Variations in cochlea shape reveal different evolutionary adaptations in primates and rodents.

The presence of a coiled cochlea is a unique feature of the therian inner ear. While some aspects of the cochlea are already known to affect hearing capacities, the full extent of the relationships between the morphology and function of this organ are not yet understood-especially when the effect of body size differences between species is minimized. Here, focusing on Euarchontoglires, we explore cochlear morphology of 33 species of therian mammals with a restricted body size range. Using µCT scans, 3D models and 3D geometric morphometrics, we obtained shape information of the cochlea and used it to build phylogenetically corrected least square models with 12 hearing variables obtained from the literature. Our results reveal that different taxonomic groups differ significantly in cochlea shape. We further show that these shape differences are related to differences in hearing capacities between these groups, despite of similar cochlear lengths. Most strikingly, rodents with good low-frequency hearing display "tower-shaped" cochleae, achieved by increasing the degree of coiling of their cochlea. In contrast, primates present relatively wider cochleae and relative better high frequency hearing. These results suggest that primates and rodents increased their cochlea lengths through different morpho-evolutionary trajectories.

Image dataset for benchmarking automated fish detection and classification algorithms.

Multiparametric video-cabled marine observatories are becoming strategic to monitor remotely and in real-time the marine ecosystem. Those platforms can achieve continuous, high-frequency and long-lasting image data sets that require automation in order to extract biological time series. The OBSEA, located at 4 km from Vilanova i la Geltrú at 20 m depth, was used to produce coastal fish time series continuously over the 24-h during 2013-2014. The image content of the photos was extracted via tagging, resulting in 69917 fish tags of 30 taxa identified. We also provided a meteorological and oceanographic dataset filtered by a quality control procedure to define real-world conditions affecting image quality. The tagged fish dataset can be of great importance to develop Artificial Intelligence routines for the automated identification and classification of fishes in extensive time-lapse image sets.

Towards Naples Ecological REsearch for Augmented Observatories (NEREA): The NEREA-Fix Module, a Stand-Alone Platform for Long-Term Deep-Sea Ecosystem Monitoring.

Deep-sea ecological monitoring is increasingly recognized as indispensable for the comprehension of the largest biome on Earth, but at the same time it is subjected to growing human impacts for the exploitation of biotic and abiotic resources. Here, we present the Naples Ecological REsearch (NEREA) stand-alone observatory concept (NEREA-fix), an integrated observatory with a modular, adaptive structure, characterized by a multiparametric video-platform to be deployed in the Dohrn canyon (Gulf of Naples, Tyrrhenian Sea) at ca. 650 m depth. The observatory integrates a seabed platform with optoacoustic and oceanographic/geochemical sensors connected to a surface transmission buoy, plus a mooring line (also equipped with depth-staged environmental sensors). This reinforced high-frequency and long-lasting ecological monitoring will integrate the historical data conducted over 40 years for the Long-Term Ecological Research (LTER) at the station "Mare Chiara", and ongoing vessel-assisted plankton (and future environmental DNA-eDNA) sampling. NEREA aims at expanding the observational capacity in a key area of the Mediterranean Sea, representing a first step towards the establishment of a bentho-pelagic network to enforce an end-to-end transdisciplinary approach for the monitoring of marine ecosystems across a wide range of animal sizes (from bacteria to megafauna).

The Hierarchic Treatment of Marine Ecological Information from Spatial Networks of Benthic Platforms.

Measuring biodiversity simultaneously in different locations, at different temporal scales, and over wide spatial scales is of strategic importance for the improvement of our understanding of the functioning of marine ecosystems and for the conservation of their biodiversity. Monitoring networks of cabled observatories, along with other docked autonomous systems (e.g., Remotely Operated Vehicles [ROVs], Autonomous Underwater Vehicles [AUVs], and crawlers), are being conceived and established at a spatial scale capable of tracking energy fluxes across benthic and pelagic compartments, as well as across geographic ecotones. At the same time, optoacoustic imaging is sustaining an unprecedented expansion in marine ecological monitoring, enabling the acquisition of new biological and environmental data at an appropriate spatiotemporal scale. At this stage, one of the main problems for an effective application of these technologies is the processing, storage, and treatment of the acquired complex ecological information. Here, we provide a conceptual overview on the technological developments in the multiparametric generation, storage, and automated hierarchic treatment of biological and environmental information required to capture the spatiotemporal complexity of a marine ecosystem. In doing so, we present a pipeline of ecological data acquisition and processing in different steps and prone to automation. We also give an example of population biomass, community richness and biodiversity data computation (as indicators for ecosystem functionality) with an Internet Operated Vehicle (a mobile crawler). Finally, we discuss the software requirements for that automated data processing at the level of cyber-infrastructures with sensor calibration and control, data banking, and ingestion into large data portals.

