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Frontiers in Aging Neuroscience 2021To compare gray matter microstructural characteristics of higher-order olfactory regions among older adults with and without hyposmia. Data from the Brief Smell...
To compare gray matter microstructural characteristics of higher-order olfactory regions among older adults with and without hyposmia. Data from the Brief Smell Identification Test (BSIT) were obtained in 1998-99 for 265 dementia-free adults from the Health, Aging, and Body Composition study (age at BSIT: 74.9 ± 2.7; 62% White; 43% male) who received 3T diffusion tensor imaging in 2006-08 [Interval of time: mean (SD): 8.01 years (0.50)], Apolipoprotein (ApoEε4) genotypes, and repeated 3MS assessments until 2011-12. Cognitive status (mild cognitive impairment, dementia, normal cognition) was adjudicated in 2011-12. Hyposmia was defined as BSIT ≤ 8. Microstructural integrity was quantified by mean diffusivity (MD) in regions of the primary olfactory cortex amygdala, orbitofrontal cortex (including olfactory cortex, gyrus rectus, the orbital parts of the superior, middle, and inferior frontal gyri, medial orbital part of the superior frontal gyrus), and hippocampus. Multivariable regression models were adjusted for total brain atrophy, demographics, cognitive status, and ApoEε4 genotype. Hyposmia in 1998-99 ( = 57, 21.59%) was significantly associated with greater MD in 2006-08, specifically in the orbital part of the middle frontal gyrus, and amygdala, on the right [adjusted beta (p value): 0.414 (); 0.527 (); respectively]. Older adults with higher mean diffusivity in regions important for olfaction are more likely to have hyposmia up to ten years prior. Future studies should address whether hyposmia can serve as an early biomarker of brain microstructural abnormalities for older adults with a range of cognitive functions, including those with normal cognition.
PubMed: 34744681
DOI: 10.3389/fnagi.2021.648598 -
Neuroscience Research Sep 2022New neurons are constantly generated in the olfactory bulb and the dentate gyrus of the hippocampus. The number of new cells depends on sensory experiences; an enriched...
New neurons are constantly generated in the olfactory bulb and the dentate gyrus of the hippocampus. The number of new cells depends on sensory experiences; an enriched odor environment increases neurogenesis and neural survival. The aim of this study was to investigate whether enriched olfactory stimuli affect neurogenesis of mitral and granule cells of the olfactory bulb and dentate gyrus, and whether respiratory activity accompanied by olfactory stimuli is associated with new cells in these regions. To this end, respiratory activity during enriched odor stimuli was continuously measured in mice and new cells were stained with 5-bromo-2'-deoxyuridine, which selectively labels proliferating cells. An enriched olfactory environment significantly increased neurogenesis of mitral and granule cells in the olfactory bulb, but not in the dentate gyrus. Additionally, an increase of new granule cells under the enriched odor condition was correlated to sniffing frequency power, which had a significantly different pattern from the no-odor condition. A high respiratory frequency with frequent odor stimuli may be associated with activation of granule cells to form inhibitory neurons and this active state might increase granule cell neurogenesis.
Topics: Animals; Mice; Neurogenesis; Neurons; Odorants; Olfactory Bulb; Smell
PubMed: 35636589
DOI: 10.1016/j.neures.2022.05.007 -
NeuroImage Aug 2020MRI has been widely used to probe the neuroanatomy of the mouse brain, directly correlating MRI findings to histology is still challenging due to the limited spatial...
MRI has been widely used to probe the neuroanatomy of the mouse brain, directly correlating MRI findings to histology is still challenging due to the limited spatial resolution and various image contrasts derived from water relaxation or diffusion properties. Magnetic resonance histology has the potential to become an indispensable research tool to mitigate such challenges. In the present study, we acquired high spatial resolution MRI datasets, including diffusion MRI (dMRI) at 25 μm isotropic resolution and quantitative susceptibility mapping (QSM) at 21.5 μm isotropic resolution to validate with conventional mouse brain histology. Diffusion weighted images (DWIs) show better delineation of cortical layers and glomeruli in the olfactory bulb than fractional anisotropy (FA) maps. However, among all the image contrasts, including quantitative susceptibility mapping (QSM), T1/T2∗ images and DTI metrics, FA maps highlight unique laminar architecture in sub-regions of the hippocampus, including the strata of the dentate gyrus and CA fields of the hippocampus. The mean diffusivity (MD) and axial diffusivity (AD) yield higher correlation with DAPI (0.62 and 0.71) and NeuN (0.78 and 0.74) than with NF-160 (-0.34 and -0.49). The correlations between FA and DAPI, NeuN, and NF-160 are 0.31, -0.01, and -0.49, respectively. Our findings demonstrate that MRI at microscopic resolution deliver a three-dimensional, non-invasive and non-destructive platform for characterization of fine structural detail in both gray matter and white matter of the mouse brain.
