-
Alzheimer's & Dementia : the Journal of... Jun 2024Animal research has shown that tau pathology in the locus coeruleus (LC) is associated with reduced norepinephrine signaling, lower projection density to the medial...
INTRODUCTION
Animal research has shown that tau pathology in the locus coeruleus (LC) is associated with reduced norepinephrine signaling, lower projection density to the medial temporal lobe (MTL), atrophy, and cognitive impairment. We investigated the contribution of LC-MTL functional connectivity (FC) on cortical atrophy across Braak stage regions and its impact on cognition.
METHODS
We analyzed functional magnetic resonance imaging and amyloid beta (Aβ) positron emission tomography data from 128 cognitively normal participants, associating novelty-related FC with longitudinal atrophy and cognition with and without Aβ moderation.
RESULTS
Cross-sectionally, lower FC was associated with atrophy in Braak stage II regions. Longitudinally, atrophy in Braak stage 2 to 4 regions related to lower baseline FC at elevated levels of Aβ, but not to other regions. Atrophy in Braak stage 2 regions mediated the relation between FC and subsequent cognitive decline.
DISCUSSION
FC is implicated in Aβ-related cortical atrophy, suggesting that LC-MTL connectivity could confer neuroprotective effects in preclinical AD.
HIGHLIGHTS
Novelty-related functional magnetic resonance imaging (fMRI) LC-medial temporal lobe (MTL) connectivity links to longitudinal Aβ-dependent atrophy. This relationship extended to higher Braak stage regions with increasing Aβ burden. Longitudinal MTL atrophy mediated the LC-MTL connectivity-cognition relationship. Our findings mirror the animal data on MTL atrophy following NE signal dysfunction.
Topics: Humans; Locus Coeruleus; Male; Female; Atrophy; Cognitive Dysfunction; Magnetic Resonance Imaging; Aged; Positron-Emission Tomography; Alzheimer Disease; Cross-Sectional Studies; Temporal Lobe; Amyloid beta-Peptides; Longitudinal Studies; Neural Pathways
PubMed: 38676563
DOI: 10.1002/alz.13839 -
International Journal of Molecular... Apr 2024According to previous studies, the median raphe region (MRR) is known to contribute significantly to social behavior. Besides serotonin, there have also been reports of...
According to previous studies, the median raphe region (MRR) is known to contribute significantly to social behavior. Besides serotonin, there have also been reports of a small population of dopaminergic neurons in this region. Dopamine is linked to reward and locomotion, but very little is known about its role in the MRR. To address that, we first confirmed the presence of dopaminergic cells in the MRR of mice (immunohistochemistry, RT-PCR), and then also in humans (RT-PCR) using healthy donor samples to prove translational relevance. Next, we used chemogenetic technology in mice containing the Cre enzyme under the promoter of the dopamine transporter. With the help of an adeno-associated virus, designer receptors exclusively activated by designer drugs (DREADDs) were expressed in the dopaminergic cells of the MRR to manipulate their activity. Four weeks later, we performed an extensive behavioral characterization 30 min after the injection of the artificial ligand (Clozapine-N-Oxide). Stimulation of the dopaminergic cells in the MRR decreased social interest without influencing aggression and with an increase in social discrimination. Additionally, inhibition of the same cells increased the friendly social behavior during social interaction test. No behavioral changes were detected in anxiety, memory or locomotion. All in all, dopaminergic cells were present in both the mouse and human samples from the MRR, and the manipulation of the dopaminergic neurons in the MRR elicited a specific social response.
