in adulthood. As an attempt to assess synaptic and developmental mechanisms by which PTEN ca...

Social isolation predominantly occurs in elderly people and it is strongly associated with cognitive decline. However, the mechanisms that produce isolation-related cognitive dysfunction during aging remain unclear. Here, we evaluated the cognitive, electrophysiological, and morphological effects of short- (4 weeks) and long-term (12 weeks) social...

Neuropathic lysosomal storage disorders (LSDs) present with activated pro-inflammatory microglia. However, anti-inflammatory treatment failed to improve disease pathology. We characterise the mechanisms underlying microglia activation in Niemann–Pick disease type A (NPA). We establish that an NPA patient and the acid sphingomyelinase knockout (ASMk...

Impaired glucose metabolism and mitochondrial decay greatly increase with age, when cognitive decline becomes rampant. No pharmacological or dietary intervention has proven effective, but proper diet and lifestyle do postpone the onset of neurodegeneration and some nutrients are being investigated. We studied insulin signaling, mitochondrial activi...

The increasing incidence of age-induced cognitive decline justifies the search for complementary ways of prevention or delay. We studied the effects of concentrates of phospholipids, sphingolipids, and/or 3-n fatty acids on the expression of genes or miRNAs related to synaptic activity and/or neurodegeneration, in the hippocampus of aged Wistar rat...

As the conceptual, methodological, and technological advances applied to dementias have evolved the construct of mild cognitive impairment (MCI), one problem encountered has been its classification into subtypes. Here, we aim to revise the concept of MCI and its subtypes, addressing the problems of classification not only from the psychometric poin...

A euthyroid state in the brain is crucial for its adequate development and function. Impairments in thyroid hormones (THs; T3 or 3,5,3′-triiodothyronine and T4 or thyroxine) levels and availability in brain can lead to neurological alterations and to psychiatric disorders, particularly mood disorders. The thyroid gland synthetizes mainly T4, which...

Cognitive capacities decline with age, an event accompanied by the altered transcription of synaptic plasticity genes. Here, we show that the transcriptional induction of Bdnf by a mnemonic stimulus is impaired in aged hippocampal neurons. Mechanistically, this defect is due to reduced NMDA receptor (NMDAR)-mediated activation of CaMKII. Decreased...

Post-traumatic stress disorder (PTSD) occurs after exposure to traumatic situations and it is characterized by cognitive deficits that include impaired explicit memory. The neurobiological bases of such PTSD-associated memory alterations are yet to be elucidated and no satisfactory treatment for them exists. To address this issue, we first studied...

Dyshomeostasis of amyloid-β peptide (Aβ) is responsible for synaptic malfunctions leading to cognitive deficits ranging from mild impairment to full-blown dementia in Alzheimer's disease. Aβ appears to skew synaptic plasticity events toward depression. We found that inhibition of PTEN, a lipid phosphatase that is essential to long-term depression,...

The term "cognitive enhancement" is currently associated with a wide range of existing, emerging, and visionary biomedical technologies that intend to improve the cognitive status of animals and human beings. As such, it offers the promise (or threat) of drastically changing the lives of citizens. Among the technologies proposed for use in humans a...

Most neuropsychiatric disorders produce cognitive deficits, sometimes representing core features of the illness. Thus, memory is the main cognitive domain disturbed in Alzheimer's disease, whereas attention is principally affected in patients with attention deficit hyperactivity disorder (ADHD). In other neuropsychiatric diseases such as schizophre...

Cognitive Enhancement: Pharmacologic, Environmental and Genetic Factors addresses the gap that exists in research on the topic, gathering multidisciplinary knowledge and tools that help the reader understand the basics of cognitive enhancement. It also provides assistance in designing procedures and pharmacological approaches to further the use of...

Fluoxetine (FLX) is prescribed to treat depression and anxiety in adolescent patients. However, FLX has anxiogenic effects during the acute phase of treatment, and caution has been raised due to increased suicidal thinking and behavior. Herein, we sought to study in adolescent (35-day-old) male rats, the effects of short-term FLX treatment (10 mg/k...

. Patients with dementia, especially Alzheimer’s disease, present several circadian impairments related to an accelerated perturbation of their biological clock that is caused by the illness itself and not merely age-related. Thus, the objective of this work was to elucidate whether these circadian system alterations were already present in patient...

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Cognitive decline is one of the many characteristics of aging. Reduced long-term potentiation (LTP) and long-term depression (LTD) are thought to be responsible for this decline, although the precise mechanisms underlying LTP and LTD dampening in the old remain unclear. We previously showed that aging is accompanied by the loss of cholesterol from...

Cognitive decline is one of the many characteristics of aging. Reduced long-term potentiation (LTP) and long-term depression (LTD) are thought to be responsible for this decline, although the precise mechanisms underlying LTP and LTD dampening in the old remain unclear. We previously showed that aging is accompanied by the loss of cholesterol from...

The adaptive response to physical or psychological challenges or threats involves the modulation of the three regulatory systems: the nervous, endocrine and immune systems. Correct communication between these systems is required to maintain a homeostatic balance, and to guarantee the health and survival of the individual. While the stress response...

