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PubMed1976

The metabolism of glucose of nerve cells cultivated under different conditions.

1. The consumption of glucose and formation of lactate was studied in medium of long-term cultivated nerve tissue. Fragments of chicken brain embryo dissociated and reaggregated brain cells were cultivated in Rose chambers, Falcon plastic dishes and Erlenmayer flasks. 2. Dissociated cells were cultivated in Petri dishes in media containing 100 mg/100 ml glucose. Consumption of glucose and formation of lactate increases until the 9th day. Glucose is completely exhausted in the medium up to the 2nd week of cultivation. 3. The time curve of both glucose consumption and lactate production is similar in cultures cultivated in Rose chambers, Petri dishes and Falcon plastic dishes. Cultures in Rose chambers utilize glucose at later stages anaerobically, whereas in Petri dishes and Falcon plastic dishes approximately 25% is utilized by aerobic glycolysis. 4. Cells dissociated by trypsinization and sieving are metabolically more active than cells separated mechanically (sieving only). During later stages of cultivation of enzymatically dissociated cells in 100 mg/100 ml glucose, lactate is utilized like a substrate, because of concentration of glucose in the medium is not being sufficient. 5. The concentration of glucose is essential for utilization by the aerobic pathway. In dissociated cells, cultivated in media enriched by 400 mg/100 ml of glucose in Falcon plastic dishes 75% of aerobic glycolysis is found during first 10 days and 50% in later stages. In the same system, cultivated in 100 mg/100 ml of glucose, glucose is exhausted up to the 12th day and lactate is utilized as a substrate. 6. In the close system of cultivation, i.e. in Rose chambers, 50% of glucose is utilized by the aerobic pathway if the medium contains 400 mg/100 ml of glucose. Early cultivation period of dissociated cells in Falcon plastic dishes is slowed, because cells adhere slowly to the plastic ground. 7. Structural development of cultures and differentiation of cells was studied during the cultivation period. Cells cultivated in elevated glucose concentration exhibit signs of better differentiation.

Aerobiosis↗
PubMed2026

Effects of strength and balance training on the structure of the aging brain.

BACKGROUND: While it is established that motor training induces structural changes in the brains of young adults, structural adaptations in aging brains are less studied. METHODS: This randomized controlled study investigated the impact of long-term strength and balance training on the structural plasticity in 60 elderly adults (64 - 82 years old, 70.6 ± 4.7) using multi-modal neuroimaging. We compared the effects of three months of strength training to balance training of the same duration and to a passive control group. Voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) were used to assess grey matter (GM) and white matter (WM) plasticity. White matter tract integrity (WMTI) modelling was employed to explore the microstructural underpinnings of white matter alterations. RESULTS: We found that strength training was associated with changes in diffusion metrics consistent with white matter microstructural remodeling, specifically increased extra-axonal axial diffusivity in the bilateral inferior fronto-occipital and longitudinal fasciculi. Additionally, both balance and strength training mitigated reductions in axonal water fraction in the splenium of the corpus callosum and the right posterior corona radiata observed in the control group. CONCLUSION: These results underscore the potential relevance of strength and balance training to induce beneficial neural plasticity by counteracting aging-related demyelination in the corpus callosum and highlight the specific role of strength training in facilitating white matter reorganization in key transmission fiber pathways.

Humans↗
PubMed2026

Adaptations to breath-hold diving: from traditional divers to elite athletes.

Breath-hold diving exposes humans to repeated episodes of profound hypoxia and hypercapnia, eliciting physiological adaptations that enable prolonged underwater performance. This article summarises current knowledge on chronic adaptations in elite breath-hold athletes and traditional diving populations, including the Bajau sea nomads of Southeast Asia and the Korean Haenyeo divers. Evidence indicates that repeated apnoea induces adaptations across multiple physiological systems. Haematological changes include increased spleen size and enhanced splenic contraction, augmenting circulating haemoglobin and oxygen stores during apnoea. In elite divers, structured training can increase resting spleen volume, whereas the Bajau exhibit genetically associated splenic enlargement linked to variants near the PDE10A gene. Cardiopulmonary adaptations include modified pulmonary vascular responses to hypoxia, improved oxygen conservation, and metabolic shifts favoring efficient mitochondrial energy production. Molecular adaptations involve enhanced antioxidant defenses and activation of hypoxia-responsive pathways that may mitigate oxidative stress associated with repeated hypoxia-reoxygenation cycles. Emerging evidence also suggests neural plasticity and possible structural brain adaptations, although the long-term neurological consequences of chronic intermittent hypoxia exposure remain uncertain. Studies of traditional diving populations indicate that both phenotypic plasticity and genetic selection contribute to diving capacity, highlighting interactions between training and evolution. Despite these benefits, breath-hold diving also carries risks, including hypoxic blackout, decompression sickness, and potential neurological injury. Understanding the mechanisms underlying human tolerance to extreme hypoxia may have implications beyond diving physiology, including applications in cardiovascular medicine, hypoxic diseases, and rehabilitation. Further longitudinal, genomic, and mechanistic studies are needed to clarify the limits, benefits, and clinical relevance of these adaptations.

