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BioRxiv : the Preprint Server For... Mar 2023The postnatal neural stem cell (NSC) pool hosts quiescent and activated radial glia-like NSCs contributing to neurogenesis throughout adulthood. However, the underlying...
The postnatal neural stem cell (NSC) pool hosts quiescent and activated radial glia-like NSCs contributing to neurogenesis throughout adulthood. However, the underlying regulatory mechanism during the transition from quiescent NSCs to activated NSCs in the postnatal NSC niche is not fully understood. Lipid metabolism and lipid composition play important roles in regulating NSC fate determination. Biological lipid membranes define the individual cellular shape and help maintain cellular organization and are highly heterogenous in structure and there exist diverse microdomains (also known as lipid rafts), which are enriched with sugar molecules, such as glycosphingolipids. An often overlooked but key aspect is that the functional activities of proteins and genes are highly dependent upon their molecular environments. We previously reported that ganglioside GD3 is the predominant species in NSCs and that the reduced postnatal NSC pools are observed in global GD3-synthase knockout (GD3S-KO) mouse brains. The specific roles of GD3 in determining the stage and cell-lineage determination of NSCs remain unclear, since global GD3S-KO mice cannot distinguish if GD3 regulates postnatal neurogenesis or developmental impacts. Here we show that inducible GD3 deletion in postnatal radial glia-like NSCs promotes the NSC activation, resulting in the loss of the long-term maintenance of the adult NSC pools. The reduced neurogenesis in the subventricular zone (SVZ) and the dentate gyrus (DG) of GD3S-conditional-knockout mice led to impaired olfactory and memory functions. Thus, our results provide convincing evidence that postnatal GD3 maintains the quiescent state of radial glia-like NSCs in the adult NSC niche.
PubMed: 36993675
DOI: 10.1101/2023.03.14.532547 -
Brain Sciences Mar 2023It is crucial to understand the neural feedback mechanisms and the cognitive decision-making of the brain during the processing of rewards. Here, we report the first...
BACKGROUND
It is crucial to understand the neural feedback mechanisms and the cognitive decision-making of the brain during the processing of rewards. Here, we report the first attempt for a simultaneous electroencephalography (EEG)-functional magnetic resonance imaging (fMRI) study in a gambling task by utilizing tensor decomposition.
METHODS
First, the single-subject EEG data are represented as a third-order spectrogram tensor to extract frequency features. Next, the EEG and fMRI data are jointly decomposed into a superposition of multiple sources characterized by space-time-frequency profiles using coupled matrix tensor factorization (CMTF). Finally, graph-structured clustering is used to select the most appropriate model according to four quantitative indices.
RESULTS
The results clearly show that not only are the regions of interest (ROIs) found in other literature activated, but also the olfactory cortex and fusiform gyrus which are usually ignored. It is found that regions including the orbitofrontal cortex and insula are activated for both winning and losing stimuli. Meanwhile, regions such as the superior orbital frontal gyrus and anterior cingulate cortex are activated upon winning stimuli, whereas the inferior frontal gyrus, cingulate cortex, and medial superior frontal gyrus are activated upon losing stimuli.
CONCLUSION
This work sheds light on the reward-processing progress, provides a deeper understanding of brain function, and opens a new avenue in the investigation of neurovascular coupling via CMTF.
PubMed: 36979295
DOI: 10.3390/brainsci13030485 -
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 -
Molecular Neurobiology Jun 2023Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting the body and mind of millions of people in the world. As PD progresses,...
Restoration of Adult Neurogenesis by Intranasal Administration of Gangliosides GD3 and GM1 in The Olfactory Bulb of A53T Alpha-Synuclein-Expressing Parkinson's-Disease Model Mice.
Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting the body and mind of millions of people in the world. As PD progresses, bradykinesia, rigidity, and tremor worsen. These motor symptoms are associated with the neurodegeneration of dopaminergic neurons in the substantia nigra. PD is also associated with non-motor symptoms, including loss of smell (hyposmia), sleep disturbances, depression, anxiety, and cognitive impairment. This broad spectrum of non-motor symptoms is in part due to olfactory and hippocampal dysfunctions. These non-motor functions are suggested to be linked with adult neurogenesis. We have reported that ganglioside GD3 is required to maintain the neural stem cell (NSC) pool in the subventricular zone (SVZ) of the lateral ventricles and the subgranular layer of the dentate gyrus (DG) in the hippocampus. In this study, we used nasal infusion of GD3 to restore impaired neurogenesis in A53T alpha-synuclein-expressing mice (A53T mice). Intriguingly, intranasal GD3 administration rescued the number of bromodeoxyuridine + (BrdU +)/Sox2 + NSCs in the SVZ. Furthermore, the administration of gangliosides GD3 and GM1 increases doublecortin (DCX)-expressing immature neurons in the olfactory bulb, and nasal ganglioside administration recovered the neuronal populations in the periglomerular layer of A53T mice. Given the relevance of decreased ganglioside on olfactory impairment, we discovered that GD3 has an essential role in olfactory functions. Our results demonstrated that intranasal GD3 infusion restored the self-renewal ability of the NSCs, and intranasal GM1 infusion promoted neurogenesis in the adult brain. Using a combination of GD3 and GM1 has the potential to slow down disease progression and rescue dysfunctional neurons in neurodegenerative brains.
Topics: Mice; Animals; alpha-Synuclein; Parkinson Disease; G(M1) Ganglioside; Olfactory Bulb; Administration, Intranasal; Gangliosides; Neurogenesis; Dopaminergic Neurons
PubMed: 36849668
DOI: 10.1007/s12035-023-03282-2 -
Brazilian Journal of Otorhinolaryngology 2023The aim of this study was to examine the changes in gray matter in nasopharyngeal carcinoma patients with normal hearing (Group 1) and nasopharyngeal carcinoma patients...
OBJECTIVES
The aim of this study was to examine the changes in gray matter in nasopharyngeal carcinoma patients with normal hearing (Group 1) and nasopharyngeal carcinoma patients with hearing loss (Group 2) after radiotherapy using voxel-based morphological analysis and to analyze the relationship with the radiation doses of the temporal lobe.
METHODS
21 patients in Group 1, 14 patients in Group 2, and 21 healthy volunteers were selected. All participants underwent an otologic examination and three-dimensional magnetization preparatory rapid acquisition gradient echo sequence scan. The correlation between the variation of whole brain gray matter volume and the doses of the temporal lobe was analyzed by Data Processing & Analysis for Brain Imaging software.
RESULTS
Compared with the normal control group, the brain areas with reduced gray matter volume in nasopharyngeal carcinoma patients after radiotherapy were mainly in the left posterior cerebellar lobe (T = -8.797), left insular lobe (T = -7.96), and the right insular lobe (T = -6.632). Compared to Group 1, the brain areas of Group 2 patients with reduced gray matter volume were mainly in the left superior temporal gyrus (T = -2.366), left olfactory bulb (T = -2.52), left Rolandic operculum (T = -2.431), and right olfactory bulb (T = -3.100). Compared with Group 1, the brain areas of Group 2 patients with increased gray matter volume were mainly in the left calcarine sulcus (T=3.425) and right calcarine sulcus (T=3.169). There were no correlations between the changes of brain gray matter volume and the radiation doses of the temporal lobe in both Group 1 and Group 2.
CONCLUSIONS
The radiotherapy may cause the changes of brain areas associated with cognitive function in nasopharyngeal carcinoma in a long-term follow-up. At the same time, nasopharyngeal carcinoma patients with the radiation-induced hearing loss had abnormal gray matter volumes in the auditory center and other sensory centers. Our findings might provide new understanding into the pathogenesis of radiation-induced brain damage in normal-appearing brain tissue. Yet this exploratory study should be taken with caution.
Topics: Humans; Gray Matter; Nasopharyngeal Carcinoma; Follow-Up Studies; Brain; Magnetic Resonance Imaging; Hearing Loss; Nasopharyngeal Neoplasms
PubMed: 36805347
DOI: 10.1016/j.bjorl.2023.01.005 -
Research Square Jan 2023Sex is an important contributing factor to neuroimaging phenotypes in brain disorders. However, little is known about the contribution of sex differences to the...
