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Stem Cell Research Mar 2016Radiation therapy is a standard treatment for brain tumor patients. However, it comes with side effects, such as neurological deficits. While likely multi-factorial, the... (Review)
Review
Radiation therapy is a standard treatment for brain tumor patients. However, it comes with side effects, such as neurological deficits. While likely multi-factorial, the effect may in part be associated with the impact of radiation on the neurogenic niches. In the adult mammalian brain, the neurogenic niches are localized in the subventricular zone (SVZ) of the lateral ventricles and the dentate gyrus of the hippocampus, where the neural stem cells (NSCs) reside. Several reports showed that radiation produces a drastic decrease in the proliferative capacity of these regions, which is related to functional decline. In particular, radiation to the SVZ led to a reduced long-term olfactory memory and a reduced capacity to respond to brain damage in animal models, as well as compromised tumor outcomes in patients. By contrast, other studies in humans suggested that increased radiation dose to the SVZ may be associated with longer progression-free survival in patients with high-grade glioma. In this review, we summarize the cellular and functional effects of irradiating the SVZ niche. In particular, we review the pros and cons of using radiation during brain tumor treatment, discussing the complex relationship between radiation dose to the SVZ and both tumor control and toxicity.
Topics: Animals; Brain; Carcinogenesis; Humans; Lateral Ventricles; Neural Stem Cells; Stem Cell Niche
PubMed: 26921873
DOI: 10.1016/j.scr.2016.02.031 -
Scientific Reports Aug 2021Removing function from a developed and functional sensory system is known to alter both cerebral morphology and functional connections. To date, a majority of studies...
Removing function from a developed and functional sensory system is known to alter both cerebral morphology and functional connections. To date, a majority of studies assessing sensory-dependent plasticity have focused on effects from either early onset or long-term sensory loss and little is known how the recent sensory loss affects the human brain. With the aim of determining how recent sensory loss affects cerebral morphology and functional connectivity, we assessed differences between individuals with acquired olfactory loss (duration 7-36 months) and matched healthy controls in their grey matter volume, using multivariate pattern analyses, and functional connectivity, using dynamic connectivity analyses, within and from the olfactory cortex. Our results demonstrate that acquired olfactory loss is associated with altered grey matter volume in, among others, posterior piriform cortex, a core olfactory processing area, as well as the inferior frontal gyrus and angular gyrus. In addition, compared to controls, individuals with acquired anosmia displayed significantly stronger dynamic functional connectivity from the posterior piriform cortex to, among others, the angular gyrus, a known multisensory integration area. When assessing differences in dynamic functional connectivity from the angular gyrus, individuals with acquired anosmia had stronger connectivity from the angular gyrus to areas primary responsible for basic visual processing. These results demonstrate that recently acquired sensory loss is associated with both changed cerebral morphology within core olfactory areas and increase dynamic functional connectivity from olfactory cortex to cerebral areas processing multisensory integration.
Topics: Aged; Anosmia; Brain; Brain Mapping; Case-Control Studies; Female; Gray Matter; Humans; Male; Middle Aged; Support Vector Machine
PubMed: 34385571
DOI: 10.1038/s41598-021-95968-7 -
Journal of Clinical Medicine May 2023The efficacy of electroconvulsive therapy (ECT) in the treatment of adolescents with treatment-refractory depression is still unsatisfactory, and the individual...
OBJECTS
The efficacy of electroconvulsive therapy (ECT) in the treatment of adolescents with treatment-refractory depression is still unsatisfactory, and the individual differences are large. It is not clear which factors are related to the treatment effect. Resting-state fMRI may be a good tool to predict the clinical efficacy of this treatment, and it is helpful to identify the most suitable population for this treatment.
METHODS
Forty treatment-refractory depression adolescents were treated by ECT and evaluated using HAMD and BSSI scores before and after treatment, and were then divided into a treatment response group and a non-treatment group according to the reduction rate of the HAMD scale. We extracted the ALFF, fALFF, ReHo, and functional connectivity of patients as predicted features after a two-sample -test and LASSO to establish and evaluate a prediction model of ECT in adolescents with treatment-refractory depression.
RESULTS
Twenty-seven patients achieved a clinical response; symptoms of depression and suicidal ideation were significantly improved after treatment with ECT, which was reflected in a significant decrease in the scores of HAMD and BSSI ( < 0.001). The efficacy was predicted by ALFF, fALFF, ReHo, and whole-brain-based functional connectivity. We found that models built on a subset of features of ALFF in the left insula, fALFF in the left superior parietal gyrus, right superior parietal gyrus, and right angular, and functional connectivity between the left superior frontal gyrus, dorsolateral-right paracentral lobule, right middle frontal gyrus, orbital part-left cuneus, right olfactory cortex-left hippocampus, left insula-left thalamus, and left anterior cingulate gyrus-right hippocampus to have the best predictive performance (AUC > 0.8).
CONCLUSIONS
The local brain function in the insula, superior parietal gyrus, and angular gyrus as well as characteristic changes in the functional connectivity of cortical-limbic circuits may serve as potential markers for efficacy judgment of ECT and help to provide optimized individual treatment strategies for adolescents with depression and suicidal ideation in the early stages of treatment.
PubMed: 37240663
DOI: 10.3390/jcm12103556 -
Brain : a Journal of Neurology Aug 2019Generalized convulsive status epilepticus is a life-threatening emergency, because recurrent convulsions can cause death or injury. A common form of generalized...
Generalized convulsive status epilepticus is a life-threatening emergency, because recurrent convulsions can cause death or injury. A common form of generalized convulsive status epilepticus is of focal onset. The neuronal circuits activated during seizure spread from the hippocampus, a frequent site of seizure origin, to the bilateral motor cortex, which mediates convulsive seizures, have not been delineated. Status epilepticus was initiated by electrical stimulation of the hippocampus. Neurons transiently activated during seizures were labelled with tdTomato and then imaged following brain slice clearing. Hippocampus was active throughout the episode of status epilepticus. Neuronal activation was observed in hippocampus parahippocampal structures: subiculum, entorhinal cortex and perirhinal cortex, septum, and olfactory system in the initial phase status epilepticus. The tdTomato-labelled neurons occupied larger volumes of the brain as seizures progressed and at the peak of status epilepticus, motor and somatosensory cortex, retrosplenial cortex, and insular cortex also contained tdTomato-labelled neurons. In addition, motor thalamic nuclei such as anterior and ventromedial, midline, reticular, and posterior thalamic nuclei were also activated. Furthermore, circuits proposed to be crucial for systems consolidation of memory: entorhinal cortex, retrosplenial cortex, cingulate gyrus, midline thalamic nuclei and prefrontal cortex were intensely active during periods of generalized tonic-clonic seizures. As the episode of status epilepticus waned, smaller volume of brain was activated. These studies suggested that seizure spread could have occurred via canonical thalamocortical pathway and many cortical structures involved in memory consolidation. These studies may help explain retrograde amnesia following seizures.
Topics: Amnesia, Retrograde; Animals; Brain; Brain Mapping; Cerebral Cortex; Electroshock; Genes, Reporter; Hippocampus; Memory Consolidation; Mice; Neural Pathways; Neurons; Olfactory Bulb; Seizures; Single-Blind Method; Status Epilepticus; Thalamic Nuclei
PubMed: 31237945
DOI: 10.1093/brain/awz170 -
BioRxiv : the Preprint Server For... Sep 2023Schizophrenia is marked by poor social functioning that can have a severe impact on quality of life and independence, but the underlying neural circuity is not well...
Schizophrenia is marked by poor social functioning that can have a severe impact on quality of life and independence, but the underlying neural circuity is not well understood. Here we used a translational model of subanesthetic ketamine in mice to delineate neural pathways in the brain linked to social deficits in schizophrenia. Mice treated with chronic ketamine (30 mg/kg/day for 10 days) exhibit profound social and sensorimotor deficits as previously reported. Using three- dimensional c-Fos immunolabeling and volume imaging (iDISCO), we show that ketamine treatment resulted in hypoactivation of the lateral septum (LS) in response to social stimuli. Chemogenetic activation of the LS rescued social deficits after ketamine treatment, while chemogenetic inhibition of previously active populations in the LS (i.e. social engram neurons) recapitulated social deficits in ketamine-naïve mice. We then examined the translatome of LS social engram neurons and found that ketamine treatment dysregulated genes implicated in neuronal excitability and apoptosis, which may contribute to LS hypoactivation. We also identified 38 differentially expressed genes (DEGs) in common with human schizophrenia, including those involved in mitochondrial function, apoptosis, and neuroinflammatory pathways. Chemogenetic activation of LS social engram neurons induced downstream activity in the ventral part of the basolateral amygdala, subparafascicular nucleus of the thalamus, intercalated amygdalar nucleus, olfactory areas, and dentate gyrus, and it also reduces connectivity of the LS with the piriform cortex and caudate-putamen. In sum, schizophrenia-like social deficits may emerge via changes in the intrinsic excitability of a discrete subpopulation of LS neurons that serve as a central hub to coordinate social behavior via downstream projections to reward, fear extinction, motor and sensory processing regions of the brain.
PubMed: 37609170
DOI: 10.1101/2023.08.08.552372 -
Journal of Neurochemistry Dec 2018In the adult mammalian brain, neural stem cells (NSCs) reside in two neurogenic regions, the walls of the lateral ventricles, and the subgranular zone of the... (Review)
Review
In the adult mammalian brain, neural stem cells (NSCs) reside in two neurogenic regions, the walls of the lateral ventricles, and the subgranular zone of the hippocampus, which generate new neurons for the olfactory bulb and dentate gyrus, respectively. These adult NSCs retain their self-renewal ability and capacity to differentiate into neurons and glia as demonstrated by in vitro studies. However, their contribution to tissue repair in disease and injury is limited, lending credence to the claim by prominent neuropathologist Ramón y Cajal that 'once development was ended, the founts of growth and regeneration of the axons and dendrites dried up irrevocably'. However, recent progress toward understanding the fundamental biology of adult NSCs and their role in pathological conditions has provided new insight into the potential therapeutic utility of endogenous NSCs. In this short review, we highlight two topics: the altered behavior of NSCs after brain damage and the dysfunction of NSCs and oligodendrocyte precursor cells, another type of undifferentiated cell in the adult brain, in mood affective disorders.
Topics: Brain; Brain Injuries; Humans; Mental Disorders; Mood Disorders; Neural Stem Cells; Neurogenesis; Oligodendroglia
PubMed: 30028510
DOI: 10.1111/jnc.14557 -
Brain and Behavior Apr 2023In patients with mild cognitive impairment, pathological changes begin in the amygdala (AMG) and hippocampus (HI), especially in the parahippocampal gyrus and entorhinal...
INTRODUCTION
In patients with mild cognitive impairment, pathological changes begin in the amygdala (AMG) and hippocampus (HI), especially in the parahippocampal gyrus and entorhinal cortex (ENT). These areas play an important role in olfactory detection and recognition. It is important to understand how subtle signs of olfactory disability relate to the functions of the above-mentioned regions, as well as the orbitofrontal cortex (OFC). In this study, we evaluated brain activation using functional magnetic resonance imaging (fMRI), performed during the presentation of olfactory stimuli (classified as "normal odors" not inducing memory retrieval), and investigated the relationships of the blood oxygen level-dependent (BOLD) signal with olfactory detection and recognition abilities in healthy elderly subjects.