New High-Tech Flexible Networks for the Monitoring of Deep-Sea Ecosystems.

Increasing interest in the acquisition of biotic and abiotic resources from within the deep sea (e.g., fisheries, oil-gas extraction, and mining) urgently imposes the development of novel monitoring technologies, beyond the traditional vessel-assisted, time-consuming, high-cost sampling surveys. The implementation of permanent networks of seabed and water-column-cabled (fixed) and docked mobile platforms is presently enforced, to cooperatively measure biological features and environmental (physicochemical) parameters. Video and acoustic (i.e., optoacoustic) imaging are becoming central approaches for studying benthic fauna (e.g., quantifying species presence, behavior, and trophic interactions) in a remote, continuous, and prolonged fashion. Imaging is also being complemented by in situ environmental-DNA sequencing technologies, allowing the traceability of a wide range of organisms (including prokaryotes) beyond the reach of optoacoustic tools. Here, we describe the different fixed and mobile platforms of those benthic and pelagic monitoring networks, proposing at the same time an innovative roadmap for the automated computing of hierarchical ecological information on deep-sea ecosystems (i.e., from single species' abundance and life traits to community composition, and overall biodiversity).

Real-Time Seismic Data from the Bottom Sea.

An anchored marine seismometer, acquiring real-time seismic data, has been built and tested. The system consists of an underwater seismometer, a surface buoy, and a mooring line that connects them. Inductive communication through the mooring line provides an inexpensive, reliable, and flexible solution. Prior to the deployment the dynamics of the system have been simulated numerically in order to find optimal materials, cables, buoys, and connections under critical marine conditions. The seismometer used is a high sensitivity triaxial broadband geophone able to measure low vibrational signals produced by the underwater seismic events. The power to operate the surface buoy is provided by solar panels. Additional batteries are needed for the underwater unit. In this paper we also present the first results and an earthquake detection of a prototype system that demonstrates the feasibility of this concept. The seismometer transmits continuous data at a rate of 1000 bps to a controller equipped with a radio link in the surface buoy. A GPS receiver on the surface buoy has been configured to perform accurate timestamps on the seismic data, which makes it possible to integrate the seismic data from these marine seismometers into the existing seismic network.

New Vectorial Propulsion System and Trajectory Control Designs for Improved AUV Mission Autonomy.

Autonomous Underwater Vehicles (AUV) are proving to be a promising platform design for multidisciplinary autonomous operability with a wide range of applications in marine ecology and geoscience. Here, two novel contributions towards increasing the autonomous navigation capability of a new AUV prototype (the Guanay II) as a mix between a propelled vehicle and a glider are presented. Firstly, a vectorial propulsion system has been designed to provide full vehicle maneuverability in both horizontal and vertical planes. Furthermore, two controllers have been designed, based on fuzzy controls, to provide the vehicle with autonomous navigation capabilities. Due to the decoupled system propriety, the controllers in the horizontal plane have been designed separately from the vertical plane. This class of non-linear controllers has been used to interpret linguistic laws into different zones of functionality. This method provided good performance, used as interpolation between different rules or linear controls. Both improvements have been validated through simulations and field tests, displaying good performance results. Finally, the conclusion of this work is that the Guanay II AUV has a solid controller to perform autonomous navigation and carry out vertical immersions.

Middleware for Plug and Play Integration of Heterogeneous Sensor Resources into the Sensor Web.

The study of global phenomena requires the combination of a considerable amount of data coming from different sources, acquired by different observation platforms and managed by institutions working in different scientific fields. Merging this data to provide extensive and complete data sets to monitor the long-term, global changes of our oceans is a major challenge. The data acquisition and data archival procedures usually vary significantly depending on the acquisition platform. This lack of standardization ultimately leads to information silos, preventing the data to be effectively shared across different scientific communities. In the past years, important steps have been taken in order to improve both standardization and interoperability, such as the Open Geospatial Consortium's Sensor Web Enablement (SWE) framework. Within this framework, standardized models and interfaces to archive, access and visualize the data from heterogeneous sensor resources have been proposed. However, due to the wide variety of software and hardware architectures presented by marine sensors and marine observation platforms, there is still a lack of uniform procedures to integrate sensors into existing SWE-based data infrastructures. In this work, a framework aimed to enable sensor plug and play integration into existing SWE-based data infrastructures is presented. First, an analysis of the operations required to automatically identify, configure and operate a sensor are analysed. Then, the metadata required for these operations is structured in a standard way. Afterwards, a modular, plug and play, SWE-based acquisition chain is proposed. Finally different use cases for this framework are presented.

Use of Low-Cost Acquisition Systems with an Embedded Linux Device for Volcanic Monitoring.

This paper describes the development of a low-cost multiparameter acquisition system for volcanic monitoring that is applicable to gravimetry and geodesy, as well as to the visual monitoring of volcanic activity. The acquisition system was developed using a System on a Chip (SoC) Broadcom BCM2835 Linux operating system (based on DebianTM) that allows for the construction of a complete monitoring system offering multiple possibilities for storage, data-processing, configuration, and the real-time monitoring of volcanic activity. This multiparametric acquisition system was developed with a software environment, as well as with different hardware modules designed for each parameter to be monitored. The device presented here has been used and validated under different scenarios for monitoring ocean tides, ground deformation, and gravity, as well as for monitoring with images the island of Tenerife and ground deformation on the island of El Hierro.

Revealing the cerebral regions and networks mediating vulnerability to depression: oxidative metabolism mapping of rat brain.

The large variety of available animal models has revealed much on the neurobiology of depression, but each model appears as specific to a significant extent, and distinction between stress response, pathogenesis of depression and underlying vulnerability is difficult to make. Evidence from epidemiological studies suggests that depression occurs in biologically predisposed subjects under impact of adverse life events. We applied the diathesis-stress concept to reveal brain regions and functional networks that mediate vulnerability to depression and response to chronic stress by collapsing data on cerebral long term neuronal activity as measured by cytochrome c oxidase histochemistry in distinct animal models. Rats were rendered vulnerable to depression either by partial serotonergic lesion or by maternal deprivation, or selected for a vulnerable phenotype (low positive affect, low novelty-related activity or high hedonic response). Environmental adversity was brought about by applying chronic variable stress or chronic social defeat. Several brain regions, most significantly median raphe, habenula, retrosplenial cortex and reticular thalamus, were universally implicated in long-term metabolic stress response, vulnerability to depression, or both. Vulnerability was associated with higher oxidative metabolism levels as compared to resilience to chronic stress. Chronic stress, in contrast, had three distinct patterns of effect on oxidative metabolism in vulnerable vs. resilient animals. In general, associations between regional activities in several brain circuits were strongest in vulnerable animals, and chronic stress disrupted this interrelatedness. These findings highlight networks that underlie resilience to stress, and the distinct response to stress that occurs in vulnerable subjects.

A new colorimetrically-calibrated automated video-imaging protocol for day-night fish counting at the OBSEA coastal cabled observatory.

Field measurements of the swimming activity rhythms of fishes are scant due to the difficulty of counting individuals at a high frequency over a long period of time. Cabled observatory video monitoring allows such a sampling at a high frequency over unlimited periods of time. Unfortunately, automation for the extraction of biological information (i.e., animals' visual counts per unit of time) is still a major bottleneck. In this study, we describe a new automated video-imaging protocol for the 24-h continuous counting of fishes in colorimetrically calibrated time-lapse photographic outputs, taken by a shallow water (20 m depth) cabled video-platform, the OBSEA. The spectral reflectance value for each patch was measured between 400 to 700 nm and then converted into standard RGB, used as a reference for all subsequent calibrations. All the images were acquired within a standardized Region Of Interest (ROI), represented by a 2 × 2 m methacrylate panel, endowed with a 9-colour calibration chart, and calibrated using the recently implemented "3D Thin-Plate Spline" warping approach in order to numerically define color by its coordinates in n-dimensional space. That operation was repeated on a subset of images, 500 images as a training set, manually selected since acquired under optimum visibility conditions. All images plus those for the training set were ordered together through Principal Component Analysis allowing the selection of 614 images (67.6%) out of 908 as a total corresponding to 18 days (at 30 min frequency). The Roberts operator (used in image processing and computer vision for edge detection) was used to highlights regions of high spatial colour gradient corresponding to fishes' bodies. Time series in manual and visual counts were compared together for efficiency evaluation. Periodogram and waveform analysis outputs provided very similar results, although quantified parameters in relation to the strength of respective rhythms were different. Results indicate that automation efficiency is limited by optimum visibility conditions. Data sets from manual counting present the larger day-night fluctuations in comparison to those derived from automation. This comparison indicates that the automation protocol subestimate fish numbers but it is anyway suitable for the study of community activity rhythms.

