To investigate the impact of hyperbaric oxygen therapy (HBOT) on the cognitive function of mice with Alzheimer's disease (AD), while also identifying the cellular pathways associated with autophagy involved in the treatment. Twenty-four APP/PSl double transgenic mice were randomly assigned to either Group A or Group B, while another 24 C57 mice were randomly allocated to Group C or Group D. HBOT was administered to mice in Group B and Group D, and the Morris water maze test was used to assess changes in mice behavior. Histological examination using hematoxylin and eosin staining was conducted to observe pathological alterations in the hippocampus of the mice brain tissue. Polymerase chain reaction (PCR) was employed to analyze autophagy-related gene pathways in the hippocampus of the mice. Following HBOT, mice in Group B exhibited a significant reduction in escape latency and a notable increase in residence time within the target quadrant compared with Group A (P<0.05), as well as Group C and Group D (P<0.01). The hippocampal neurons in Group A and Group B mice exhibited disorganized arrangements, characterized by pyknosis and margination. Conversely, neurons in Group C displayed orderly arrangements, retaining intact structures with round nuclei demonstrating clear nuclear staining and normal morphology. The cellular morphology of mice in Group D remained unaffected. PCR analysis revealed no notable disparity in autophagy-related gene expression between Group A and Group C. However, the expression levels of five genes including Tgfb1, Mapk14, Bid, Atg7, and Akt1, were significantly elevated in Group B compared to Group A. HBOT has the potential to improve the cognitive function in mice modeled with AD. This improvement of cognitive function appears to be mediated by the up-regulation of autophagy-related genes, specifically Tgfb1, Mapk14, Bid, Atg7, and Akt1. These results indicate that HBOT may offer a therapeutic strategy for treating AD by enhancing autophagy mechanisms. Key words Alzheimer's disease, Autophagy, Hyperbaric oxygen, Morris water maze, PCR.

• MeSH
• Alzheimerova nemoc * terapie   metabolismus   genetika   psychologie   MeSH
• autofagie * fyziologie   MeSH
• hipokampus metabolismus   patologie   MeSH
• hyperbarická oxygenace * MeSH
• kognice * fyziologie   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední C57BL * MeSH
• myši transgenní * MeSH
• myši MeSH
• signální transdukce * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

High-intensity interval training (HIIT) is considered an effective therapy strategy for improving chronic pain associated with osteoarthritis (OA). Perineuronal nets (PNNs) are specialized extracellular matrix structures in the cerebral cortex that play a crucial role in regulating chronic pain. However, little is unknown whether HIIT could alleviate OA pain sensitization by reducing PNN levels. This study aimed to determine whether HIIT could reduce sensitivity of the affected joint(s) to pain in a chronic pain model in rats with OA. A rat model of interest was induced by intra-articular injection of monosodium iodoacetate (MIA) into the right knee. Thereafter, the mechanical withdrawal thresholds (MWTs) and PNN levels in the contralateral medial prefrontal cortex (mPFC) were measured in rats in the presence or absence of HIIT alone or in combination with injection of chondroitinase-ABC (ChABC) into the contralateral mPFC (inducing the degradation of PNNs), respectively. Results indicated that rats with OA exhibited significant reductions in MWTs, but a significant increase in the PNN levels; that HIIT reversed changes in MWTs and PNN levels in rats with OA, and that pretreatment of ChABC abolished effects of HIIT on MWTs, with PNN levels not changed. We concluded that pain sensitization in rats with OA may correlate with an increase in PNN levels in the mPFC, and that HIIT may increases OA pain-sensitive threshold by reduction of the PNN levels in the mPFC. Keywords: Osteoarthritis, Chronic pain, Pain sensitization, High-intensity interval training, Perineuronal nets.

• MeSH
• chronická bolest terapie   patofyziologie   MeSH
• extracelulární matrix metabolismus   MeSH
• kondiční příprava zvířat fyziologie   metody   MeSH
• krysa rodu rattus MeSH
• osteoartróza * terapie   MeSH
• potkani Sprague-Dawley * MeSH
• práh bolesti * MeSH
• prefrontální mozková kůra * metabolismus   MeSH
• vysoce intenzivní intervalový trénink * MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: Sex influences neurodegeneration, but it has been poorly investigated in dementia with Lewy bodies (DLB). We investigated sex differences in brain atrophy in DLB using magnetic resonance imaging (MRI). METHODS: We included 436 patients from the European-DLB consortium and the Mayo Clinic. Sex differences and sex-by-age interactions were assessed through visual atrophy rating scales (n = 327; 73 ± 8 years, 62% males) and automated estimations of regional gray matter volume and cortical thickness (n = 165; 69 ± 9 years, 72% males). RESULTS: We found a higher likelihood of frontal atrophy and smaller volumes in six cortical regions in males and thinner olfactory cortices in females. There were significant sex-by-age interactions in volume (six regions) and cortical thickness (seven regions) across the entire cortex. DISCUSSION: We demonstrate that males have more widespread cortical atrophy at younger ages, but differences tend to disappear with increasing age, with males and females converging around the age of 75. HIGHLIGHTS: Male DLB patients had higher odds for frontal atrophy on radiological visual rating scales. Male DLB patients displayed a widespread pattern of cortical gray matter alterations on automated methods. Sex differences in gray matter measures in DLB tended to disappear with increasing age.

