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  • 1
    Online Resource
    Online Resource
    In Vivo Cerebral Translocator Protein (TSPO) Binding and Its Relationship with Blood Adiponectin Levels in Treatment-Naïve Young Adults with Major Depression: A [11C]PK11195 PET Study
    MDPI AG ; 2021
    In:  Biomedicines Vol. 10, No. 1 ( 2021-12-24), p. 34-
    Details
    In: Biomedicines, MDPI AG, Vol. 10, No. 1 ( 2021-12-24), p. 34-
    Abstract: Adiponectin is an adipokine that mediates cellular cholesterol efflux and plays important roles in neuroinflammatory processes. In this study, we undertook positron emission tomography (PET) with the translocator protein (TSPO) ligand [11C]PK11195 and measured serum adiponectin levels in groups of treatment-naïve young adult patients with major depressive disorder (MDD) and matched healthy controls. Thirty treatment-naïve MDD patients (median age: 24 years) and twenty-three healthy controls underwent [11C] PK11195 PET. We quantified TSPO availability in brain as the [11C]PK11195 binding potential (BPND) using a reference tissue model in conjunction with the supervised cluster analysis (SVCA4) algorithm. Age, sex distribution, body mass index, and serum adiponectin levels did not differ between the groups. Between-group analysis using a region-of-interest approach showed significantly higher [11C] PK11195 BPND in the left anterior and right posterior cingulate cortices in MDD patients than in controls. Serum adiponectin levels had significant negative correlations with [11C]PK11195 BPND in the bilateral hippocampus in MDD patients, but significant positive correlations in the bilateral hippocampus in the control group. Our results indicate significantly higher TSPO binding in the anterior and posterior cingulate cortices in treatment-naïve young MDD patients, suggesting microglial activation in these limbic regions, which are involved in cognitive and emotional processing. The opposite correlations between [11C] PK11195 BPND in the hippocampus with serum adiponectin levels in MDD and control groups suggest that microglial activation in the hippocampus may respond differentially to adiponectin signaling in MDD and healthy subjects, possibly with respect to microglial phenotype.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    URL: Article
    DOI: 10.3390/biomedicines10010034
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2720867-9
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  • 2
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    Online Resource
    In vivo glucose metabolism and glutamate levels in mGluR5 knockout mice: a multimodal neuroimaging study using [18F]FDG microPET and MRS
    Springer Science and Business Media LLC ; 2020
    In:  EJNMMI Research Vol. 10, No. 1 ( 2020-12)
    Details
    In: EJNMMI Research, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2020-12)
    Abstract: Perturbed functional coupling between the metabotropic glutamate receptor-5 (mGluR5) and N-methyl- d -aspartate (NMDA) receptor-mediated excitatory glutamatergic neurotransmission may contribute to the pathophysiology of psychiatric disorders such as schizophrenia. We aimed to establish the functional interaction between mGluR5 and NMDA receptors in brain of mice with genetic ablation of the mGluR5. Methods We first measured the brain glutamate levels with magnetic resonance spectroscopy (MRS) in mGluR5 knockout (KO) and wild-type (WT) mice. Then, we assessed brain glucose metabolism with [ 18 F]fluorodeoxyglucose ([ 18 F]FDG) positron emission tomography before and after the acute administration of an NMDA antagonist, MK-801 (0.5 mg/kg), in the same mGluR5 KO and WT mice. Results Between-group comparisons showed no significant differences in [ 18 F]FDG standardized uptake values (SUVs) in brain of mGluR5 KO and WT mice at baseline, but widespread reductions in mGluR5 KO mice compared to WT mice after MK-801 administration ( p   〈  0.05). The baseline glutamate levels did not differ significantly between the two groups. However, there were significant negative correlations between baseline prefrontal glutamate levels and regional [ 18 F]FDG SUVs in mGluR5 KO mice ( p   〈  0.05), but no such correlations in WT mice. Fisher’s Z-transformation analysis revealed significant between-group differences in these correlations ( p   〈  0.05). Conclusions This is the first multimodal neuroimaging study in mGluR5 KO mice and the first report on the association between cerebral glucose metabolism and glutamate levels in living rodents. The results indicate that mGluR5 KO mice respond to NMDA antagonism with reduced cerebral glucose metabolism, suggesting that mGluR5 transmission normally moderates the net effects of NMDA receptor antagonism on neuronal activity. The negative correlation between glutamate levels and glucose metabolism in mGluR5 KO mice at baseline may suggest an unmasking of an inhibitory component of the glutamatergic regulation of neuronal energy metabolism.
    Type of Medium: Online Resource
    ISSN: 2191-219X
    URL: Article
    DOI: 10.1186/s13550-020-00716-z
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2619892-7
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  • 3
    Online Resource
    Online Resource
    Relationship of self‐transcendence traits with in vivo dopamine D2/3 receptor availability and functional connectivity: An [ 18 F]fallypride PET and fMRI study
    Wiley ; 2019
    In:  Synapse Vol. 73, No. 11 ( 2019-11)
    Details
    In: Synapse, Wiley, Vol. 73, No. 11 ( 2019-11)
    Abstract: Genetic research has implicated dopamine neurotransmission in the expression of the self‐transcendence trait in humans. However, molecular imaging of dopaminergic markers is undocumented in relation to this personality trait. In this multimodal imaging study, we first investigated the relationship between the self‐transcendence trait and in vivo dopamine D 2/3 receptor availability using [ 18 F]fallypride positron emission tomography (PET). We next conducted seed‐based functional connectivity analyses using resting‐state functional magnetic resonance imaging (rs‐fMRI) data with regions derived from the PET analysis as seeds to explore the functional significance of D 2/3 receptor availability foci associated with the self‐transcendence trait. Twenty‐one healthy subjects underwent high‐resolution PET with [ 18 F]fallypride and a subset of 18 subjects also completed 3‐Tesla rs‐fMRI. The Temperament and Character Inventory was used to measure the self‐transcendence trait. A voxel‐based whole brain analysis revealed that the [ 18 F]fallypride binding potential (BP ND ) within the cluster of the left insula was significantly positively correlated with self‐transcendence trait scores. A region‐of‐interest analysis also showed a significant positive correlation between self‐transcendence and [ 18 F]fallypride BP ND in the left insula. The exploratory [ 18 F]fallypride BP ND seed‐based rs‐fMRI analysis showed that the functional connectivity from the left insula seed to the prefrontal cortices (including the inferior frontal region) was negatively associated with self‐transcendence trait scores. The results of the present study suggest that D 2/3 receptor‐mediated neurotransmission in the left insula may constitute a significant neurobiological factor in the self‐transcendence trait. The negative associations between BP ND seed‐based functional connectivity and self‐transcendence trait scores may suggest reduced prefrontal control in this personality trait.
