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Human Brain Mapping Jun 2018Removal of the olfactory bulb (OB) leads to depression like behavior in rodents. A link between depression and olfactory function is also established in humans. We...
BACKGROUND
Removal of the olfactory bulb (OB) leads to depression like behavior in rodents. A link between depression and olfactory function is also established in humans. We hypothesized that the human OB volume relates to depressive state and tested whether such a potential coherence is moderated by structural alterations in other brain regions.
METHODS
Eighty-three participants (32 patients with major depression and 51 matched healthy controls) underwent structural MR scanning. Individual OB volumes were compared between patients and controls and the impact of depression and comorbidity was analyzed with multiple regression analysis. Whole-brain voxel-based morphometry revealed structures co-varying with both depressive state and OB volume.
RESULTS
The OB volume of patients was significantly reduced and this reduction averaged out at 17% compared to the controls. The OB volume was correlated to the volume of the insula, superior temporal cortex, and amygdala. The independent variables of depression (β = -.37), age (β = -.25), and gender (β = -.40) explained the individual OB volume variation (R = .37). The correlation between OB volume and depression was moderated by volumetric reductions in a cluster including the insula and superior temporal gyrus (STG).
CONCLUSIONS
The OB volume relates to depression in humans and to the volume of structures which are critical for salience detection. We assume that a reduced OB volume causes diminished neural olfactory input which facilitates volume reduction in the insula and STG. The OB volume may hence constitute a factor of vulnerability to depression. Olfactory-based deep brain stimulation is discussed as a future therapeutic approach.
Topics: Adult; Analysis of Variance; Brain Mapping; Case-Control Studies; Depression; Female; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Olfactory Bulb; Regression Analysis; Surveys and Questionnaires
PubMed: 29493048
DOI: 10.1002/hbm.24024 -
PloS One 2018Severe hyposmia is a risk factor of dementia in Parkinson's disease (PD), while the underlying functional connectivity (FC) and brain volume alterations in PD patients...
OBJECTIVE
Severe hyposmia is a risk factor of dementia in Parkinson's disease (PD), while the underlying functional connectivity (FC) and brain volume alterations in PD patients with severe hyposmia (PD-SH) are unclear.
METHODS
We examined voxel-based morphometric and resting state functional magnetic resonance imaging findings in 15 cognitively normal PD-SH, 15 cognitively normal patients with PD with no/mild hyposmia (PD-N/MH), and 15 healthy controls (HCs).
RESULTS
Decreased gray matter volume (GMV) was observed in the bilateral cuneus, right associative visual area, precuneus, and some areas in anterior temporal lobes in PD-SH group compared to HCs. Both the PD-SH and PD-N/MH groups showed increased GMV in the bilateral posterior insula and its surrounding regions. A widespread significant decrease in amygdala FC beyond the decreased GMV areas and olfactory cortices were found in the PD-SH group compared with the HCs. Above all, decreased amygdala FC with the inferior parietal lobule, lingual gyrus, and fusiform gyrus was significantly correlated with both reduction of Addenbrooke's Cognitive Examination-Revised scores and severity of hyposmia in all participants. Canonical resting state networks exhibited decreased FC in the precuneus and left executive control networks but increased FC in the primary and high visual networks of patients with PD compared with HCs. Canonical network FC to other brain regions was enhanced in the executive control, salience, primary visual, and visuospatial networks of the PD-SH.
CONCLUSION
PD-SH showed extensive decreased amygdala FC. Particularly, decreased FC between the amygdala and inferior parietal lobule, lingual gyrus, and fusiform gyrus were associated with the severity of hyposmia and cognitive performance. In contrast, relatively preserved canonical networks in combination with increased FC to brain regions outside of canonical networks may be related to compensatory mechanisms, and preservation of brain function.
Topics: Aged; Brain Mapping; Cognition; Female; Gray Matter; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Olfaction Disorders; Parkinson Disease
PubMed: 29304050
DOI: 10.1371/journal.pone.0190072 -
Frontiers in Aging Neuroscience 2021To explore the relationship between white matter changes and olfactory ability among patients with mild cognitive impairment (MCI) and to develop a tool to predict the...