• MeSH
• Alzheimerova nemoc * patologie   MeSH
• atrofie patologie   MeSH
• demence s Lewyho tělísky * diagnostické zobrazování   patologie   MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozková kůra patologie   MeSH
• pohlavní dimorfismus MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Patients with alcohol use disorder (AUD) who seek treatment show highly variable outcomes. A precision medicine approach with biomarkers responsive to new treatments is warranted to overcome this limitation. Promising biomarkers relate to prefrontal control mechanisms that are severely disturbed in AUD. This results in reduced inhibitory control of compulsive behavior and, eventually, relapse. We reasoned here that prefrontal dysfunction, which underlies vulnerability to relapse, is evidenced by altered neuroelectric signatures and should be restored by pharmacological interventions that specifically target prefrontal dysfunction. To test this, we applied our recently developed biocompatible neuroprosthesis to measure prefrontal neural function in a well-established rat model of alcohol addiction and relapse. We monitored neural oscillations and event-related potentials in awake alcohol-dependent rats during abstinence and following treatment with psilocybin or LY379268, agonists of the serotonin 2A receptor (5-HT2AR), and the metabotropic glutamate receptor 2 (mGluR2), that are known to reduce prefrontal dysfunction and relapse. Electrophysiological impairments in alcohol-dependent rats are reduced amplitudes of P1N1 and N1P2 components and attenuated event-related oscillatory activity. Psilocybin and LY379268 were able to restore these impairments. Furthermore, alcohol-dependent animals displayed a dominance in higher beta frequencies indicative of a state of hyperarousal that is prone to relapse, which particularly psilocybin was able to counteract. In summary, we provide prefrontal markers indicative of relapse and treatment response, especially for psychedelic drugs.

• MeSH
• alkoholismus * farmakoterapie   patofyziologie   MeSH
• aminokyseliny MeSH
• bicyklické sloučeniny heterocyklické * farmakologie   MeSH
• biologické markery MeSH
• evokované potenciály účinky léků   MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech * MeSH
• prefrontální mozková kůra * účinky léků   patofyziologie   metabolismus   MeSH
• psilocybin * farmakologie   MeSH
• receptory metabotropního glutamátu MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Single-photon optogenetics enables precise, cell-type-specific modulation of neuronal circuits, making it a crucial tool in neuroscience. Its miniaturization in the form of fully implantable wide-field stimulator arrays enables long-term interrogation of cortical circuits and bears promise for brain-machine interfaces for sensory and motor function restoration. However, achieving selective activation of functional cortical representations poses a challenge, as studies show that targeted optogenetic stimulation results in activity spread beyond one functional domain. While recurrent network mechanisms contribute to activity spread, here we demonstrate with detailed simulations of isolated pyramidal neurons from cats of unknown sex that already neuron morphology causes a complex spread of optogenetic activity at the scale of one cortical column. Since the shape of a neuron impacts its optogenetic response, we find that a single stimulator at the cortical surface recruits a complex spatial distribution of neurons that can be inhomogeneous and vary with stimulation intensity and neuronal morphology across layers. We explore strategies to enhance stimulation precision, finding that optimizing stimulator optics may offer more significant improvements than the preferentially somatic expression of the opsin through genetic targeting. Our results indicate that, with the right optical setup, single-photon optogenetics can precisely activate isolated neurons at the scale of functional cortical domains spanning several hundred micrometers.