METHODS
Twenty-four healthy elderly subjects underwent fMRI during olfaction, and raw mean BOLD signals were extracted from regions of interest, including bilateral regions (AMG, HI, parahippocampus, and ENT) and orbitofrontal subregions (frontal inferior OFC, frontal medial OFC, frontal middle OFC, and frontal superior OFC). Multiple regression and path analyses were conducted to understand the roles of these areas in olfactory detection and recognition.
RESULTS
Activation of the left AMG had the greatest impact on olfactory detection and recognition, while the ENT, parahippocampus, and HI acted as a support system for AMG activation. Less activation of the right frontal medial OFC was associated with good olfactory recognition. These findings improve our understanding of the roles of limbic and prefrontal regions in olfactory awareness and identification in elderly individuals.
CONCLUSION
Functional decline of the ENT and parahippocampus crucially impacts olfactory recognition. However, AMG function may compensate for deficits through connections with frontal regions.
Topics: Humans; Aged; Odorants; Amygdala; Brain; Smell; Recognition, Psychology; Magnetic Resonance Imaging
PubMed: 36897168
DOI: 10.1002/brb3.2956 -
Acta Radiologica (Stockholm, Sweden :... Sep 2022Coronaviruses may lead to invasion of the central nervous system.
BACKGROUND
Coronaviruses may lead to invasion of the central nervous system.
PURPOSE
To investigate the effects of COVID-19 infection on smell using cranial magnetic resonance imaging (MRI).
MATERIAL AND METHODS
Cranial MRI scans of 23 patients with COVID-19 (patient group [PG]) and 23 healthy controls (HCs) were evaluated. Peripheric (olfactory bulb [OB] volume and olfactory sulcus [OS] depth) and central (insular gyrus and corpus amygdala areas) smell regions were measured.
RESULTS
Smell loss was present in nine patients (39.1%) in the PG. The means of the disease duration and antiviral treatment were 3.00 ± 2.35 and 5.65 ± 1.72 days, respectively. OB volumes of the PG were significantly lower than those of the HCs bilaterally. However, no significant differences were observed between the OS depth, insular gyrus, and corpus amygdala areas of both groups. The left corpus amygdala areas were both increased with the increased disease ( = 0.035, r = 0.442) and treatment durations ( = 0.037, r = 0.438). In the PG, longer treatment duration, increase in C-reactive protein (CRP), lymphocyte count decrease, and positive thoracic computed tomography (CT) involvement were related to OS depth decrease. Right corpus amygdala areas increased in patients with COVID-19 with increased D-dimer values, and thoracic CT involvement was detected.
CONCLUSION
COVID-19 disease affects the peripheric smell region of OBs and does not affect the central smell regions of the insular gyrus and corpus amygdala areas. The importance of our study is to detect MRI findings in patients with COVID-19 leading to odor disorders. These findings may help in diagnosing the disease at an early stage.
Topics: COVID-19; Humans; Magnetic Resonance Imaging; Olfaction Disorders; Olfactory Bulb; Smell
PubMed: 34282630
DOI: 10.1177/02841851211034043 -
European Journal of Nuclear Medicine... Aug 2021In the context of the worldwide outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), some patients report functional complaints after apparent...
PURPOSE
In the context of the worldwide outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), some patients report functional complaints after apparent recovery from COVID-19. This clinical presentation has been referred as "long COVID." We here present a retrospective analysis of F-FDG brain PET of long COVID patients from the same center with a biologically confirmed diagnosis of SARS-CoV-2 infection and persistent functional complaints at least 3 weeks after the initial infection.
METHODS
PET scans of 35 patients with long COVID were compared using whole-brain voxel-based analysis to a local database of 44 healthy subjects controlled for age and sex to characterize cerebral hypometabolism. The individual relevance of this metabolic profile was evaluated to classify patients and healthy subjects. Finally, the PET abnormalities were exploratory compared with the patients' characteristics and functional complaints.