Humans↗
PubMed2026

Ketogenic diet dampens excitatory neurotransmission by shrinking synaptic vesicle pools.

Ketogenic diet (KD) is used for the treatment of drug-resistant childhood epilepsy and has been proposed to improve outcomes in neurodegenerative diseases. However, the mechanisms by which KD alters brain circuitry remain unclear. Here, we investigated the impact of KD on hippocampal function through integrative analysis of gene expression and neurotransmission. We found that KD induces extensive transcriptional reprogramming, including altered expression of numerous synaptic genes. Proteomic and genomic profiling revealed significant changes in histone modifications, particularly at promoters of KD-regulated genes. Electrophysiological recordings showed that KD reduces excitatory synaptic gain and short-term plasticity at CA3-CA1 synapses, dampening the summation of excitatory inputs and enhancing the summation of inhibitory inputs. These functional changes were driven, in part, by a reduction in the readily releasable vesicle pool at excitatory synapses under KD. Together, our findings demonstrate that KD drives transcriptional remodeling of hippocampal circuits, leading to synaptic adaptations that may underlie its anti-epileptic and neuroprotective effects.

Animals↗
PubMed2026

Genome-wide mapping of stress-responsive lncRNA, uc.104, reveals the chromatin-mediated regulation of stress and plasticity-related genes in the hippocampus of chronic restraint rats.

Chronic stress significantly impacts hippocampal function through transcriptional and epigenetic mechanisms. While the roles of lncRNAs in stress-related transcriptional and epigenetic regulation have recently been recognized, their genome-wide functions controlling the transcriptional network remain largely unclear. Evidence indicates that the lncRNA uc.104 is involved in stress responses; however, its genome-wide chromatin interactions and gene regulatory effects are yet to be explored. To examine this, we combined chromatin isolation by RNA purification sequencing (ChIRP-seq) and RNA sequencing (RNA-seq) in the hippocampus from handled control and chronic restraint stress (CRS) rats. ChIRP-seq identified 6,664 uc.104 binding peaks under CRS, including 6,517 enriched and 149 reduced. Many peaks were mapped to intronic and promoter-proximal regions of protein-coding genes. Integration of ChIRP-seq with RNA-seq data revealed 1,839 differentially expressed genes associated with uc.104 binding sites, with 106 high-confidence overlaps. Several genes (Gabra3, Htr7, Irs1, Gpr37, Clu, Hspa1b, Ppp3r2, Nfasc, Pcdhac2, and Cysltr2) identified as regulatory targets of uc.104, have been directly implicated in stress responses, synaptic plasticity, and neuroinflammation. Gene ontology and Synapse GO (SynGO) analyses revealed significant enrichment for processes involving dendritic spine formation, synapse organization, and pre- and postsynaptic signaling. Protein-protein interaction analysis identified hub genes, including EGFR, CDC42, IGF1R, CTNNB1, CALM1, CALM3, POLR2A, MDM2, TBP, and CSNK1E, several of which have been linked to stress-responsive pathways. Together, our findings reveal that uc.104 binding to chromatin near stress- and synapse-related genes may act as a regulator of stress-responsive transcriptional networks in the hippocampus. By linking uc.104 occupancy to stress and synaptic responsive genes, this study highlights uc.104 as a potential mediator of stress-induced hippocampal malfunctions.

Animals↗
PubMed2026

Faster N1 latency in response to homeostatic-like plasticity of PREPs is impaired during pain: A randomized-placebo capsaicin-pain study.

