Analysis of age-related changes in the left ventricular myocardium with multiphoton microscopy.

Aging induces cardiac remodeling, resulting in an increase in the risk of suffering heart diseases, including heart failure. Collagen deposition increases with age and, together with sarcomeric changes in cardiomyocytes, may lead to ventricular stiffness. Multiphoton (MP) microscopy is a useful technique to visualize and detect variations in cardiac structures in a label free fashion.

Experimentally-guided in silico design of engineered heart tissues to improve cardiac electrical function after myocardial infarction.

Engineered heart tissues (EHTs) built from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) showed promising results for cardiac function restoration following myocardial infarction. Nevertheless, human iPSC-CMs have longer action potential and lower cell-to-cell coupling than adult-like CMs. These immature electrophysiological properties favor arrhythmias due to the generation of electrophysiological gradients when hiPSC-CMs are injected in the cardiac tissue.

Interindividual Age-Independent Differences in Human CX43 Impact Ventricular Arrhythmic Risk.

Connexin 43 (CX43) is one of the major components of gap junctions, the structures responsible for the intercellular communication and transmission of the electrical impulse in the left ventricle. There is limited information on the histological changes of CX43 with age and their effect on electrophysiology, especially in humans. Here, we analyzed left ventricular biopsies from living donors starting at midlife to characterize age-related CX43 remodeling.

Automatic quantification of myocardial remodeling features in human ventricular tissue from label-free microscopy.

The procedures used routinely for collagen and lipofuscin evaluation are, in many cases, qualitative, observer dependent, and disregard spatial distribution. Here, we present a protocol for automatic quantification and spatial characterization of collagen and lipofuscin from label-free microscopy images of human ventricular tissues. We describe the steps for sample collection, tissue processing, image acquisition, and quantification of collagen and lipofuscin.

Analysis of age-related left ventricular collagen remodeling in living donors: Implications in arrhythmogenesis.

Age-related fibrosis in the left ventricle (LV) has been mainly studied in animals by assessing collagen content. Using second-harmonic generation microscopy and image processing, we evaluated amount, aggregation and spatial distribution of LV collagen in young to old pigs, and middle-age and elder living donors. All collagen features increased when comparing adult and old pigs with young ones, but not when comparing adult with old pigs or middle-age with elder individuals.

Chronological and biological aging of the human left ventricular myocardium: Analysis of microRNAs contribution.

Aging is the main risk factor for cardiovascular diseases. In humans, cardiac aging remains poorly characterized. Most studies are based on chronological age (CA) and disregard biological age (BA), the actual physiological age (result of the aging rate on the organ structure and function), thus yielding potentially imperfect outcomes.

Minimally invasive system to reliably characterize ventricular electrophysiology from living donors.

Cardiac tissue slices preserve the heterogeneous structure and multicellularity of the myocardium and allow its functional characterization. However, access to human ventricular samples is scarce. We aim to demonstrate that slices from small transmural core biopsies collected from living donors during routine cardiac surgery preserve structural and functional properties of larger myocardial specimens, allowing accurate electrophysiological characterization.

Modulation of cortical slow oscillatory rhythm by GABA receptors: an in vitro experimental and computational study.

Key Points: We confirm that GABA receptors (GABA -Rs) are involved in the termination of Up-states; their blockade consistently elongates Up-states. GABA -Rs also modulate Down-states and the oscillatory cycle, thus having an impact on slow oscillation rhythm and its regularity. The most frequent effect of GABA -R blockade is elongation of Down-states and subsequent decrease of oscillatory frequency, with an increased regularity.

GABA receptors: modulation of thalamocortical dynamics and synaptic plasticity.

GABA-receptors (GABA-Rs) are metabotropic, G protein-coupled receptors for the neurotransmitter GABA. Their activation induces slow inhibitory control of the neuronal excitability mediated by pre- and postsynaptic inhibition. Presynaptically GABA-Rs reduce GABA and glutamate release inhibiting presynaptic Ca channels in both inhibitory and excitatory synapses while postsynaptic GABA-Rs induce robust slow hyperpolarization by the activation of K channels.

Altered slow (<1 Hz) and fast (beta and gamma) neocortical oscillations in the 3xTg-AD mouse model of Alzheimer's disease under anesthesia.

The 3xTg-AD mouse model reproduces the main features associated with the etiology of familial Alzheimer's disease (AD). To investigate whether these features imply functional cortical network alterations and their evolution with age, we studied spontaneous slow oscillations, activity that integrates cellular and network properties. We quantified different parameters of the emergent slow oscillations-alternating Up and Down states-and of the embedded beta-gamma rhythms of 3xTg-AD and wild-type mice at 7 and 20 months of age.

Beta and Gamma Oscillations in Prefrontal Cortex During NMDA Hypofunction: An In Vitro Model of Schizophrenia Features.

NMDA receptor (NMDAr) hypofunction has been widely used as a schizophrenia model. Decreased activation of NMDAr is associated with a disrupted excitation/inhibition balance in the prefrontal cortex and with alterations in gamma synchronization. Our aim was to investigate whether this phenomenon could be reproduced in the spontaneous oscillatory activity generated by the local prefrontal network in vitro and, if so, to explore the effects of antipsychotics on the resulting activity.

Slow and Fast Neocortical Oscillations in the Senescence-Accelerated Mouse Model SAMP8.

The senescence-accelerated mouse prone 8 (SAMP8) model is characterized by accelerated, progressive cognitive decline as well as Alzheimer's disease (AD)-like neurodegenerative changes, and resembles the etiology of multicausal, sporadic late-onset/age-related AD in humans. Our aim was to find whether these AD-like pathological features, together with the cognitive deficits present in the SAMP8 strain, are accompanied by disturbances in cortical network activity with respect to control mice (SAM resistance 1, SAMR1) and, if so, how the alterations in cortical activity progress with age. For this purpose, we characterized the extracellular spontaneous oscillatory activity in different regions of the cerebral cortex of SAMP8 and SAMR1 mice under ketamine anesthesia at 5 and 7 months of age.

Inhibitory modulation of cortical up states.

The balance between excitation and inhibition is critical in the physiology of the cerebral cortex. To understand the influence of inhibitory control on the emergent activity of the cortical network, inhibition was progressively blocked in a slice preparation that generates spontaneous rhythmic up states at a similar frequency to those occurring in vivo during slow-wave sleep or anesthesia. Progressive removal of inhibition induced a parametric shortening of up state duration and elongation of the down states, the frequency of oscillations decaying.