Topics: Animals; Dopaminergic Neurons; Male; Mice; Social Behavior; Humans; Clozapine; Raphe Nuclei; Behavior, Animal; Dopamine; Mice, Inbred C57BL
PubMed: 38673899
DOI: 10.3390/ijms25084315 -
Journal of Clinical Medicine Apr 2024(1) : Dislocations of the trapeziometacarpal joint (TMC) are uncommon in children and adolescents. Only a few isolated cases are reported in the literature. Therapeutic... (Review)
Review
(1) : Dislocations of the trapeziometacarpal joint (TMC) are uncommon in children and adolescents. Only a few isolated cases are reported in the literature. Therapeutic guidance is minimal and inconclusive. (2) : The authors present four patients treated for this unusual lesion. We evaluated the evolution according to treatment, age, patient activity, and quickDASH. Despite the clear limitation of the small number of patients, it is relevant to try to better understand this lesion and its evolution. A systematic review of the literature was also conducted. (3) : This is the largest published series of TMC dislocations in children and adolescents. Patients included a 12-year-old girl treated conservatively with a poor quickDASH; a 9-year-old girl treated surgically with the Eaton-Littler technique for a new dislocation with a partially modified quickDASH; a 13-year-old boy with two necessary closed reductions for a new dislocation and a very good final quickDASH; and a 12-year-old boy treated with closed reduction and percutaneous fixation with excellent final results with quickDASH. (4) : In the absence of scientific evidence, conservative treatment and ligament reconstruction did not provide good functionality. In contrast, closed reduction with percutaneous fixation provided excellent results. Therefore, the authors would recommend closed reduction and percutaneous needle fixation as an elective method to treat TMC dislocations in pediatric and adolescent patients.
PubMed: 38673470
DOI: 10.3390/jcm13082197 -
BMC Infectious Diseases Apr 2024Streptococcus suis is one of the most common zoonotic pathogens, in humans and can cause meningitis, endocarditis, arthritis and sepsis. Human cases of Streptococcus...
Streptococcus suis is one of the most common zoonotic pathogens, in humans and can cause meningitis, endocarditis, arthritis and sepsis. Human cases of Streptococcus suis infection have been reported worldwide, and most of those cases occurred in Asia. Hearing loss is the most common sequela of Streptococcus suis meningitis. Streptococcus suis infection complicated with acute cerebral infarction has rarely been reported. Therefore, to provide a reference for this disease, we reported a case of acute multiple brain infarctions associated with Streptococcus suis infection. In our report, a 69yearold male patient had Streptococcus suis meningitis and sepsis, which were associated with multiple acute cerebral infarctions in the pons and bilateral frontotemporal parietal occipital lobes. After treatment, the patient exhibited cognitive impairment, dyspraxia and irritability. There are limited case reports of cerebral infarction associated with Streptococcus suis infection, and further research is needed to determine the best treatment method.
Topics: Humans; Streptococcus suis; Male; Streptococcal Infections; Aged; Brain Infarction; Meningitis, Bacterial; Sepsis; Anti-Bacterial Agents
PubMed: 38671388
DOI: 10.1186/s12879-024-09318-9 -
Science Advances Apr 2024The supraspinal descending pain modulatory system (DPMS) shapes pain perception via monoaminergic modulation of sensory information in the spinal cord. However, the role...
The supraspinal descending pain modulatory system (DPMS) shapes pain perception via monoaminergic modulation of sensory information in the spinal cord. However, the role and synaptic mechanisms of descending noradrenergic signaling remain unclear. Here, we establish that noradrenergic neurons of the locus coeruleus (LC) are essential for supraspinal opioid antinociception. While much previous work has emphasized the role of descending serotonergic pathways, we find that opioid antinociception is primarily driven by excitatory output from the ventrolateral periaqueductal gray (vlPAG) to the LC. Furthermore, we identify a previously unknown opioid-sensitive inhibitory input from the rostroventromedial medulla (RVM), the suppression of which disinhibits LC neurons to drive spinal noradrenergic antinociception. We describe pain-related activity throughout this circuit and report the presence of prominent bifurcating outputs from the vlPAG to the LC and the RVM. Our findings substantially revise current models of the DPMS and establish a supraspinal antinociceptive pathway that may contribute to multiple forms of descending pain modulation.
Topics: Locus Coeruleus; Periaqueductal Gray; Animals; Medulla Oblongata; Pain; Analgesics, Opioid; Male; Adrenergic Neurons; Mice; Neural Pathways
PubMed: 38669335
DOI: 10.1126/sciadv.adj9581 -
Nature Aging May 2024Autopsy studies indicated that the locus coeruleus (LC) accumulates hyperphosphorylated tau before allocortical regions in Alzheimer's disease. By combining in vivo...