• MeSH
• kočky MeSH
• modely neurologické MeSH
• mozková kůra fyziologie   cytologie   MeSH
• neurony fyziologie   MeSH
• optogenetika * metody   MeSH
• pyramidové buňky fyziologie   MeSH
• světelná stimulace metody   MeSH
• zvířata MeSH
• Check Tag
• kočky MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Posttraumatic stress disorder (PTSD) is associated with lower cortical thickness (CT) in prefrontal, cingulate, and insular cortices in diverse trauma-affected samples. However, some studies have failed to detect differences between PTSD patients and healthy controls or reported that PTSD is associated with greater CT. Using data-driven dimensionality reduction, we sought to conduct a well-powered study to identify vulnerable networks without regard to neuroanatomic boundaries. Moreover, this approach enabled us to avoid the excessive burden of multiple comparison correction that plagues vertex-wise methods. We derived structural covariance networks (SCNs) by applying non-negative matrix factorization (NMF) to CT data from 961 PTSD patients and 1124 trauma-exposed controls without PTSD. We used regression analyses to investigate associations between CT within SCNs and PTSD diagnosis (with and without accounting for the potential confounding effect of trauma type) and symptom severity in the full sample. We performed additional regression analyses in subsets of the data to examine associations between SCNs and comorbid depression, childhood trauma severity, and alcohol abuse. NMF identified 20 unbiased SCNs, which aligned closely with functionally defined brain networks. PTSD diagnosis was most strongly associated with diminished CT in SCNs that encompassed the bilateral superior frontal cortex, motor cortex, insular cortex, orbitofrontal cortex, medial occipital cortex, anterior cingulate cortex, and posterior cingulate cortex. CT in these networks was significantly negatively correlated with PTSD symptom severity. Collectively, these findings suggest that PTSD diagnosis is associated with widespread reductions in CT, particularly within prefrontal regulatory regions and broader emotion and sensory processing cortical regions.

• MeSH
• emoce MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozek MeSH
• posttraumatická stresová porucha * psychologie   MeSH
• prefrontální mozková kůra MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

The interaction between the main psychotropic ingredient of Cannabis, Δ9- tetrahydrocannabinol (THC), with the endogenous cannabinoid system (ECS) is a critical and underrated issue that deserves utmost attention. The ECS, indeed, contributes to the formation and regulation of excitatory and inhibitory (E/I) neuronal networks that in the hippocampus underly spatial memory. This study explored sex-specific consequences of prenatal exposure to THC in hippocampus-dependent memory and the underlying cellular and molecular contributors of synaptic plasticity and E/I homeostasis. Sprague Dawley dams were exposed to THC (2 mg/kg) or vehicle, from gestational day 5-20. The adolescent progeny of both sexes was tested for: spatial memory retrieval and flexibility in the Barnes Maze; mRNA expression of relevant players of hippocampal synaptic plasticity; density of cholecystokinin-positive basket cells (CCK+BCs) - a major subtype of hippocampal inhibitory interneurons; mRNA expression of the excitatory and inhibitory synaptic proteins neuroligins (Nlgns), as a proxy of synaptic efficiency. Our results show a sex-specific disruption in spatial memory retrieval and flexibility, a male-specific decrease in CCK+BCs density and increase in the expression of markers of neuroplasticity, and consistent changes in the expression of Nlgn-1 and 3 isoforms. Despite a delay in memory retrieval, flexibility of memory was spared in prenatally-THC-exposed female offspring as well as most of the markers of neuroplasticity; a sex-specific increase in CCK+BCs density, and a consistent expression of Nlgn-3 was observed. The current results highlight a major vulnerability to prenatal exposure to THC on memory processing in the male progeny, and sex-specific alterations in the E/I balance and synaptic plasticity.

• MeSH
• bludiště - učení účinky léků   MeSH
• cholecystokinin metabolismus   MeSH
• hipokampus * účinky léků   metabolismus   MeSH
• krysa rodu rattus MeSH
• neuroplasticita * účinky léků   MeSH
• pohlavní dimorfismus * MeSH
• potkani Sprague-Dawley * MeSH
• prostorová paměť * účinky léků   MeSH
• těhotenství MeSH
• tetrahydrokanabinol * farmakologie   toxicita   MeSH
• zpožděný efekt prenatální expozice * chemicky indukované   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Major depressive disorder (MDD) is a mental illness with a high worldwide prevalence and suboptimal pharmacological treatment, which necessitates the development of novel, more efficacious MDD medication. Nuclear magnetic resonance (NMR) can non-invasively provide insight into the neurochemical state of the brain using proton magnetic resonance spectroscopy (1H MRS), and an assessment of regional cerebral blood flow (rCBF) by perfusion imaging. These methods may provide valuable in vivo markers of the pathological processes underlying MDD. METHODS: This study examined the effects of the chronic antidepressant medication, citalopram, in a well-validated MDD model induced by bilateral olfactory bulbectomy (OB) in rats. 1H MRS was utilized to assess key metabolite ratios in the dorsal hippocampus and sensorimotor cortex bilaterally, and arterial spin labelling was employed to estimate rCBF in several additional brain regions. RESULTS: The 1H MRS data results suggest lower hippocampal Cho/tCr and lower cortical NAA/tCr levels as a characteristic of the OB phenotype. Spectroscopy revealed lower hippocampal Tau/tCr in citalopram-treated rats, indicating a potentially deleterious effect of the drug. However, the significant OB model-citalopram treatment interaction was observed using 1H MRS in hippocampal mI/tCr, Glx/tCr and Gln/tCr, indicating differential treatment effects in the OB and control groups. The perfusion data revealed higher rCBF in the whole brain, hippocampus and thalamus in the OB rats, while citalopram appeared to normalise it without affecting the control group. CONCLUSION: Collectively, 1H MRS and rCBF approaches demonstrated their capacity to capture an OB-induced phenotype and chronic antidepressant treatment effect in multiple brain regions.

