Striatum on the anxiety map: Small detours into adolescence

Lago, Tiffany R.; Davis, Andrew A.; Grillon, Christian; Ernst, Monique

doi:10.1016/j.brainres.2016.06.006

Cited by 115 publications

(84 citation statements)

References 126 publications

(179 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Besides the amygdala, striatum, hippocampus, hypothalamus and basal forebrain and septum had high fractions of 2-subunit containing diazepam-sensitive GABA A receptors in our PET study. All these regions are suggested to be involved in the neuronal network of anxiety (Lago et al, 2016). Besides the data from the region-of-interest analysis, the images of the voxel-wise mapping of 2-containing receptors are in good agreement with the suggested circuits of anxiety (Lago et al, 2016).…”

Section: Distribution Of 1 2 and 5-containing Diazepam-sensitivesupporting

confidence: 64%

GABAA receptor subtypes in the mouse brain: Regional mapping and diazepam receptor occupancy by in vivo [18F]flumazenil PET

et al. 2017

View full text Add to dashboard Cite

Classical benzodiazepines, which are widely used as sedatives, anxiolytics and anticonvulsants, exert their therapeutic effects through interactions with heteropentameric GABA receptors composed of two α, two β and one γ2 subunit. Their high affinity binding site is located at the interface between the γ2 and the adjacent α subunit. The α-subunit gene family consists of six members and receptors can be homomeric or mixed with respect to the α-subunits. Previous work has suggested that benzodiazepine binding site ligands with selectivity for individual GABA receptor subtypes, as defined by the benzodiazepine-binding α subunit, may have fewer side effects and may even be effective in diseases, such as schizophrenia, autism or chronic pain, that do not respond well to classical benzodiazepines. The distributions of the individual α subunits across the CNS have been extensively characterized. However, as GABA receptors may contain two different α subunits, the distribution of the subunits does not necessarily reflect the distribution of receptor subtypes with respect to benzodiazepine pharmacology. In the present study, we have used in vivo [F]flumazenil PET and in vitro [H]flumazenil autoradiography in combination with GABA receptor point-mutated mice to characterize the distribution of the two most prevalent GABA receptor subtypes (α1 and α2) throughout the mouse brain. The results were in agreement with published in vitro data. High levels of α2-containing receptors were found in brain regions of the neuronal network of anxiety. The α1/α2 subunit combinations were predictable from the individual subunit levels. In additional experiments, we explored in vivo [F]flumazenil PET to determine the degree of receptor occupancy at GABA receptor subtypes following oral administration of diazepam. The dose to occupy 50% of sensitive receptors, independent of the receptor subtype(s), was 1-2mg/kg, in agreement with published data from ex vivo studies with wild type mice. In conclusion, we have resolved the quantitative distribution of α1- and α2-containing homomeric and mixed GABA receptors in vivo at the millimeter scale and demonstrate that the regional drug receptor occupancy in vivo at these GABA receptor subtypes can be determined by [F]flumazenil PET. Such information should be valuable for drug development programs aiming for subtype-selective benzodiazepine site ligands for new therapeutic indications.

show abstract

Section: Distribution Of 1 2 and 5-containing Diazepam-sensitivesupporting

confidence: 64%

GABAA receptor subtypes in the mouse brain: Regional mapping and diazepam receptor occupancy by in vivo [18F]flumazenil PET

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Such adaptations could include a shift of mitochondrial respiration towards (potentially protective) stronger reliance on succinate- / mitochondrial Complex ll-linked respiration (S f ), which is blocked by chronic CORT. Interestingly, the effect size of S E FCR between PFF(C) and PFF groups is comparable to the differences observed in anxiety-like behaviors, behaviors with important striatal participation 66 .…”

Section: Discussionsupporting

confidence: 65%

Chronic corticosterone enhancement aggravates alpha-synuclein brain spreading pathology and substantia nigra neurodegeneration in mice