Autopsy studies indicated that the locus coeruleus (LC) accumulates hyperphosphorylated tau before allocortical regions in Alzheimer's disease. By combining in vivo longitudinal magnetic resonance imaging measures of LC integrity, tau positron emission tomography imaging and cognition with autopsy data and transcriptomic information, we examined whether LC changes precede allocortical tau deposition and whether specific genetic features underlie LC's selective vulnerability to tau. We found that LC integrity changes preceded medial temporal lobe tau accumulation, and together these processes were associated with lower cognitive performance. Common gene expression profiles between LC-medial temporal lobe-limbic regions map to biological functions in protein transport regulation. These findings advance our understanding of the spatiotemporal patterns of initial tau spreading from the LC and LC's selective vulnerability to Alzheimer's disease pathology. LC integrity measures can be a promising indicator for identifying the time window when individuals are at risk of disease progression and underscore the importance of interventions mitigating initial tau spread.
Topics: Locus Coeruleus; Humans; tau Proteins; Alzheimer Disease; Cognition; Positron-Emission Tomography; Male; Female; Aged; Magnetic Resonance Imaging; Aged, 80 and over; Temporal Lobe
PubMed: 38664576
DOI: 10.1038/s43587-024-00626-y -
Journal of Neurology, Neurosurgery, and... Apr 2024Alzheimer's disease (AD)-related neuropathological changes can occur decades before clinical symptoms. We aimed to investigate whether neurodevelopment and/or...
BACKGROUND
Alzheimer's disease (AD)-related neuropathological changes can occur decades before clinical symptoms. We aimed to investigate whether neurodevelopment and/or neurodegeneration affects the risk of AD, through reducing structural brain reserve and/or increasing brain atrophy, respectively.
METHODS
We used bidirectional two-sample Mendelian randomisation to estimate the effects between genetic liability to AD and global and regional cortical thickness, estimated total intracranial volume, volume of subcortical structures and total white matter in 37 680 participants aged 8-81 years across 5 independent cohorts (Adolescent Brain Cognitive Development, Generation R, IMAGEN, Avon Longitudinal Study of Parents and Children and UK Biobank). We also examined the effects of global and regional cortical thickness and subcortical volumes from the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium on AD risk in up to 37 741 participants.
RESULTS
Our findings show that AD risk alleles have an age-dependent effect on a range of cortical and subcortical brain measures that starts in mid-life, in non-clinical populations. Evidence for such effects across childhood and young adulthood is weak. Some of the identified structures are not typically implicated in AD, such as those in the striatum (eg, thalamus), with consistent effects from childhood to late adulthood. There was little evidence to suggest brain morphology alters AD risk.
CONCLUSIONS
Genetic liability to AD is likely to affect risk of AD primarily through mechanisms affecting indicators of brain morphology in later life, rather than structural brain reserve. Future studies with repeated measures are required for a better understanding and certainty of the mechanisms at play.
PubMed: 38663994
DOI: 10.1136/jnnp-2023-332969 -
Frontiers in Immunology 2024Bickerstaff brainstem encephalitis (BBE) is a rare disease considered caused by acute demyelination of the brainstem, most often resulting from secondary autoimmune...
BACKGROUND
Bickerstaff brainstem encephalitis (BBE) is a rare disease considered caused by acute demyelination of the brainstem, most often resulting from secondary autoimmune responses. To our knowledge, this is the first probable case report of shingles-associated BBE with anti-sulfatide IgM positivity.
CASE PRESENTATION
We report the case of an 83-year-old woman with symptoms of progressive limb weakness, difficulty swallowing food, and disturbed consciousness that occurred 4 weeks following herpes zoster infection. Autoimmune anti-sulfatide antibodies were positive and fluid-attenuated inversion recovery (FLAIR) sequences revealed clear high signal intensity in pons and bilateral thalamus. Our patient's condition improved markedly with glucocorticoid treatment. After 2 months of treatment, our patient was fully recovered. We considered that for her case, BBE is the most appropriate diagnosis.
CONCLUSIONS
We emphasize the importance of a careful medical history and assessment of clinical symptoms, performing MRI, testing autoimmune antibodies for rapid diagnosis, and ruling out differential diagnoses. Further studies involving more patients with BBE with IgM anti-sulfatide autoantibodies will increase the understanding of the clinical characteristics and advance the diagnosis and treatment of this syndrome. Meanwhile, it is crucial for dermatologists to know about this severe neurological complication following shingles.