Topics: Animals; Diffusion Magnetic Resonance Imaging; Diffusion Tensor Imaging; Gray Matter; Male; Mice; Mice, Inbred C57BL; White Matter
PubMed: 32344062
DOI: 10.1016/j.neuroimage.2020.116876 -
Brain Structure & Function Jan 2022Brain structural features of healthy individuals are associated with olfactory functions. However, due to the pathophysiological differences, congenital and acquired...
Brain structural features of healthy individuals are associated with olfactory functions. However, due to the pathophysiological differences, congenital and acquired anosmia may exhibit different structural characteristics. A systematic review was undertaken to compare brain structural features between patients with congenital and acquired anosmia. A systematic search was conducted using PubMed/MEDLINE and Scopus electronic databases to identify eligible reports on anosmia and structural changes and reported according to PRISMA guidelines. Reports were extracted for information on demographics, psychophysical evaluation, and structural changes. Then, the report was systematically reviewed based on various aetiologies of anosmia in relation to (1) olfactory bulb, (2) olfactory sulcus, (3) grey matter (GM), and white matter (WM) changes. Twenty-eight published studies were identified. All studies reported consistent findings with strong associations between olfactory bulb volume and olfactory function across etiologies. However, the association of olfactory function with olfactory sulcus depth was inconsistent. The present study observed morphological variations in GM and WM volume in congenital and acquired anosmia. In acquired anosmia, reduced olfactory function is associated with reduced volumes and thickness involving the gyrus rectus, medial orbitofrontal cortex, anterior cingulate cortex, and cerebellum. These findings contrast to those observed in congenital anosmia, where a reduced olfactory function is associated with a larger volume and higher thickness in parts of the olfactory network, including the piriform cortex, orbitofrontal cortex, and insula. The present review proposes that the structural characteristics in congenital and acquired anosmia are altered differently. The mechanisms behind these changes are likely to be multifactorial and involve the interaction with the environment.
Topics: Anosmia; Brain; Gray Matter; Humans; Magnetic Resonance Imaging; Olfaction Disorders
PubMed: 34635958
DOI: 10.1007/s00429-021-02397-3 -
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 -
Chemical Senses Jan 2022The brain forms robust associations between odors and emotionally salient memories, making odors especially effective at triggering fearful or traumatic memories. Using...
The brain forms robust associations between odors and emotionally salient memories, making odors especially effective at triggering fearful or traumatic memories. Using Pavlovian olfactory fear conditioning (OFC), a variant of the traditional tone-shock paradigm, this study explored the changes involved in its processing. We assessed the expression of neuronal plasticity markers phosphorylated cyclic adenosine monophosphate response element binding protein (pCREB) and phosphorylated mitogen-activated protein kinase (pMAPK) 24 h and 14 days following OFC, in newborn neurons (EdU+) and in brain regions associated with olfactory memory processing; the olfactory bulb, piriform cortex, amygdale, and hippocampus. Here, we show that all proliferating neurons in the dentate gyrus of the hippocampus and glomerular layer of the olfactory bulb were colocalized with pCREB at 24 h and 14 days post-conditioning, and the number of proliferating neurons at both time points were statistically similar. This suggests the occurrence of long-term potentiation within the neurons of this pathway. Finally, OFC significantly increased the density of pCREB- and pMAPK-positive immunoreactive neurons in the medial and cortical subnuclei of the amygdala and the posterior piriform cortex, suggesting their key involvement in its processing. Together, our investigation identifies changes in neuroplasticity within critical neural circuits responsible for olfactory fear memory.