To explore the relationship between white matter changes and olfactory ability among patients with mild cognitive impairment (MCI) and to develop a tool to predict the development of Alzheimer's disease among patients with MCI. The Montreal Cognitive Assessment (MoCA) was used for cognitive assessments, and the 70% isopropanol test paper was used to evaluate olfactory function. Tract-based spatial statistics, based on the diffusion tensor imaging technology, were used to obtain relevant parameters, and behavioral and imaging results were compared between patients with MCI ( = 36) and healthy older adults ( = 32). The olfactory ability of MCI patients was lower overall, which was positively correlated with the MoCA score. Fractional anisotropy (FA) changes significantly of all parameters. Lower FA regions were mainly located in the corpus callosum, the orbitofrontal gyrus, and the left occipital lobe. The olfactory score was significantly correlated with the FA value of the orbitofrontal gyrus. Fibrous connections in several brain regions, such as the entorhinal cortex, were stronger in patients with MCI. The olfactory ability of MCI patients in our group was positively correlated with the neuropsychological scale results. Impairment in olfactory function was superior to memory deficits for predicting cognitive decline among cognitively intact participants. The fibrous connections in several brain regions, such as the entorhinal cortex, were higher in patients with MCI, which suggested that there may be a compensatory mechanism in the olfactory pathway in MCI patients. The decline in olfactory function may be a significant and useful indicator of neuropathological changes in MCI patients and an effective marker for the development of cognitive decline and dementia.
PubMed: 34887745
DOI: 10.3389/fnagi.2021.765432 -
EClinicalMedicine Aug 2020Increasing evidence supported the possible neuro-invasion potential of SARS-CoV-2. However, no studies were conducted to explore the existence of the micro-structural...
BACKGROUND
Increasing evidence supported the possible neuro-invasion potential of SARS-CoV-2. However, no studies were conducted to explore the existence of the micro-structural changes in the central nervous system after infection. We aimed to identify the existence of potential brain micro-structural changes related to SARS-CoV-2.
METHODS
In this prospective study, diffusion tensor imaging (DTI) and 3D high-resolution T1WI sequences were acquired in 60 recovered COVID-19 patients (56.67% male; age: 44.10 ± 16.00) and 39 age- and sex-matched non-COVID-19 controls (56.41% male; age: 45.88 ± 13.90). Registered fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were quantified for DTI, and an index score system was introduced. Regional volumes derived from Voxel-based Morphometry (VBM) and DTI metrics were compared using analysis of covariance (ANCOVA). Two sample t-test and Spearman correlation were conducted to assess the relationships among imaging indices, index scores and clinical information.
FINDINGS
In this follow-up stage, neurological symptoms were presented in 55% COVID-19 patients. COVID-19 patients had statistically significantly higher bilateral gray matter volumes (GMV) in olfactory cortices, hippocampi, insulas, left Rolandic operculum, left Heschl's gyrus and right cingulate gyrus and a general decline of MD, AD, RD accompanied with an increase of FA in white matter, especially AD in the right CR, EC and SFF, and MD in SFF compared with non-COVID-19 volunteers (corrected value <0.05). Global GMV, GMVs in left Rolandic operculum, right cingulate, bilateral hippocampi, left Heschl's gyrus, and Global MD of WM were found to correlate with memory loss ( value <0.05). GMVs in the right cingulate gyrus and left hippocampus were related to smell loss ( value <0.05). MD-GM score, global GMV, and GMV in right cingulate gyrus were correlated with LDH level ( value <0.05).
INTERPRETATION
Study findings revealed possible disruption to micro-structural and functional brain integrity in the recovery stages of COVID-19, suggesting the long-term consequences of SARS-CoV-2.
FUNDING
Shanghai Natural Science Foundation, Youth Program of National Natural Science Foundation of China, Shanghai Sailing Program, Shanghai Science and Technology Development, Shanghai Municipal Science and Technology Major Project and ZJ Lab.
PubMed: 32838240
DOI: 10.1016/j.eclinm.2020.100484 -
Diabetes, Metabolic Syndrome and... 2021The purpose of the study was to find the differences in intrinsic functional connectivity (FC) patterns of the primary visual area (V1) among diabetic retinopathy (DR),...
OBJECTIVE
The purpose of the study was to find the differences in intrinsic functional connectivity (FC) patterns of the primary visual area (V1) among diabetic retinopathy (DR), diabetes mellitus (DM), and healthy controls (HCs) applying resting-state functional magnetic resonance imaging (rs-fMRI).
PATIENTS AND METHODS
Thirty-five subjects with DR (18 males and 17 females), 22 DM (10 males and 12 females) and 38 HCs (16 males and 22 females) matched for sex, age, and education underwent rs-fMRI scanning. Seed-based FC analysis was performed to find the alterations in the intrinsic FC patterns of V1 in DR compared with DM and HCs.
RESULTS
The study found that DR patients had a significant lower FC between the bilateral calcarine (CAL)/left lingual gyrus (LING) (BA 17/18) and the left V1, and between the bilateral CAL/left LING (BA 17/18) and the right V1 compared with the HCs. Meanwhile, patients with DR exhibited higher FC strength between the left V1 and the bilateral Caudate/Olfactory/Orbital superior frontal gyrus (OSFG), and between the bilateral Caudate/Olfactory/OSFG (BA 3/4/6) and the right V1. Compared with DM group, patients with DR showed increased FC strength between the right CAL (BA 17/18) and the right V1. DM group exhibited lower FC strength between the left fusiform and the left V1, and between the bilateral CAL and the right V1 when compared with HCs. Moreover, DM group was observed to have higher FC strength between the left superior frontal gyrus and the left V1.