• MeSH
• bulbus olfactorius metabolismus   chirurgie   účinky léků   MeSH
• citalopram * farmakologie   MeSH
• deprese farmakoterapie   metabolismus   MeSH
• depresivní porucha unipolární farmakoterapie   metabolismus   MeSH
• hipokampus metabolismus   účinky léků   MeSH
• krysa rodu rattus MeSH
• magnetická rezonanční spektroskopie metody   MeSH
• modely nemocí na zvířatech * MeSH
• mozek * metabolismus   účinky léků   MeSH
• mozkový krevní oběh * účinky léků   MeSH
• potkani Sprague-Dawley MeSH
• protonová magnetická rezonanční spektroskopie MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: The hippocampal representation of space, formed by the collective activity of populations of place cells, is considered as a substrate of spatial memory. Alzheimer's disease (AD), a widespread severe neurodegenerative condition of multifactorial origin, typically exhibits spatial memory deficits among its early clinical signs before more severe cognitive impacts develop. OBJECTIVE: To investigate mechanisms of spatial memory impairment in a double transgenic rat model of AD. METHODS: In this study, we utilized 9-12-month-old double-transgenic TgF344-AD rats and age-matched controls to analyze the spatial coding properties of CA1 place cells. We characterized the spatial memory representation, assessed cells' spatial information content and direction-specific activity, and compared their population coding in familiar and novel conditions. RESULTS: Our findings revealed that TgF344-AD animals exhibited lower precision in coding, as evidenced by reduced spatial information and larger receptive zones. This impairment was evident in maps representing novel environments. While controls instantly encoded directional context during their initial exposure to a novel environment, transgenics struggled to incorporate this information into the newly developed hippocampal spatial representation. This resulted in impairment in orthogonalization of stored activity patterns, an important feature directly related to episodic memory encoding capacity. CONCLUSIONS: Overall, the results shed light on the nature of impairment at both the single-cell and population levels in the transgenic AD model. In addition to the observed spatial coding inaccuracy, the findings reveal a significantly impaired ability to adaptively modify and refine newly stored hippocampal memory patterns.

• MeSH
• Alzheimerova nemoc * patofyziologie   MeSH
• amyloidový prekurzorový protein beta genetika   MeSH
• hipokampální oblast CA1 patofyziologie   MeSH
• hipokampus patofyziologie   MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• modely nemocí na zvířatech * MeSH
• poruchy paměti etiologie   patofyziologie   MeSH
• potkani inbrední F344 MeSH
• potkani transgenní * MeSH
• prostorová paměť fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

A subpopulation of astrocytes on the brain's surface, known as subpial astrocytes, constitutes the "glia limitans superficialis" (GLS), which is an interface between the brain parenchyma and the cerebrospinal fluid (CSF) in the subpial space. Changes in connexin-43 (Cx43) and aquaporin-4 (AQP4) proteins in subpial astrocytes were examined in the medial prefrontal cortex at postoperative day 1, 3, 7, 14, and 21 after sham operation and sciatic nerve compression (SNC). In addition, we tested the altered uptake of TRITC-conjugated 3 kDa dextran by reactive subpial astrocytes. Cellular immunofluorescence (IF) detection and image analysis were used to examine changes in Cx43 and AQP4 protein levels, as well as TRITC-conjugated 3 kDa dextran, in subpial astrocytes. The intensity of Cx43-IF was significantly increased, but AQP4-IF decreased in subpial astrocytes of sham- and SNC-operated rats during all survival periods compared to naïve controls. Similarly, the uptake of 3 kDa dextran in the GLS was reduced following both sham and SNC operations. The results suggest that both sciatic nerve injury and peripheral tissue injury alone can induce changes in subpial astrocytes related to the spread of their reactivity across the cortical surface mediated by increased amounts of gap junctions. At the same time, water transport and solute uptake were impaired in subpial astrocytes.

• MeSH
• akvaporin 4 * metabolismus   MeSH
• astrocyty * metabolismus   MeSH
• dextrany * metabolismus   MeSH
• konexin 43 * metabolismus   MeSH
• krysa rodu rattus MeSH
• nervus ischiadicus * zranění   metabolismus   MeSH
• potkani Sprague-Dawley MeSH
• prefrontální mozková kůra * metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH