Acid-sensing ion channels (ASICs) are proton-gated ion channels that mediate nociception in the peripheral nervous system and contribute to fear and learning in the central nervous system. Sevanol was reported previously as a naturally-occurring ASIC inhibitor from thyme with favorable analgesic and anti-inflammatory activity. Using electrophysiological methods, we found that in the high micromolar range, the compound effectively inhibited homomeric ASIC1a and, in sub- and low-micromolar ranges, positively modulated the currents of α1β2γ2 GABA_A receptors. Next, we tested the compound in anxiety-related behavior models using a targeted delivery into the hippocampus with parallel electroencephalographic measurements. In the open field, 6 µM sevanol reduced both locomotor and θ-rhythmic activity similar to GABA, suggesting a primary action on the GABAergic system. At 300 μM, sevanol markedly suppressed passive avoidance behavior, implying alterations in conditioned fear memory. The observed effects could be linked to distinct mechanisms involving GABA_AR and ASIC1a. These results elaborate the preclinical profile of sevanol as a candidate for drug development and support the role of ASIC channels in fear-related functions of the hippocampus.

One month of calorically restricted diet (CR) induced morphological plasticity of astrocytes in the stratum (str.) radiatum of hippocampal CA1 in three-months old mice: the volume fraction of distal perisynaptic astrocytic processes increased whereas the number of gap-junction coupled astrocytes decreased. The uncoupling was not associated with a decrease in the expression of connexin 43. Uncoupling and morphological remodeling affected spontaneous Ca ²⁺ activity in the astrocytic network: Ca ²⁺ events became longer, whereas their spread was reduced. The change in the pattern of astrocytic Ca ²⁺ activity may increase the spatial resolution of the information encoding in the astroglial network. Consistent with expanded synaptic enwrapping by the astroglial processes, the spillover of synaptically released K ⁺ and glutamate was diminished after CR. However, no significant changes in the expression of astrocytic glutamate transporter (GLT-1/EAAT2) were observed, although the level of glutamine synthetase was decreased. Glutamate uptake is known to regulate the synaptic plasticity. Indeed, the magnitude of long-term potentiation (LTP) in the glutamatergic CA3-CA1 synapses was significantly enhanced after CR. Our findings highlight an astroglial basis for improved learning and memory reported in various species subjected to CR.

One of the attractive targets for the relief of stress conditions is TRPV1, which is expressed mostly in primary afferent neurons (nociceptors) and in the central nervous system, mainly in the cortex and hippocampus. We evaluated the action of a potent low-molecular-weight antagonist of TRPV1 (AMG517) and peptide modulator of this channel (APHC3) on long-term potentiation (LTP) and Paired-Pulse Ratio (PPR) in the CA3-CA1 region of the hippocampus of mice. In vivo, we used intranasal administration to provide effective peptide delivery into the brain and analyzed the effects of APHC3 in acute stress tests in comparison with intramuscular administration of APHC3, AMG517, and the reference anxiolytic drug Fabomotizole (Fab). In electrophysiology studies, APHC3 significantly enhanced LTP and PPR, while AMG517 enhanced only PPR. Intranasal administration of APHC3 to mice provided a moderate anxiolytic effect in the single dose (0.01 mg/kg). Intramuscular administration of APHC3 and AMG517 significantly reduced acute stress in mice equal to the reference drug Fab. Thus, TRPV1 modulation in either the peripheral or central nervous system is sufficient to produce an anxiolytic-like effect, likely through distinct underlying mechanisms.

Non-human primates (NHPs) provide an essential translational platform for investigating neural mechanisms underlying brain aging and neurodegenerative diseases. Their neuroanatomical organization, cortical complexity, and cognitive capacities share close parallels with those of humans, enabling a degree of experimental precision that rodent models cannot achieve. Electroencephalography (EEG) offers a non-invasive method for monitoring neuronal population activity with high temporal resolution, capturing oscillatory patterns and connectivity changes that emerge over the course of aging and in pathological states. In humans, such measures have revealed alterations in dominant frequency bands, network synchrony, and event-related potentials that serve as candidate biomarkers for cognitive decline. Extending EEG to NHP models permits the direct examination of mechanistic hypotheses and assessment of therapeutic interventions in a brain closely resembling that of humans. We emphasize study-level examples and quantitative anchors, including frequency-band ranges and the direction of EEG changes across aging and neurodegenerative disease models. Recent work has expanded EEG applications in NHPs to longitudinal studies, invasive/non-invasive signal comparisons, and integration with other modalities, including magnetoencephalography (MEG), functional magnetic resonance imaging (fMRI), functional near-infrared spectroscopy (fNIRS), and invasive electrophysiology. Furthermore, pairing EEG with neuromodulation techniques such as transcranial magnetic stimulation (TMS), transcranial direct and alternating current stimulation (tDCS, tACS), temporal interference (TI) stimulation, and transcranial focused ultrasound (tFUS) offers a framework for causally probing and modifying network function. This review synthesizes EEG methodologies in NHPs, examines their applications to models of normative aging, Alzheimer’s disease, and Parkinson’s disease, and discusses multimodal integration, neuromodulation strategies, ethical considerations, and translational relevance for human neuroscience. Sections are organized around five linked goals: establishing EEG measurement validity in primates, summarizing aging and disease-associated EEG signatures, integrating EEG with imaging and invasive recordings, using stimulation to test causality, and translating biomarkers and interventions to human studies.

Aging is a key challenge for modern society. In particular, brain aging is accompanied by chronic inflammation, depletion of energy potential, and an increased level of oxidative stress, with changes in blood composition playing a special role in this process. Recent studies also show that aging progresses non-linearly throughout life. Primates are genetically and anthropometrically the closest laboratory animals to humans, thus representing the most accurate model for research. This study establishes baseline values for biochemical parameters (including the state of the body’s antioxidant system), cellular-hematological, and genomic indicators in aging primates of various species, sexes, and ages from the Kurchatov Complex of Medical Primatology. In aging males, the concentration of lipid peroxidation products was lower than in females of the same age and species. Analysis of antioxidant defense parameters indicates a more stable redox balance in old cynomolgus macaques of both sexes, which may be associated with their lower aggressiveness and high adaptability. The biochemical profile analysis in aging rhesus macaques revealed that females exhibit elevated levels of all measured parameters. In aging cynomolgus macaques, there are fewer sex-related differences in blood composition characteristics compared to rhesus macaques. It can be noted that under the housing conditions of the primates at the nursery of the Kurchatov Complex of Medical Primatology, several types of aging based on blood parameters can be observed within the same age category across different species and sexes.