Burtscher

Copin

Rodrigues

et al. 2018

Preprint

View full text Add to dashboard Cite

Chronic stress and associated heightened glucocorticoid levels are risk factors for depression, a common non-motor symptom in Parkinson’s disease (PD). However, how heightened glucocorticoids influence PD neuropathology [alpha-synuclein (α-Syn) containing Lewy pathology and neurodegeneration] and disease progression is unclear. To address this knowledge gap, we investigated the impact of chronic corticosterone administration on α-Syn pathology, neurodegeneration, behavior and mitochondrial function in a mouse model of α-Syn pathology spreading after intracerebral injection of α-Syn preformed fibrils (PFFs). Our results demonstrate that heightened corticosterone aggravates neurodegeneration and α-Syn pathology spreading, intriguingly to specific brain regions, such as the entorhinal cortex. Corticosterone-treatment abolished distinct physiological adaptations after PFF-injection and induced differential physiological and behavioral consequences. Taken together, our work points to elevated glucocorticoids as a risk factor for the development of the neuropathological hallmarks of PD. Strategies aimed at reducing glucocorticoid levels might slow down pathology spreading and disease progression in synucleinopathy.

show abstract

“…It has been shown that, compared with HC, patients with SAD lack a processing advantage in the putamen for social rewards relative to social punishments ( 92 ). Hence, these findings provided further evidence that structural alterations in the putamen might play a role in the pathophysiology underlying the imbalance in approach-avoidance motivation in SAD [see also ( 93 )].…”

Section: Discussionmentioning

confidence: 68%

Gray Matter Structural Alterations in Social Anxiety Disorder: A Voxel-Based Meta-Analysis

et al. 2018

View full text Add to dashboard Cite

The current insight into the neurobiological pathogenesis underlying social anxiety disorder (SAD) is still rather limited. We implemented a meta-analysis to explore the neuroanatomical basis of SAD. We undertook a systematic search of studies comparing gray matter volume (GMV) differences between SAD patients and healthy controls (HC) using a whole-brain voxel-based morphometry (VBM) approach. The anisotropic effect size version of seed-based d mapping (AES-SDM) meta-analysis was conducted to explore the GMV differences of SAD patients compared with HC. We included eleven studies with 470 SAD patients and 522 HC in the current meta-analysis. In the main meta-analysis, relative to HC, SAD patients showed larger GMVs in the left precuneus, right middle occipital gyrus (MOG) and supplementary motor area (SMA), as well as smaller GMV in the left putamen. In the subgroup analyses, compared with controls, adult patients (age ≥ 18 years) with SAD exhibited larger GMVs in the left precuneus, right superior frontal gyrus (SFG), angular gyrus, middle temporal gyrus (MTG), MOG and SMA, as well as a smaller GMV in the left thalamus; SAD patients without comorbid depressive disorder exhibited larger GMVs in the left superior parietal gyrus and precuneus, right inferior temporal gyrus, fusiform gyrus, MTG and superior temporal gyrus (STG), as well as a smaller GMV in the bilateral thalami; and currently drug-free patients with SAD exhibited a smaller GMV in the left thalamus compared with HC while no larger GMVs were found. For SAD patients with different clinical features, our study revealed directionally consistent larger cortical GMVs and smaller subcortical GMVs, including locationally consistent larger precuneus and thalamic deficits in the left brain. Age, comorbid depressive disorder and concomitant medication use of the patients might be potential confounders of SAD at the neuroanatomical level.

show abstract

Striatum on the anxiety map: Small detours into adolescence

Cited by 115 publications

References 126 publications

GABAA receptor subtypes in the mouse brain: Regional mapping and diazepam receptor occupancy by in vivo [18F]flumazenil PET

GABAA receptor subtypes in the mouse brain: Regional mapping and diazepam receptor occupancy by in vivo [18F]flumazenil PET

Chronic corticosterone enhancement aggravates alpha-synuclein brain spreading pathology and substantia nigra neurodegeneration in mice

Gray Matter Structural Alterations in Social Anxiety Disorder: A Voxel-Based Meta-Analysis

Contact Info

Product

Resources

About