INTRODUCTION: Homeostatic-like plasticity (HP-like) stabilizes cortical excitability through long-term potentiation and depression-like mechanisms. The efficacy of homeostatic regulation in the corticomotor system is impaired during pain, which may have functional relevance for chronic pain. This study investigated whether a cortical HP-like response could be assessed by nociceptive stimulation, and if such response was impaired by experimental tonic pain. METHODS: Twenty-eight healthy participants completed placebo and capsaicin sessions, with 11 sham controls for time and design. HP-like plasticity was induced with two blocks of anodal tDCS over the primary motor cortex. The N1 (TP7) and N2P2 (Cz) components of electrically induced pain-related evoked potentials (PREPs) were assessed from the volar forearm before and after patch application, and again immediately and 20 min after HP-like induction. An HP-like response was defined by PREP decrease after induction, and further normalization to baseline. RESULTS: Anodal tDCS did not induce an HP-like regulation of PREP amplitudes. Interestingly, an HP-like response was observed as a fastening of N1 latency after HP-like induction, which returned to baseline values after 20 min. The latter effect was impaired during capsaicin-induced pain, where N1 was slower. The N2P2 component showed habituation over time in all sessions. CONCLUSION: This is the first study that investigates the HP-like regulation of nociceptive-evoked responses. An HP-like response was observed as a shortening of N1 latency, suggesting that early nociceptive processing may be susceptible to homeostatic regulation. In contrast, the later component, N2P2, showed habituation over time, which prevented evaluation of HP-like effects.

Humans↗
PubMed2026

Effectiveness of passive vs. assistive robotic gait training on functional recovery and neuroplasticity post-stroke: A randomized controlled trial.

OBJECTIVE: This study seeks to compare the impacts of various robotic gait training (RAGT) modes on lower limb motor function recovery in stroke patients while exploring the corresponding neural mechanisms. DESIGN: A single-blind, randomized controlled trial. SETTING: Inpatient Rehabilitation Facility. PARTICIPANTS: Forty-eight patients aged 18-80 who had experienced their first unilateral subacute stroke accompanied by walking impairments were included. INTERVENTIONS: Participants were randomly assigned to: (1) assistive mode training, (2) passive mode training, or (3) control group receiving only traditional rehabilitation. Clinical and neurological outcomes were assessed at pre-intervention (T0), and post-2-week intervention (T1). MAIN OUTCOME MEASURES: Outcomes were evaluated using the Fugl-Meyer Assessment for Lower Extremity, Berg Balance Scale, Modified Barthel Index, the Functional Ambulatory Category, and functional near-infrared spectroscopy. RESULTS: Among the 48 patients recruited, significant time effects were observed across all groups in FMA-LE scores (p&#x202f;<&#x202f;0.001). Notable improvements were detected in the conventional group (MD = 2.69, p&#xff1c;0.01) and the passive group (MD = 3.67, p&#x202f;<&#x202f;0.001), with the assistive mode also demonstrating a significant effect (MD = 1.79, p&#x202f;<&#x202f;0.05). BBS scores improved across all groups; however, no significant differences were noted between the groups (p&#x202f;=&#x202f;0.11). Similarly, MBI scores showed a significant time effect (p&#x202f;<&#x202f;0.001), without notable group differences (p&#x202f;=&#x202f;0.29). CONCLUSION: All training modalities effectively enhanced motor function, balance, and daily living skills in stroke patients. Distinct cortical activation and connectivity patterns were observed between training modalities, which may reflect different neuroplastic mechanisms. These preliminary neural differences may help inform personalized rehabilitation strategies, although no clinical superiority of one mode over another can be concluded from the present data.