Topics: Amygdala; Cell Proliferation; Fear; Humans; Infant, Newborn; Piriform Cortex; Smell
PubMed: 35997758
DOI: 10.1093/chemse/bjac021 -
The Journal of Neuroscience : the... Jan 2016Numerous clinical reports underscore the frequency of olfactory impairments in patients suffering from major depressive disorders (MDDs), yet the underlying...
UNLABELLED
Numerous clinical reports underscore the frequency of olfactory impairments in patients suffering from major depressive disorders (MDDs), yet the underlying physiopathological mechanisms remain poorly understood. We hypothesized that one key link between olfactory deficits and MDD lies in hypercortisolemia, a cardinal symptom of MDD. Corticosterone (CORT) is known to negatively correlate with hippocampal neurogenesis, yet its effects on olfactory neurogenesis and olfaction remain unknown. Here we used a rodent model of anxiety/depression-like states, which is based on chronic CORT administration and studied the effects of the antidepressant fluoxetine (FLX) on behavior, olfaction, and adult neurogenesis in the dentate gyrus (DG), olfactory bulb (OB), and the olfactory epithelium (OE). Chronic CORT had no effect on cell proliferation in the OE or on olfactory sensory neurons projecting to the OB, but induced pronounced deficits in olfactory acuity, fine discrimination of odorants and olfactory memory. These alterations were accompanied by a significant decrease in the number of adult-born neurons in both the DG and OB. Remarkably, FLX not only reversed depression-like states as expected, but also improved olfactory acuity, memory, and restored impaired adult neurogenesis. However, fine olfactory discrimination was not restored. Morphological analysis of adult-born neurons in both the DG and the OB showed that dendritic complexity was not significantly affected by CORT, but was increased by FLX. These findings demonstrate an essential role for glucocorticoids in triggering olfactory impairments in MDD and highlight a novel therapeutic effect of FLX.
SIGNIFICANCE STATEMENT
Increasing clinical reports show that major depression is characterized by pronounced olfactory deficits, yet the underlying mechanisms remain unknown. In this work, we used an endocrine model of depression to study whether hypothalamic-pituitary-adrenal axis perturbation could be sufficient to provoke olfactory impairments. We found that chronic corticosterone not only induces marked deficits in olfactory acuity, fine discrimination and olfactory memory, but also significantly decreases bulbar and hippocampal neurogenesis. Importantly, the antidepressant fluoxetine restores both adult neurogenesis and depressive states, and improves most olfactory functions. Our data reveal that impairment of hypothalamic-pituitary-adrenal axis during depression can lead to olfactory deficits and that the neurogenic effects of selective serotonin reuptake inhibitor antidepressants can successfully restore certain olfactory functions.
Topics: Animals; Anti-Inflammatory Agents; Antidepressive Agents, Second-Generation; Anxiety; Cell Proliferation; Corticosterone; Depression; Disease Models, Animal; Exploratory Behavior; Feeding Behavior; Fluoxetine; Grooming; Male; Mice; Mice, Inbred C57BL; Neurogenesis; Olfaction Disorders; Olfactory Mucosa; Olfactory Receptor Neurons; Reaction Time
PubMed: 26758842
DOI: 10.1523/JNEUROSCI.2817-15.2016 -
Frontiers in Neurology 2022Traumatic brain injury is one of the major causes of human olfactory dysfunction and leads to brain structure alterations, mainly in the cortical olfactory regions. Our...
OBJECTIVE
Traumatic brain injury is one of the major causes of human olfactory dysfunction and leads to brain structure alterations, mainly in the cortical olfactory regions. Our study aimed to investigate volume changes in the gray matter (GM) and white matter (WM) in patients with post-traumatic anosmia and then to explore the relationship between GM volume and olfactory function.
METHODS
Ethics committee approved prospective studies which included 22 patients with post-traumatic anosmia and 18 age- and gender-matched healthy volunteers. Olfactory function was assessed using the Sniffin' Sticks. High-resolution 3-dimensional T1 MRIs of the participants were acquired on a 3T scanner and the data were collected for voxel-based morphometry (VBM) analysis. Furthermore, the GM and WM volumes of the whole brain regions were compared and correlated with olfactory function.