Regulation of serotonin (5-HT) function by a VGLUT1 dependent glutamate pathway.

Unraveling the mechanisms of 5-HT neuron control might provide new insights into depression pathophysiology. In addition to the inhibitory 5-HT1A autoreceptors, cortico-raphe glutamatergic descending pathways are suggested to modulate 5-HT activity in the DRN. Here we studied how decreased VGLUT1 levels in the brain stem affect glutamate regulation of 5-HT function. VGLUT1+/- mice (C57BL/6) and wild type (WT) littermates were used. VGLUT1 expression in the DRN, 5-HT turnover and immuno histochemical analysis of neuronal activity in different areas was studied. Moreover, the functionality of the inhibitory 5-HT1A autoreceptor was assessed using electrophysiological, biochemical and pharmacological approaches. VGLUT1 immunoreactivity was markedly lower in the DRN of the VGLUT1+/- mice and specifically, in the surroundings of GABA and 5-HT cell bodies. These mice showed decreased induced neuronal activity in 5-HT cells bodies and in different forebrain areas, as well as decreased hippocampal cell proliferation and 5-HT turnover. Further, 5-HT1A autoreceptor desensitization was evidenced by electrophysiological studies, GTP-γ-S coupling to 5-HT1A autoreceptor and a lower hypothermic response to 5-HT1A activation. This study shows first time that VGLUT1 dependent glutamate innervation of the DRN could modulate 5-HT function.

Accelerated aging of the GABAergic septohippocampal pathway and decreased hippocampal rhythms in a mouse model of Alzheimer's disease.

Patients with Alzheimer's disease (AD) display altered functioning of cortical networks, including altered patterns of synchronous activity and a serious deficit in cholinergic septohippocampal (SH) innervation. However, the mechanisms underlying these alterations and the implication of the GABAergic SH component in AD are largely unknown. In addition, the GABAergic septohippocampal pathway (SHP) is believed to regulate synchronous hippocampal activity by controlling the activity of interneurons. Here we show, using well-characterized pathway tracing experiments, that innervation of the GABAergic SHP decreases during normal aging. Furthermore, in an AD mouse model (hAPP(Sw,Ind); J20 mice), the GABAergic SHP shows a dramatic and early onset of this decrease in 8-mo-old mice. This decline is not caused by neuronal loss, but by the reduced number and complexity of GABAergic SH axon terminals. Finally, we demonstrate that hippocampal θ and γ rhythm power spectra are markedly diminished in 8-mo-old behaving mice expressing mutated hAPP. In addition to the well-known loss of cholinergic input to the hippocampus in AD, these data suggest that the altered patterns of synchronous activity seen in patients with AD could be caused by the loss of GABAergic SH axons, which modulate hippocampal network activities.

Ocean bottom seismometer: design and test of a measurement system for marine seismology.

The Ocean Bottom Seismometer (OBS) is a key instrument for the geophysical study of sea sub-bottom layers. At present, more reliable autonomous instruments capable of recording underwater for long periods of time and therefore handling large data storage are needed. This paper presents a new Ocean Bottom Seismometer designed to be used in long duration seismic surveys. Power consumption and noise level of the acquisition system are the key points to optimize the autonomy and the data quality. To achieve our goals, a new low power data logger with high resolution and Signal-to-Noise Ratio (SNR) based on Compact Flash memory card is designed to enable continuous data acquisition. The equipment represents the achievement of joint work from different scientific and technological disciplines as electronics, mechanics, acoustics, communications, information technology, marine geophysics, etc. This easy to handle and sophisticated equipment allows the recording of useful controlled source and passive seismic data, as well as other time varying data, with multiple applications in marine environment research. We have been working on a series of prototypes for ten years to improve many of the aspects that make the equipment easy to handle and useful to work in deep-water areas. Ocean Bottom Seismometers (OBS) have received growing attention from the geoscience community during the last forty years. OBS sensors recording motion of the ocean floor hold key information in order to study offshore seismicity and to explore the Earth's crust. In a seismic survey, a series of OBSs are placed on the seabed of the area under study, where they record either natural seismic activity or acoustic signals generated by compressed air-guns on the ocean surface. The resulting data sets are subsequently used to model both the earthquake locations and the crustal structure.