Effects of FGL on passive membrane properties of CA1 hippocampal neurons. (A–B) Application of FGL to cultured hippocampal slices did not alter input resistance (a) or holding current (b) when compared with untreated control neurons. N, number of cells. (TIF)

FGL alters NMDAR decay kinetics in a PKC-independent manner. Organotypic slice cultures were treated with FGL (with or without chelerythrine) for 24 h and then transferred to fresh culture medium for an additional 24 h prior to recordings. Control slices were kept in regular culture medium until the recordings. NMDAR-mediated synaptic responses wer...

FGL does not alter structural plasticity of dendritic spines. (A) Representative confocal fluorescence image of dendritic spines expressing actin-GFP before (0′) or at different times after induction of LTP (5′, 20′) from untreated or FGL-treated organotypic slices. Spine heads undergoing plasticity are marked with arrows. LTP was induced using a s...

Chelerythrine inhibition of PKC activity on MARCKS (Myristoylated Alanine-Rich C-Kinase Substrate). (A) Left panels. Representative confocal images of BHK cells transfected with GFP-MARCKS under basal conditions (“no treatment”) or 20 s after application of the PKC activator 12-O-tetradecanoylphorbol-13-acetate (“TPA,” 0.1 µM). Right panels. Simila...

FGL does not alter long-term synaptic depression. Organotypic slice cultures were treated with FGL for 24 h and then transferred to fresh culture medium (without FGL) for an additional 24 h prior to recordings. Control slices were kept in regular culture medium until the recordings. LTD was induced by pairing presynaptic 1 Hz stimulation (300 pulse...

Unaltered spine neck length after FGL treatment. (A) Representative confocal projection image of CA1 pyramidal neurons. Bar = 150 µm. (B) Representative high magnification confocal projection image of apical dendrites to illustrate dendritic spines. Bar = 1.5 µm. (C) Quantification of spine neck length measured three-dimensionally. N, number of rat...

Spatial learning in the Morris water maze is altered by MEK and PI3K inhibitors. Mean distances traveled to find the hidden platform in the Morris water maze over the 2 training days (four trials each). N, number of animals. Rats injected with vehicle, FGL (20 µg), PD98059 (MEK inhibitor, 20 nmol), or LY294002 (PI3K inhibitor, 4.5 nmol), as indicat...

Additional experimental procedures are described in this supplementary text. (DOCX)

FGL facilitates LTP in CA1 neurons. Cumulative frequency distribution of EPSC fold potentiation from the individual LTP experiments plotted in Figure 6D–E. Data are presented for control slices or slices treated with FGL, chelerythrine, or FGL plus chelerythrine, as indicated. (TIF)

PKC inhibition does not alter spatial learning. Mean distances swam to find the hidden platform in the Morris water maze from vehicle- (white column) and PKC inhibitor-treated rats (gray columns; A, chelerythrine; B, GF109203X), over the eight training trials (four trials per day). N, the number of animals. (TIF)

Hypothyroidism is the most common hormonal disease in adults, which is frequently accompanied by learning and memory impairments and emotional disorders. However, the deleterious effects of thyroid hormones deficiency on emotional memory are poorly understood and often underestimated. To evaluate the consequences of hypothyroidism on emotional lear...

The key roles played by the neural cell adhesion molecule (NCAM) in plasticity and cognition underscore this membrane protein as a relevant target to develop cognitive-enhancing drugs. However, NCAM is a structurally and functionally complex molecule with multiple domains engaged in a variety of actions, which raise the question as to which NCAM fr...

Chronic orofacial pain encompasses a range of debilitating conditions, however in contrast to other body regions, few animal models are available to investigate mechanisms and treatments in the trigeminal area. Particularly, there is a lack of reliable models and testing methods in mice. We have behaviourally tested C57BL/6 mice subjected to unilat...

Patients with Alzheimer's disease (AD) suffer from impaired memory and emotional disturbances, the pathogenesis of which is not entirely clear. In APP/PS1 transgenic mice, a model of AD in which amyloid β (Aβ) accumulates in the brain, we have examined neurons in the lateral nucleus of the amygdala (LA), a brain region crucial to establish cued fea...

In this study, we examined whether chronic stress in adulthood can exert long-term effects on spatial-cognitive abilities and on the survival of newborn hippocampal cells in aging animals. Male Wistar rats were subjected to chronic unpredictable stress at midlife (12 months old) and then reexposed each week to a stress stimulus. When evaluated in t...

The neural cell adhesion molecule (NCAM) plays a pivotal role in neural development, regeneration, synaptic plasticity, and memory processes. P2 is a 12-amino-acid peptide derived from the second immunoglobulin-like (Ig) module of NCAM mediating cis-homophilic interactions between NCAM molecules present on the same cell. P2 is a potent NCAM agonist...

The role of the hippocampus in pavlovian fear conditioning is controversial. Although lesion and pharmacological inactivation studies have suggested a key role for the dorsal hippocampus in contextual fear conditioning, the involvement of the ventral part is still uncertain. Likewise, the debate is open with regard to the putative implication of ea...