RESULTS
In comparison to healthy subjects, patients with long COVID exhibited bilateral hypometabolism in the bilateral rectal/orbital gyrus, including the olfactory gyrus; the right temporal lobe, including the amygdala and the hippocampus, extending to the right thalamus; the bilateral pons/medulla brainstem; the bilateral cerebellum (p-voxel < 0.001 uncorrected, p-cluster < 0.05 FWE-corrected). These metabolic clusters were highly discriminant to distinguish patients and healthy subjects (100% correct classification). These clusters of hypometabolism were significantly associated with more numerous functional complaints (brainstem and cerebellar clusters), and all associated with the occurrence of certain symptoms (hyposmia/anosmia, memory/cognitive impairment, pain and insomnia) (p < 0.05). In a more preliminary analysis, the metabolism of the frontal cluster which included the olfactory gyrus was worse in the 7 patients treated by ACE drugs for high blood pressure (p = 0.032), and better in the 3 patients that had used nasal decongestant spray at the infectious stage (p < 0.001).
CONCLUSION
This study demonstrates a profile of brain PET hypometabolism in long COVID patients with biologically confirmed SARS-CoV-2 and persistent functional complaints more than 3 weeks after the initial infection symptoms, involving the olfactory gyrus and connected limbic/paralimbic regions, extended to the brainstem and the cerebellum. These hypometabolisms are associated with patients' symptoms, with a biomarker value to identify and potentially follow these patients. The hypometabolism of the frontal cluster, which included the olfactory gyrus, seems to be linked to ACE drugs in patients with high blood pressure, with also a better metabolism of this olfactory region in patients using nasal decongestant spray, suggesting a possible role of ACE receptors as an olfactory gateway for this neurotropism.
Topics: Brain; COVID-19; Fluorodeoxyglucose F18; Humans; Positron-Emission Tomography; Retrospective Studies; SARS-CoV-2; Post-Acute COVID-19 Syndrome
PubMed: 33501506
DOI: 10.1007/s00259-021-05215-4 -
Frontiers in Neuroscience 2023Experiencing chronic stress significantly increases the risk for depression. Depression is a complex disorder with varied symptoms across patients. However, feeling of...
Experiencing chronic stress significantly increases the risk for depression. Depression is a complex disorder with varied symptoms across patients. However, feeling of sadness and decreased motivation, and diminished feeling of pleasure (anhedonia) appear to be core to most depressive pathology. Odorants are potent signals that serve a critical role in social interactions, avoiding danger, and consummatory behaviors. Diminished quality of olfactory function is associated with negative effects on quality of life leading to and aggravating the symptoms of depression. Odor hedonic value (I like or I dislike this smell) is a dominant feature of olfaction and guides approach or avoidance behavior of the odor source. The neural representation of the hedonic value of odorants is carried by the granule cells in the olfactory bulb, which functions to modulate the cortical relay of olfactory information. The granule cells of the olfactory bulb and those of the dentate gyrus are the two major populations of cells in the adult brain with continued neurogenesis into adulthood. In hippocampus, decreased neurogenesis has been linked to development or maintenance of depression symptoms. Here, we hypothesize that chronic mild stress can alter olfactory hedonics through effects on the olfactory bulb neurogenesis, contributing to the broader anhedonia phenotype in stress-associated depression. To test this, mice were subjected to chronic unpredictable mild stress and then tested on measures of depressive-like behaviors, odor hedonics, and measures of olfactory neurogenesis. Chronic unpredictable mild stress led to a selective effect on odor hedonics, diminishing attraction to pleasant but not unpleasant odorants, an effect that was accompanied by a specific decrease in adult neurogenesis and of the percentage of adult-born cells responding to pleasant odorants in the olfactory bulb.
PubMed: 37600017
DOI: 10.3389/fnins.2023.1224941