CONCLUSION
Our findings indicated that DR patients exhibited FC disruptions between V1 and higher visual regions at rest, which may reflect the aberrant information communication in the V1 area of DR individuals. The findings offer important insights into the neuromechanism of vision disorder in DR patients.
PubMed: 34285528
DOI: 10.2147/DMSO.S311009 -
BMC Neuroscience Mar 2021Alzheimer's disease (AD) is characterized by cognitive impairment that eventually develops into dementia. Amyloid-beta (Aβ) accumulation is a widely described hallmark...
BACKGROUND
Alzheimer's disease (AD) is characterized by cognitive impairment that eventually develops into dementia. Amyloid-beta (Aβ) accumulation is a widely described hallmark in AD, and has been reported to cause olfactory dysfunction, a condition considered an early marker of the disease associated with injuries in the olfactory bulb (OB), the hippocampus (HIPP) and other odor-related cortexes. Adiponectin (APN) is an adipokine with neuroprotective effects. Studies have demonstrated that APN administration decreases Aβ neurotoxicity and Tau hyperphosphorylation in the HIPP, reducing cognitive impairment. However, there are no studies regarding the neuroprotective effects of APN in the olfactory dysfunction observed in the Aβ rat model. The aim of the present study is to determine whether the intracerebroventricular (i.c.v) administration of APN prevents the early olfactory dysfunction in an i.c.v Amyloid-beta (Aβ) rat model. Hence, we evaluated olfactory function by using a battery of olfactory tests aimed to assess olfactory memory, discrimination and detection in the Aβ rat model treated with APN. In addition, we determined the number of cells expressing the neuronal nuclei (NeuN), as well as the number of microglial cells by using the ionized calcium-binding adapter molecule 1 (Iba-1) marker in the OB and, CA1, CA3, hilus and dentate gyrus (DG) in the HIPP. Finally, we determined Arginase-1 expression in both nuclei through Western blot.
RESULTS
We observed that the i.c.v injection of Aβ decreased olfactory function, which was prevented by the i.c.v administration of APN. In accordance with the olfactory impairment observed in i.c.v Aβ-treated rats, we observed a decrease in NeuN expressing cells in the glomerular layer of the OB, which was also prevented with the i.c.v APN. Furthermore, we observed an increase of Iba-1 cells in CA1, and DG in the HIPP of the Aβ rats, which was prevented by the APN treatment.
CONCLUSION
The present study describes the olfactory impairment of Aβ treated rats and evidences the protective role that APN plays in the brain, by preventing the olfactory impairment induced by Aβ. These results may lead to APN-based pharmacological therapies aimed to ameliorate AD neurotoxic effects.
Topics: Adiponectin; Alzheimer Disease; Amyloid beta-Peptides; Animals; Brain; Disease Models, Animal; Injections, Intraventricular; Male; Neuroprotective Agents; Olfaction Disorders; Rats; Rats, Wistar
PubMed: 33653273
DOI: 10.1186/s12868-021-00620-9 -
Annals of Clinical and Translational... Feb 2023This research aims to study structural brain changes in patients with persistent olfactory dysfunctions after coronavirus disease 2019 (COVID-19).
OBJECTIVE
This research aims to study structural brain changes in patients with persistent olfactory dysfunctions after coronavirus disease 2019 (COVID-19).
METHODS
COVID-19 patients were evaluated using T1-weighted and diffusion tensor imaging (DTI) on a 3T MRI scanner, 9.94 ± 3.83 months after COVID-19 diagnosis. Gray matter (GM) voxel-based morphometry was performed using FSL-VBM. Voxelwise statistical analysis of the fractional anisotropy, mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity was carried out with the tract-based spatial statistics in the olfactory system. The smell identification test (UPSIT) was used to classify patients as normal olfaction or olfactory dysfunction groups. Intergroup comparisons between GM and DTI measures were computed, as well as correlations with the UPSIT scores.
RESULTS
Forty-eight COVID-19 patients were included in the study. Twenty-three were classified as olfactory dysfunction, and 25 as normal olfaction. The olfactory dysfunction group had lower GM volume in a cluster involving the left amygdala, insular cortex, parahippocampal gyrus, frontal superior and inferior orbital gyri, gyrus rectus, olfactory cortex, caudate, and putamen. This group also showed higher MD values in the genu of the corpus callosum, the orbitofrontal area, the anterior thalamic radiation, and the forceps minor; and higher RD values in the anterior corona radiata, the genu of the corpus callosum, and uncinate fasciculus compared with the normal olfaction group. The UPSIT scores for the whole sample were negatively associated with both MD and RD values (p-value ≤0.05 FWE-corrected).