Humans↗
PubMed2026

Transcranial Magnetic Stimulation for Patients with Exposure Therapy Resistant Obsessive-Compulsive Disorder (TETRO): Study Protocol for a Multicenter Randomized Controlled Trial.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a disabling mental disorder, characterized by obsessions, compulsions, and substantial morbidity. Approximately 50% of adults with OCD fail to achieve satisfactory outcomes from first-line treatments, such as exposure therapy with response prevention (ERP), with or without medication. This leads to chronic social, educational, and occupational impairment. While invasive procedures such as deep brain stimulation are available for severe, treatment-refractory cases, a need remains for less invasive alternatives. Repetitive transcranial magnetic stimulation (rTMS), a noninvasive intervention, shows promise in reducing OCD symptoms. Unlike in depression, rTMS is not yet reimbursed for OCD in the Dutch healthcare system. OBJECTIVE: This study examines the efficacy and cost-effectiveness of low-frequency (1Hz) rTMS targeting the presupplementary motor area (pre-SMA) compared to sham rTMS as an adjuvant treatment to ERP in adults with OCD with inadequate response to first-line treatment. METHODS: A total of 250 adults with OCD will be enrolled in this multicenter randomized controlled trial. Participants will be randomly assigned to ERP combined with either active or sham 1Hz rTMS over the pre-SMA. Treatment is administered 4 times weekly for at least 5 weeks (20 rTMS-ERP sessions), with optional extension of 1 to 2 weeks, up to 28 rTMS-ERP sessions. Clinical assessments occur at baseline, weekly during treatment, posttreatment, and at 3, 6, and 12 months follow-up. Participants undergo pre- and posttreatment (functional) (MRI) scans, including a symptom provocation task. Blood sampling takes place pre- and posttreatment and at 3-month follow-up. The primary outcome is OCD severity at posttreatment, as measured by the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Secondary outcomes include functional improvement, quality of life, and societal costs. Pretreatment symptom profiles, genotype, and brain network topology will be analyzed as predictors of response and relapse risk. Pre-to-post treatment change in blood-based and magnetic resonance (MR)-based neuroplasticity markers will help explore differential mechanisms between ERP alone and combined rTMS-ERP. We expect that the verum rTMS protocol will be cost-effective compared to sham-rTMS. RESULTS: Recruitment started in April 2022, and as of February 2026, 201 participants have been enrolled. Posttreatment assessments are projected to be completed in December 2026, with final one-year follow-up evaluations anticipated by the end of 2027. CONCLUSIONS: To our knowledge, this study is the first adequately powered randomized controlled trial examining efficacy, cost-effectiveness, and mechanism of action of rTMS for OCD as adjuvant therapy to ERP. In case of efficacy and/or cost-effectiveness, it will pave the way for rTMS as insured health care for adults with OCD in the Netherlands, and possibly other European countries. Furthermore, this trial will provide insight into the mechanisms of treatment response to intensive ERP, with and without adjunctive rTMS, as well as potential side effects, individual variability, and long-term outcomes in adults with OCD.

Humans↗
PubMed1979

Neuronal mechanisms of conitioned placing reactions in cats.

Neuronal correlates of conditioned placing reaction of cat’s forepaw were studied. The conditioned reaction evoking by tactile stimulation of the paw’s ventral side had the same motor pattern, consisting mainly in successive flexion and extension of elbow joint, as the placing reaction evoked by paw’s dorsal side stimulation in naive animals. The activity of single neurons from the m. biceps representation area in pericruciate motor cortex and VL thalamic nucleus was recorded. As a result of learning the excitatory response of cortical neurons to paw’s ventral side stimulation in 20-50 ms post-stimulus interval was 2-2.5 times more than the response to the same stimulation in naive cats. This short-latency increase of response was not accompanied by modifications of sensory inflow to the motor cortex or movement related afferentation changes arriving from VL nucleus. There were no marked differences in excitability of cortical neurons of naive and trained animals as well. The results suggest a functional plasticity of the neuronal net in the motor cortex, consisting of a change in the efficiency of connections between neurons receiving sensory determined afferent excitation and the functional groups of neurons controlling the contraction of different muscles.

Animals↗
PubMed1975

Neuronal activities in human epileptic foci and surrounding areas.

1. Extracellular microelectrode recording was carried out in human epileptogenic cortex and in the area surrounding the focus in three cases and in the hippocampus of two cases. 2. It was impossible to identify primary "epileptic" or "pacemaker" neurons. Emphasis is placed on the interactions among the neuronal aggregates at the focus for generating the epileptic discharges in the interictal stage. The possibility of plasticity in each neuronal element in the epileptogenicity is considered. Surround inhibition was not observed. The slow wave burst was accompanied by a long repetitive rhythymic burst of unitary discharge. It was shown that the slow wave burst was a modified feature of epileptic activity. 3. Various types of activity of hippocampal neurons are described, which are, however, considered as normal discharges of those neurons.