RESULTS
The analysis revealed significant GM volume reduction in the orbitofrontal cortex (OFC), gyrus rectus (GR), olfactory cortex, insula, parahippocampal, temporal pole, and cerebellum (all < 0.001) in patients. Besides, WM volume loss was also found in the OFC, GR, and insula (all < 0.001) in patients. All WM atrophy areas were connected to areas of GM volume loss spatially. Correlation analysis showed the olfactory scores were significantly positively correlated with the GM volume of the occipital cortex ( < 0.001, and < 0.05), while no significant correlation was found between the Sniffin' Sticks test scores and the WM volume in patients.
CONCLUSION
The reduction of GM and WM volume in olfactory-related regions was responsible for olfactory dysfunction in post-traumatic patients. The occipital cortex may play a compensation mechanism to maintain the residual olfactory function. To our knowledge, we report here for the first time on white matter volume alterations specifically in post-traumatic patients with anosmia.
PubMed: 35860485
DOI: 10.3389/fneur.2022.690760 -
Frontiers in Cellular and Infection... 2022Ocular infection with causes toxoplasmosis in mice. However, following ocular infection with tachyzoites, the cause of the accompanying progressive changes in...
Ocular infection with causes toxoplasmosis in mice. However, following ocular infection with tachyzoites, the cause of the accompanying progressive changes in hippocampal-dependent tasks, and their relationship with the morphology and number of microglia, is less well understood. Here, in 6-month-old, female BALB/c mice, 5 μl of a suspension containing 48.5 × 10 tachyzoites/ml was introduced into the conjunctival sac; control received an equal volume of saline. Before and after instillation, all mice were subject to an olfactory discrimination (OD) test, using predator (cat) feces, and to an open-field (OF) task. After the behavioral tests, the animals were culled at either 22 or 44 days post-instillation (dpi), and the brains and retinas were dissected and processed for immunohistochemistry. The total number of Iba-1-immunolabeled microglia in the molecular layer of the dentate gyrus was estimated, and three-dimensional reconstructions of the cells were evaluated. Immobility was increased in the infected group at 12, 22, and 43 dpi, but the greatest immobility was observed at 22 dpi and was associated with reduced line crossing in the OF and distance traveled. In the OD test, infected animals spent more time in the compartment with feline fecal material at 14 and at 43 dpi. No OD changes were observed in the control group. The number of microglia was increased at 22 dpi but returned to control levels by 44 dpi. These changes were associated with the differentiation of tachyzoites into bradyzoite-enclosed cysts within the brain and retina. Thus, infection of mice with alters exploratory behavior, gives rise to a loss in predator's odor avoidance from 2 weeks after infection, increased microglia number, and altered their morphology in the molecular layer of the dentate gyrus.
Topics: Animals; Cats; Conjunctiva; Female; Mice; Mice, Inbred BALB C; Neuropathology; Toxoplasma; Toxoplasmosis, Animal
PubMed: 35372100
DOI: 10.3389/fcimb.2022.812152 -
Frontiers in Neuroscience 2016Adult neurogenesis is considered to contribute to a certain degree of plasticity for the brain. However, the effects of adult-born neurons on the brain are still largely...
Adult neurogenesis is considered to contribute to a certain degree of plasticity for the brain. However, the effects of adult-born neurons on the brain are still largely unknown. Here, we specifically altered the expression of miR-30c in the subventricular zone (SVZ) and dentate gyrus (DG) by stereotaxic injection with their respective up- and down-regulated lentiviruses. Results showed an increased level of miR-30c enhanced adult neurogenesis by prompting cell-cycles of stem cells, whereas down-regulated miR-30c led to the opposite results. When these effects of miR-30c lasted for 3 months, we detected significant morphological changes in the olfactory bulb (OB) and lineage alteration in the hippocampus. Tests of olfactory sensitivity and associative and spatial memory showed that a certain amount of adult-born neurons are essential for the normal functions of the OB and hippocampus, but there also exist redundant newborn neurons that do not further improve the functioning of these areas. Our study revealed the interactions between miRNA, adult neurogenesis, brain morphology and function, and this provides a novel insight into understanding the role of newborn neurons in the adult brain.
PubMed: 27242411
DOI: 10.3389/fnins.2016.00207