INTERPRETATION
There is decreased GM volume and increased MD in olfactory-related regions explaining prolonged olfactory deficits in post-acute COVID-19 patients.
Topics: Humans; Smell; Diffusion Tensor Imaging; COVID-19 Testing; COVID-19; Brain; Olfaction Disorders
PubMed: 36525472
DOI: 10.1002/acn3.51710 -
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 -
International Journal of Molecular... May 2022The aim of this study was to illustrate recent developments in neural repair utilizing hyaluronan as a carrier of olfactory bulb stem cells and in new bioscaffolds to... (Review)
Review
The aim of this study was to illustrate recent developments in neural repair utilizing hyaluronan as a carrier of olfactory bulb stem cells and in new bioscaffolds to promote neural repair. Hyaluronan interacts with brain hyalectan proteoglycans in protective structures around neurons in perineuronal nets, which also have roles in the synaptic plasticity and development of neuronal cognitive properties. Specialist stem cell niches termed fractones located in the sub-ventricular and sub-granular regions of the dentate gyrus of the hippocampus migrate to the olfactory bulb, which acts as a reserve of neuroprogenitor cells in the adult brain. The extracellular matrix associated with the fractone stem cell niche contains hyaluronan, perlecan and laminin α5, which regulate the quiescent recycling of stem cells and also provide a means of escaping to undergo the proliferation and differentiation to a pluripotent migratory progenitor cell type that can participate in repair processes in neural tissues. Significant improvement in the repair of spinal cord injury and brain trauma has been reported using this approach. FGF-2 sequestered by perlecan in the neuroprogenitor niche environment aids in these processes. Therapeutic procedures have been developed using olfactory ensheathing stem cells and hyaluronan as a carrier to promote neural repair processes. Now that recombinant perlecan domain I and domain V are available, strategies may also be expected in the near future using these to further promote neural repair strategies.
Topics: Cell Differentiation; Extracellular Matrix; Hyaluronic Acid; Neurogenesis; Neurons; Stem Cell Niche
PubMed: 35563536
DOI: 10.3390/ijms23095148 -
The Journal of Neuroscience : the... Nov 2023It is known that humans and rodents are capable of transmitting stress to their naive partners via social interaction. However, a comprehensive understanding of...
It is known that humans and rodents are capable of transmitting stress to their naive partners via social interaction. However, a comprehensive understanding of transmitted stress, which may differ from authentic stress, thus revealing unique neural mechanisms of social interaction resulting from transmitted stress and the associated anxiety, is missing. We used, in the present study, maternal separation (MS) as a stress model to investigate whether MS causes abnormal behavior in adolescence. A key concern in the analysis of stress transmission is whether the littermates of MS mice who only witness MS stress ("Partners") exhibit behavioral abnormalities similar to those of MS mice themselves. Of special interest is the establishment of the neural mechanisms underlying transmitted stress and authentic stress. The results show that Partners, similar to MS mice, exhibit anxiety-like behavior and hyperalgesia after witnessing littermates being subjected to early-life repetitive MS. Electrophysiological analysis revealed that mice subjected to MS demonstrate a reduction in both the excitatory and inhibitory synaptic activities of parvalbumin interneurons (PVINs) in the anterior cingulate cortex (ACC). However, Partners differed from MS mice in showing an increase in the number and excitability of GABAergic PVINs in the ACC and in the ability of chemogenetic PVIN inactivation to eliminate abnormal behavior. Furthermore, the social transfer of anxiety-like behavior required intact olfactory, but not visual, perception. This study suggests a functional involvement of ACC PVINs in mediating the distinct neural basis of transmitted anxiety. The anterior cingulate cortex (ACC) is a critical brain area in physical and social pain and contributes to the exhibition of abnormal behavior. ACC glutamatergic neurons have been shown to encode transmitted stress, but it remains unclear whether inhibitory ACC neurons also play a role. We evaluate, in this study, ACC neuronal, synaptic and network activities and uncover a critical role of parvalbumin interneurons (PVINs) in the expression of transmitted stress in adolescent mice who had witnessed MS of littermates in infancy. Furthermore, inactivation of ACC PVINs blocks transmitted stress. The results suggest that emotional contagion has a severe effect on brain function, and identify a potential target for the treatment of transmitted anxiety.
Topics: Humans; Mice; Animals; Gyrus Cinguli; Parvalbumins; Maternal Deprivation; Neurons; Anxiety
PubMed: 37845036
DOI: 10.1523/JNEUROSCI.0558-23.2023