BACKGROUND AND OBJECTIVES
Sex is an important contributing factor to neuroimaging phenotypes in brain disorders. However, little is known about the contribution of sex differences to the neurodegeneration in dementia with Lewy bodies (DLB). We investigated sex differences in probable DLB patients by using both visual rating scales of lobar atrophy and automated estimations of regional atrophy.
METHODS
We included 442 probable DLB patients from the European-DLB consortium and the Mayo Clinic who have magnetic resonance imaging (MRI) data available. We assessed sex differences and the sex-by-age interaction in two largely independent samples through visual rating scales of lobar atrophy (n = 333; mean age 73 ± 8 years, 62% males) and automated regional estimations of gray matter (GM) volume and mean cortical thickness (CTh) (n = 165; mean age 69 ± 9 years, 72% males). We used binary logistic regression and ANOVA for statistical analysis.
RESULTS
We found a statistically significantly higher likelihood of frontal atrophy measured by the global cortical atrophy-frontal subscale (GCA-F) in males (40% of males had an abnormal GCA-F score versus 29% of females, -value = 0.006). Using automated estimations, we found smaller GM volumes in 6 cortical regions in males compared with females, as well as smaller GM volume in the entorhinal cortex and thinner olfactory cortices in females, compared with males. The sex-by-age interaction showed statistically significant results in 6 cortical volumes and 7 mean CTh estimations (-value ≤ 0.05), accentuated in the right middle frontal gyrus (FDR-adjusted -value = 0.047). These cross-sectional interactions indicated that while females have statistically significantly less atrophy than males at younger ages, differences become non-significant at older ages, with females showing the same level of atrophy than males around the age of 75.
CONCLUSIONS
This study demonstrates sex differences on brain atrophy in probable DLB. While male DLB patients have a more widespread pattern of cortical atrophy at younger ages, these sex differences tend to disappear with increasing age. Longitudinal studies will help establish these cross-sectional findings and inform on sex and age considerations to the use of MRI in clinical routine, as the field moves towards precision medicine.
PubMed: 36747755
DOI: 10.21203/rs.3.rs-2516427/v1 -
NeuroImage Apr 2023[F]fluoroetoxybenzovesamicol ([F]FEOBV) is a positron emission topography (PET) tracer for the vesicular acetylcholine transporter (VAChT), a protein located...
INTRODUCTION
[F]fluoroetoxybenzovesamicol ([F]FEOBV) is a positron emission topography (PET) tracer for the vesicular acetylcholine transporter (VAChT), a protein located predominantly in synaptic vesicles in cholinergic nerve terminals. We aimed to use [F]FEOBV PET to study the cholinergic topography of the healthy human brain.
MATERIALS AND METHODS
[F]FEOBV PET brain data volumes of healthy elderly humans were normalized to standard space and intensity-normalized to the white matter. Stereotactic atlases of regions of interest were superimposed to describe and quantify tracer distribution. The spatial distribution of [F]FEOBV PET uptake was compared with histological and gene expression data.
RESULTS
Twenty participants of both sexes and a mean age of 73.9 ± 6.0 years, age-range [64; 86], were recruited. Highest tracer binding was present in the striatum, some thalamic nuclei, and the basal forebrain. Intermediate binding was found in most nuclei of the brainstem, thalamus, and hypothalamus; the vermis and flocculonodular lobe; and the hippocampus, amygdala, insula, cingulate, olfactory cortex, and Heschl's gyrus. Lowest binding was present in most areas of the cerebral cortex, and in the cerebellar nuclei and hemispheres. The spatial distribution of tracer correlated with immunohistochemical post-mortem data, as well as with regional expression levels of SLC18A3, the VAChT coding gene.
DISCUSSION
Our in vivo findings confirm the regional cholinergic distribution in specific brain structures as described post-mortem. A positive spatial correlation between tracer distribution and regional gene expression levels further corroborates [F]FEOBV PET as a validated tool for in vivo cholinergic imaging. The study represents an advancement in the continued efforts to delineate the spatial topography of the human cholinergic system in vivo.