A new laboratory radio frequency identification (RFID) system for behavioural tracking of marine organisms.

Radio frequency identification (RFID) devices are currently used to quantify several traits of animal behaviour with potential applications for the study of marine organisms. To date, behavioural studies with marine organisms are rare because of the technical difficulty of propagating radio waves within the saltwater medium. We present a novel RFID tracking system to study the burrowing behaviour of a valuable fishery resource, the Norway lobster (Nephrops norvegicus L.). The system consists of a network of six controllers, each handling a group of seven antennas. That network was placed below a microcosm tank that recreated important features typical of Nephrops' grounds, such as the presence of multiple burrows. The animals carried a passive transponder attached to their telson, operating at 13.56 MHz. The tracking system was implemented to concurrently report the behaviour of up to three individuals, in terms of their travelled distances in a specified unit of time and their preferential positioning within the antenna network. To do so, the controllers worked in parallel to send the antenna data to a computer via a USB connection. The tracking accuracy of the system was evaluated by concurrently recording the animals' behaviour with automated video imaging. During the two experiments, each lasting approximately one week, two different groups of three animals each showed a variable burrow occupancy and a nocturnal displacement under a standard photoperiod regime (12 h light:12 h dark), measured using the RFID method. Similar results were obtained with the video imaging. Our implemented RFID system was therefore capable of efficiently tracking the tested organisms and has a good potential for use on a wide variety of other marine organisms of commercial, aquaculture, and ecological interest.

The new Seafloor Observatory (OBSEA) for remote and long-term coastal ecosystem monitoring.

A suitable sampling technology to identify species and to estimate population dynamics based on individual counts at different temporal levels in relation to habitat variations is increasingly important for fishery management and biodiversity studies. In the past two decades, as interest in exploring the oceans for valuable resources and in protecting these resources from overexploitation have grown, the number of cabled (permanent) submarine multiparametric platforms with video stations has increased. Prior to the development of seafloor observatories, the majority of autonomous stations were battery powered and stored data locally. The recently installed low-cost, multiparametric, expandable, cabled coastal Seafloor Observatory (OBSEA), located 4 km off of Vilanova i la Gertrú, Barcelona, at a depth of 20 m, is directly connected to a ground station by a telecommunication cable; thus, it is not affected by the limitations associated with previous observation technologies. OBSEA is part of the European Multidisciplinary Seafloor Observatory (EMSO) infrastructure, and its activities are included among the Network of Excellence of the European Seas Observatory NETwork (ESONET). OBSEA enables remote, long-term, and continuous surveys of the local ecosystem by acquiring synchronous multiparametric habitat data and bio-data with the following sensors: Conductivity-Temperature-Depth (CTD) sensors for salinity, temperature, and pressure; Acoustic Doppler Current Profilers (ADCP) for current speed and direction, including a turbidity meter and a fluorometer (for the determination of chlorophyll concentration); a hydrophone; a seismometer; and finally, a video camera for automated image analysis in relation to species classification and tracking. Images can be monitored in real time, and all data can be stored for future studies. In this article, the various components of OBSEA are described, including its hardware (the sensors and the network of marine and land nodes), software (data acquisition, transmission, processing, and storage), and multiparametric measurement (habitat and bio-data time series) capabilities. A one-month multiparametric survey of habitat parameters was conducted during 2009 and 2010 to demonstrate these functions. An automated video image analysis protocol was also developed for fish counting in the water column, a method that can be used with cabled coastal observatories working with still images. Finally, bio-data time series were coupled with data from other oceanographic sensors to demonstrate the utility of OBSEA in studies of ecosystem dynamics.

New serotonin 5-HT(1A) receptor agonists with neuroprotective effect against ischemic cell damage.