    Type of Medium: Online Resource
    ISSN: 0887-4476 , 1098-2396
    URL: Issue
    URL: Article
    DOI: 10.1002/syn.v73.11
    DOI: 10.1002/syn.22121
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 1474927-0
    SSG: 12
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  • 4
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    Online Resource
    Functional Analysis of Brain Imaging Suggests Changes in the Availability of mGluR5 and Altered Connectivity in the Cerebral Cortex of Long-Term Abstaining Males with Alcohol Dependence: A Preliminary Study
    MDPI AG ; 2021
    In:  Life Vol. 11, No. 6 ( 2021-05-30), p. 506-
    Details
    In: Life, MDPI AG, Vol. 11, No. 6 ( 2021-05-30), p. 506-
    Abstract: Direct in vivo evidence of altered metabotropic glutamate receptor-5 (mGluR5) availability in alcohol-related disorders is lacking. We performed [11C]ABP688 positron emission tomography (PET) and resting-state functional magnetic resonance imaging (rs-fMRI) in prolonged abstinent subjects with alcohol dependence to examine alterations of mGluR5 availability, and to investigate their functional significance relating to neural systems-level changes. Twelve prolonged abstinent male subjects with alcohol dependence (median abstinence duration: six months) and ten healthy male controls underwent [11C] ABP688 PET imaging and 3-Tesla MRI. For mGluR5 availability, binding potential (BPND) was calculated using the simplified reference tissue model with cerebellar gray matter as the reference region. The initial region-of-interest (ROI)-based analysis yielded no significant group differences in mGluR5 availability. The voxel-based analysis revealed significantly lower [11C]ABP688 BPND in the middle temporal and inferior parietal cortices, and higher BPND in the superior temporal cortex in the alcohol dependence group compared with controls. Functional connectivity analysis of the rs-fMRI data employed seed regions identified from the quantitative [11C] ABP688 PET analysis, which revealed significantly altered functional connectivity from the inferior parietal cortex seed to the occipital pole and dorsal visual cortex in the alcohol dependence group compared with the control group. To our knowledge, this is the first report on the combined analysis of mGluR5 PET imaging and rs-fMRI in subjects with alcohol dependence. These preliminary results suggest the possibility of region-specific alterations of mGluR5 availability in vivo and related functional connectivity perturbations in prolonged abstinent subjects.
    Type of Medium: Online Resource
    ISSN: 2075-1729
    URL: Article
    DOI: 10.3390/life11060506
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662250-6
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  • 5
    Online Resource
    Online Resource
    Altered connectivity between striatal and extrastriatal regions in patients with schizophrenia on maintenance antipsychotics: an [ 18 F]fallypride PET and functional MRI study
    Wiley ; 2018
    In:  Synapse Vol. 72, No. 12 ( 2018-12)
    Details
    In: Synapse, Wiley, Vol. 72, No. 12 ( 2018-12)
    Abstract: In addition to probing regional differences in receptor availability, molecular positron emission tomography (PET) is proving useful for investigating perturbations in neurotransmitter networks using interregional correlation analyses. In a multi‐modal imaging study, we examined interregional correlations of dopamine D 2/3 receptor availability between striatal and extrastriatal regions using [ 18 F]fallypride high‐resolution PET in 11 patients with schizophrenia receiving low‐dose maintenance atypical antipsychotics and 14 healthy control subjects, and investigated resting‐state functional connectivity in the same subjects using seed‐based functional magnetic resonance imaging (fMRI) analysis. In the healthy control group, there were no significant correlations of [ 18 F]fallypride binding potential (BP ND ) between striatal regions and any cortical areas, whereas the patient group showed significant and widespread inter‐correlations. Correlations between BP ND in striatum, amygdala and insula with cortex were significantly higher in patients than in controls. In seed‐based resting‐state fMRI analysis, the healthy controls revealed positive and negative functional connectivity patterns, while patients exhibited a pattern of exclusively positive connectivity. Functional connectivity was significantly higher between striatal regions and extrastriatal areas including cortical regions in patients compared to controls. In this first such report, molecular and functional connectivity between striatal and extrastriatal regions was primarily characterized by increased interregional relationships in treated patients with schizophrenia. The results suggest that the spatial organization of D 2/3 receptor availability and related functional connectivity are significantly perturbed in stable outpatients on maintenance antipsychotics. Future studies should include antipsychotic‐naïve patients to determine if these relationships are illness‐related characteristics, or arising due to chronic antipsychotic treatment.
    Type of Medium: Online Resource
    ISSN: 0887-4476 , 1098-2396
    URL: Issue
    URL: Article
    DOI: 10.1002/syn.2018.72.issue-12
    DOI: 10.1002/syn.22064
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 1474927-0
    SSG: 12
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