Topics: Aged; Female; Humans; Male; Middle Aged; Brain; Cholinergic Agents; Electrons; Piperidines; Positron-Emission Tomography; Vesicular Acetylcholine Transport Proteins; Fluorine Radioisotopes
PubMed: 36720436
DOI: 10.1016/j.neuroimage.2023.119908 -
Chemical Senses Jan 2023Little is known about the neural basis of lower- and higher-order olfactory functions such as odor memory, compared with other sensory systems. The aim of this study was...
Little is known about the neural basis of lower- and higher-order olfactory functions such as odor memory, compared with other sensory systems. The aim of this study was to explore neural networks and correlates associated with 3 functions: passive smelling (PS), odor encoding (OE), and in particular odor recognition memory (ORM). Twenty-six healthy participants were examined using functional magnetic resonance imaging conducted across 3 sessions, one for each function. Independent component analysis revealed a difference between sessions where a distinct ORM component incorporating hippocampus and posterior cingulate showed delayed triggering dissociated from odor stimulation and recognition. By contrasting Hit for ORM (target odors correctly recognized as old) and a combination of PS and detected odors from OE, we found significantly lower activations in amygdala, piriform cortex, insula, thalamus, and the inferior parietal lobule. Region of interest analysis including anterior insula, posterior cingulate gyrus, dentate gyrus, left middle frontal gyrus, amygdala, and piriform cortex demonstrated that Hit were associated with lower activations compared with other memory responses. In summary, our findings suggest that successful recognition of familiar odors (odor familiarity) is associated with neural suppression in the abovementioned regions of interest. Additionally, network including the hippocampus and posterior cingulate is engaged in a postrecognition process. This process may be related to incidental encoding of less familiar and more novel odors (odor novelty) and should be subject for future research.
Topics: Humans; Odorants; Smell; Recognition, Psychology; Hippocampus; Amygdala; Magnetic Resonance Imaging; Brain; Brain Mapping
PubMed: 36715106
DOI: 10.1093/chemse/bjad001 -
Frontiers in Allergy 2022Currently, clinical assessment of olfaction is largely reliant on subjective methods that require patient participation. The objective method for measuring olfaction,...
IMPORTANCE
Currently, clinical assessment of olfaction is largely reliant on subjective methods that require patient participation. The objective method for measuring olfaction, using electroencephalogram (EEG) readings, can be supplemented with the improved temporal resolution of magnetoencephalography (MEG) for olfactory measurement that can delineate cortical and peripheral olfactory loss. MEG provides high temporal and spatial resolution which can enhance our understanding of central olfactory processing compared to using EEG alone.
OBJECTIVE
To determine the feasibility of building an in-house portable olfactory stimulator paired with electrophysiological neuroimaging technique with MEG to assess olfaction in the clinical setting.
DESIGN SETTING AND PARTICIPANTS
This proof-of-concept study utilized a paired MEG-olfactometer paradigm to assess olfaction in three normosmic participants. We used a two-channel olfactory stimulator to deliver odorants according to a programmed stimulus-rest paradigm. Two synthetic odorants: 2% phenethyl alcohol (rose) and 0.5% amyl acetate (banana) were delivered in increasing increments of time followed by periods of rest. Cortical activity was measured a 306-channel MEG system.
MAIN OUTCOMES AND MEASURES
Primary outcome measure was the relative spectral power for each frequency band, which was contrasted between rest and olfactory stimulation.
RESULTS
Compared to rest, olfactory stimulation produced a 40% increase in relative alpha power within the olfactory cortex bilaterally with both odorants. A 25%-30% increase in relative alpha power occurred in the left orbitofrontal cortex and precentral gyrus with phenethyl alcohol stimulation but not amyl acetate.
CONCLUSION AND RELEVANCE
In this proof-of-concept study, we demonstrate the feasibility of olfactory measurement an olfactometer-MEG paradigm. We found that odorant-specific cortical signatures can be identified using this paradigm, setting the basis for further investigation of this system as a prognostic tool for olfactory loss.
PubMed: 36698377
DOI: 10.3389/falgy.2022.1019265