We report the synthesis of new compounds 4-35 based on structural modifications of different moieties of previously described lead UCM-2550. The new nonpiperazine derivatives, representing second-generation agonists, were assessed for binding affinity, selectivity, and functional activity at the 5-HT(1A) receptor (5-HT(1A)R). Computational ß(2)-based homology models of the ligand-receptor complexes were used to explain the observed structure-affinity relationships. Selected candidates were also evaluated for their potential in vitro and in vivo neuroprotective properties. Interestingly, compound 26 (2-{6-[(3,4-dihydro-2H-chromen-2-ylmethyl)amino]hexyl}tetrahydro-1H-pyrrolo[1,2-c]imidazole-1,3(2H)-dione) has been characterized as a high-affinity and potent 5-HT(1A)R agonist (K(i) = 5.9 nM, EC(50) = 21.8 nM) and exhibits neuroprotective effect in neurotoxicity assays in primary cell cultures from rat hippocampus and in the MCAO model of focal cerebral ischemia in rats.

Altered expression of neuronal tryptophan hydroxylase-2 mRNA in the dorsal and median raphe nuclei of three genetically modified mouse models relevant to depression and anxiety.

Depression and anxiety are among the leading causes of societal burden. Abnormalities in 5-hydroxytryptamine (5-HT; serotonin) neurotransmission are known to be associated with depressive and anxiety symptoms. The rostral projections of brainstem dorsal (DRN) and median (MRN) raphe nuclei are the main sources of forebrain 5-HT. The expression, turnover and distribution of tryptophan hydroxylase 2 (TPH2), the rate-limiting enzyme in 5-HT biosynthesis in the DRN and MRN are complex, in keeping with the existence of different subpopulations of 5-HT neurons in this area. In the present study, we measured the expression of TPH2 mRNA in the DRN and MRN using in situ hybridization in three genetically modified mouse models, all relevant to depression and anxiety, and matched wild-type controls. Our results show quantitative modifications in TPH2 mRNA expression in the three main subregions of the DRN as well as the MRN in relation to changes in serotonergic, glutamatergic and endocannabinoid neurotransmission systems. Thus, there were significant decreases in TPH2 transcript levels in 5-HT transporter (5-HTT)-/- mutant mice, whereas increases were observed in the vesicular glutamate transporter 1 hemi knock out (VGLUT1+/-) and cannabinoid receptor 1 mutant (CB1R-/-) mice. Based on these findings, we suggest that TPH2 mRNA expression is under the influence of multiple messenger systems in relation to presynaptic and/or postsynaptic feedback control of serotonin synthesis that, 5-HTT, VGLUT1 and CB1R seem to be involved in these feedback mechanisms. Finally, our data are in line with previous reports suggesting that TPH2 activity within different raphe subregions is differentially regulated under specific conditions.

Chronic mild stress in mice promotes cognitive impairment and CDK5-dependent tau hyperphosphorylation.

This study was undertaken to know whether cognition deficits produced by chronic mild stress (CMS) were associated with pathological markers of Alzheimer's disease (AD). The results show that the impairment in the Morris water maze test induced by CMS correlated with an increase in CDK5-dependent phospho-tau levels and with an increase in APP processing. Mice exposed to CMS may then constitute a non-transgenic model for sporadic forms of AD.

Enhanced expression of the voltage-dependent anion channel 1 (VDAC1) in Alzheimer's disease transgenic mice: an insight into the pathogenic effects of amyloid-ß.

The mitochondrial voltage-dependent anion channel 1 (VDAC1) is involved in the release of apoptotic proteins with possible relevance in Alzheimer's disease (AD) neuropathology. Through proteomic analysis followed by Western blotting and immunohistochemical techniques, we have found that VDAC1 is overexpressed in the hippocampus from amyloidogenic AD transgenic mice models. VDAC1 was also overexpressed in postmortem brain tissue from AD patients at an advanced stage of the disease. Interestingly, amyloid-ß (Aß) soluble oligomers were able to induce upregulation of VDAC1 in a human neuroblastoma cell line, further supporting a correlation between Aß levels and VDAC1 expression. In hippocampal extracts from transgenic mice, a significant increase was observed in the levels of VDAC1 phosphorylated at an epitope that is susceptible to phosphorylation by glycogen synthase kinase-3ß, whose activity was also increased. The levels of hexokinase I (HXKI), which interacts with VDAC1 and affects its function, were decreased in mitochondrial samples from AD models. Since phospho-VDAC and reduced HXKI levels favors a VDAC1 conformational state more prone to the release proapoptotic factors, regulation of the function of this channel may be a promising therapeutic approach to combat AD.