Action Potentials↗
PubMed2005

Tissue specificity and regulation of the N-terminal diversity of reticulon 3.

Over the last few years, the widely distributed family of reticulons (RTNs) is receiving renewed interest because of the implication of RTN4/Nogo in neurite regeneration. Four genes were identified in mammals and are referred to as RTN1, 2, 3 and the neurite outgrowth inhibitor RTN4/Nogo. In the present paper, we describe the existence of five new isoforms of RTN3 that differ in their N-termini, and analysed their tissue distribution and expression in neurons. We redefined the structure of human and murine rtn3 genes, and identified two supplementary exons that may generate up to seven putative isoforms arising by alternative splicing or differential promoter usage. We confirmed the presence of five of these isoforms at the mRNA and protein levels, and showed their preferential expression in the central nervous system. We analysed rtn3 expression in the cerebellum further, and observed increased levels of several of the RTN3 isoforms during cerebellum development and during in vitro maturation of cerebellar granule cells. This pattern of expression paralleled that shown by RTN4/Nogo isoforms. Specifically, RTN3A1 expression was down-regulated upon cell death of cerebellar granule neurons triggered by potassium deprivation. Altogether, our results demonstrate that the rtn3 gene generates multiple isoforms varying in their N-termini, and that their expression is tightly regulated in neurons. These findings suggest that RTN3 isoforms may contribute, by as yet unknown mechanisms, to neuronal survival and plasticity.

Alternative Splicing↗
PubMed1979

Pulvinar and lateral geniculate neuronal activity in the cat during operantly conditioned appetitive behavior.

Cats were trained to press a lever for 0.5--1.0 ml of milk reward both in the presence and absence of ambient light. 'Floating' microelectrodes were implanted in the pulvinar and lateral geniculate nuclei to allow chronic recording from single or multiple neurons over a period of 1--16 days. Thirty-one of 36 pulvinar neurons (86%) showed a consistent periodicity in the firing rate that was clearly related to certain phases of operant behavior. In the presence of ambient light, the firing rate was maximal shortly prior to or immediately after a rewarded bar press, particularly during the animal's initial contact with reward (the first lap). This burst of activity was followed by an abrupt and strong inhibition of firing which was, in most instances, associated with high voltage slow wave (6--9 c/sec) postreinforcement synchronization (PRS) of the electroencephalogram over the visual and association cortices as well as in the pulvinar. Postreinforcement inhibition of neuronal activity was also observed in the lateral geniculate. Neuronal firing in both nuclei dropped significantly below the respective mean rate observed for each nucleus during relaxed wakefulness. In the dark, however, the reward-induced inhibition was abolished in both nuclei. Moreover, some pulvinar neurons in the dark showed a conspicuous and significant increase in firing during the consummatory response (dark reversal pattern). These findings suggest that a transient but powerful inhibitory process triggered by positive reinforcement depends on visual input. Firing patterns of some pulvinar neurons were noted to be entrained not only by the rhythm of PRS oscillations (inhibitory phasing and postinhibitory discharges) but also by the much slower 3--4 c/sec rhythm of lapping and licking. Furthermore, the patterns of entrainment by initial lapping appear to be different from those observed during the later phase of the consummatory response, thus indicating that the pulvinar may receive information regarding the content of the delivery cup. No entrainment of neuronal activity was observed in the lateral geniculate. These findings reveal remarkable plasticity in the pulvinar neurons that is consistent with their role in polysensory integration.

Action Potentials↗
PubMed1979

Ontogeny of behavioral development, arousal and stereotypes in two strains of mice.

A number of reflexes and amphetamine-induced locomotor and stereotyped behavior were assesses in 8, 16, 32, 90 and 360 day old C57BL/6J and SEC/1ReJ inbred mice. The data indicate that C57 mice are more precocious for a number of neuronal and behavioral mechanisms while SEC mice are less mature at birth. In addition, there are appreciable fluctuations of these behavioral patterns throughout life. A rise in arousal levels was evident in both strains between 8 and 16 days and between 32 and 90 days of age. Three-hundred-sixty days old mice presented a general decrease in the levels of arousal. These findings are discussed in terms of neuronal and behavioral plasticity and in relation to the ontogeny of the different catecholaminergic systems which modulate excitory and inhibitory different behavioral patterns at different ages.

Aging↗