Topics: Humans; Female; Brain Stem; Aged, 80 and over; Immunoglobulin M; Autoantibodies; Encephalitis; Sulfoglycosphingolipids; Magnetic Resonance Imaging; Glucocorticoids
PubMed: 38660303
DOI: 10.3389/fimmu.2024.1358886 -
Brazilian Journal of Medical and... 2024We aimed to develop a prognostic model for primary pontine hemorrhage (PPH) patients and validate the predictive value of the model for a good prognosis at 90 days. A...
We aimed to develop a prognostic model for primary pontine hemorrhage (PPH) patients and validate the predictive value of the model for a good prognosis at 90 days. A total of 254 PPH patients were included for screening of the independent predictors of prognosis, and data were analyzed by univariate and multivariable logistic regression tests. The cases were then divided into training cohort (n=219) and validation cohort (n=35) based on the two centers. A nomogram was developed using independent predictors from the training cohort to predict the 90-day good outcome and was validated from the validation cohort. Glasgow Coma Scale score, normalized pixels (used to describe bleeding volume), and mechanical ventilation were significant predictors of a good outcome of PPH at 90 days in the training cohort (all P<0.05). The U test showed no statistical difference (P=0.892) between the training cohort and the validation cohort, suggesting the model fitted well. The new model showed good discrimination (area under the curve=0.833). The decision curve analysis of the nomogram of the training cohort indicated a great net benefit. The PPH nomogram comprising the Glasgow Coma Scale score, normalized pixels, and mechanical ventilation may facilitate predicting a 90-day good outcome.
Topics: Humans; Female; Male; Prognosis; Glasgow Coma Scale; Nomograms; Middle Aged; Adult; Respiration, Artificial; Pons; Predictive Value of Tests; Aged; Reproducibility of Results; Intracranial Hemorrhages; Retrospective Studies
PubMed: 38656075
DOI: 10.1590/1414-431X2024e13359 -
Biology of Sex Differences Apr 2024The lateral habenula (LHb) is an epithalamus nucleus that is evolutionarily conserved and involved in various physiological functions, such as encoding value signals,...
BACKGROUND
The lateral habenula (LHb) is an epithalamus nucleus that is evolutionarily conserved and involved in various physiological functions, such as encoding value signals, integrating emotional information, and regulating related behaviors. The cells in the LHb are predominantly glutamatergic and have heterogeneous functions in response to different stimuli. The circuitry connections of the LHb glutamatergic neurons play a crucial role in integrating a wide range of events. However, the circuitry connections of LHb glutamatergic neurons in both sexes have not been thoroughly investigated.
METHODS
In this study, we injected Cre-dependent retrograde trace virus and anterograde synaptophysin-labeling virus into the LHb of adult male and female Vglut2-ires-Cre mice, respectively. We then quantitatively analyzed the input and output of the LHb glutamatergic connections in both the ipsilateral and contralateral whole brain.
RESULTS
Our findings showed that the inputs to LHb neurons come from more than 30 brain subregions, including the cortex, striatum, pallidum, thalamus, hypothalamus, midbrain, pons, medulla, and cerebellum with no significant differences between males and females. The outputs of LHb neurons targeted eight large brain regions, primarily focusing on the midbrain and pons nuclei, with distinct features in presynaptic bouton across different brain subregions. While correlation and cluster analysis revealed differences in input and collateral projection features, the input-output connection pattern of LHb neurons in both sexes was highly similar.
CONCLUSIONS
This study provides a systematic and comprehensive analysis of the input and output connections of LHb neurons in male and female mice, shedding light on the anatomical architecture of these specific cell types in the mouse LHb. This structural understanding can help guide further investigations into the complex functions of the LHb.
Topics: Animals; Female; Male; Habenula; Neurons; Sex Characteristics; Glutamic Acid; Vesicular Glutamate Transport Protein 2; Neural Pathways; Mice
PubMed: 38654275
DOI: 10.1186/s13293-024-00611-5