Rapid antidepressant effect of ketamine correlates with astroglial plasticity in the hippocampus

Ardalan, Maryam; Rafati, Ali; Nyengaard, Jens Randel; Wegener, Gregers

doi:10.1111/bph.13714

Cited by 71 publications

(47 citation statements)

References 62 publications

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“…The present findings were in line with those of a clinical study in which increased hippocampal volumes were observed in patients who achieved remission following an infusion of ketamine, yet the study reported that the increased volumes were localized to the left side 18 . Animal studies also found that a single ketamine injection could induce increased volumes of the hippocampal CA1 and GCL regions twenty-four hours after the treatment in FSL rats 16 , and reverse the reduction of the number of granule cells in FSL-treated rats 30 . These findings support that rapid hippocampal structural plasticity induced by ketamine may be a potential mechanism underlying its fast antidepressant action.…”

Section: Discussionmentioning

confidence: 92%

Volumetric changes in subcortical structures following repeated ketamine treatment in patients with major depressive disorder: a longitudinal analysis

Zhou

Liu

et al. 2020

Transl Psychiatry

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Abnormal subcortical structures have been associated with major depressive disorder (MDD) and could be reversed by antidepressant treatment. To date no study has examined the relationship between subcortical volumes and repeated ketamine treatment. The current study investigated volume changes in specific subcortical structures and hippocampal subfields after six ketamine infusions. Forty-four patients with MDD received six subanesthetic dose infusions of ketamine. Depressive symptoms were assessed and magnetic resonance imaging scans were performed before and after six ketamine infusions. FreeSurfer software was used to process the T1 images and analyze the volumes of the subcortical regions and hippocampal subfields. After six ketamine infusions, increases were observed in the volumes of the left amygdala; the right hippocampus; the cornu ammonis 4 body, granule cell and molecular layer of the dentate gyrus body in the left hippocampus; and the cornu ammonis 4 head and molecular layer head in the right hippocampus. Positive correlations were found between symptom improvement and the pretreatment volumes of the right thalamus (r = 0.501; P = 0.001) and left subiculum head of the hippocampus (r = 0.471; P = 0.002), and changes in the volumes of the left amygdala (r = −0.452; P = 0.003) and the left cornu ammonis 4 body (r = −0.537; P < 0.001). Our findings provided evidence for critical roles of the amygdala and specific hippocampal subfields in the antidepressant effect of repeated ketamine treatment. Relatively larger volumes in right thalamus and left subiculum head in the hippocampus can predict a superior clinical outcome of ketamine treatment in MDD patients.

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Section: Discussionmentioning

confidence: 92%

Volumetric changes in subcortical structures following repeated ketamine treatment in patients with major depressive disorder: a longitudinal analysis

Zhou

Liu

et al. 2020

Transl Psychiatry

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“…Stereological analysis has shown that the volume of glial fibrillary acidic protein positive astrocytes is significantly lower in the hippocampus of Flinders Sensitive Line rats, which spontaneously develop a depression‐like phenotype (Ardalan et al . ). In this study, labeling in glutamate‐C4 (−27%) and glutamine‐C4 (−25%) from [2‐ 13 C]acetate in PFC of SD mice was reduced as compared with controls.…”

Section: Discussionmentioning

confidence: 97%

Subanesthetic ketamine reverses neuronal and astroglial metabolic activity deficits in a social defeat model of depression

Mishra

Kumar

Behar

et al. 2018

Journal of Neurochemistry

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Depression is one of the most debilitating neuropsychiatric disorders. Most of the current antidepressants have long remission time and low recovery rate. This study explores the impact of ketamine on neuronal and astroglial metabolic activity in prefrontal cortex in a social defeat (SD) model of depression. C57BL/6 mice were subjected to a social defeat paradigm for 5 min a day for 10 consecutive days. Ketamine (10 mg/kg, intraperitoneal) was administered to mice for two consecutive days following the last defeat stress. Mice were infused with [1,6- C ]glucose or [2- C]acetate to assess neuronal and astroglial metabolic activity, respectively, together with proton-observed carbon-edited nuclear magnetic resonance spectroscopy in prefrontal cortex tissue extract. The C labeling of amino acids from glucose and acetate was decreased in SD mice. Ketamine treatment in SD mice restored sucrose preference, social interaction and immobility time to control values. Acute subanesthetic ketamine restored the C labeling of brain amino acids from glucose as well as acetate in SD mice to the respective control values, suggesting that rates of neuronal and astroglial tricarboxylic acid (TCA) cycle and neurotransmitter cycling were re-established to normal levels. The finding of improved energy metabolism in SD mice suggests that fast anti-depressant action of ketamine is linked with improved neurotransmitter cycling.

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“…In the present study, we observed a positive correlation between changes in the astrocyte morphology including the lower number of astrocyte branches and hippocampal volume loss 4 days following SAH. It has been suggested that conditions which involve glial remodeling are associated with changes in the hippocampus volume ( Czeh and Lucassen, 2007 ), and a recent publication of our group indicated that changes in the volume of the hippocampus are correlated with the morphological alteration of astrocytes ( Ardalan et al, 2017 ). Therefore, we proposed that the observed hippocampal shrinkage in the SAH animals might reflect microstructural changes including astrocytes.…”

Section: Discussionmentioning

confidence: 99%

Hippocampal Atrophy Following Subarachnoid Hemorrhage Correlates with Disruption of Astrocyte Morphology and Capillary Coverage by AQP4

Anzabi

Ardalan

Iversen

et al. 2018

Front. Cell. Neurosci.

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Despite successful management of ruptured intracranial aneurysm following subarachnoid hemorrhage (SAH), delayed cerebral ischemia (DCI) remains the main cause of high mortality and morbidity in patients who survive the initial bleeding. Astrocytes play a key role in neurovascular coupling. Therefore, changes in the neurovascular unit including astrocytes following SAH may contribute to the development of DCI and long-term complications. In this study, we characterized morphological changes in hippocampal astrocytes following experimental SAH, with special emphasis on glia-vascular cross-talk and hippocampal volume changes. Four days after induction of SAH or sham-operation in mice, their hippocampal volumes were determined by magnetic resonance imaging (MRI) and histological/stereological methods. Glial fibrillary acid protein (GFAP) immunostained hippocampal sections were examined by stereological techniques to detect differences in astrocyte morphology, and global spatial sampling method was used to quantify the length density of Aquaporin-4 (AQP4) positive capillaries. Our results indicated that hippocampal volume, as measured both by MRI and by histological approaches, was significantly lower in SAH animals than in the sham-operated group. Accordingly, in this animal model of SAH, hippocampal atrophy existed already at the time of DCI onset in humans. SAH induced retraction of GFAP positive astrocyte processes, accompanied by a significant reduction in the length density of AQP4 positive capillaries as well as narrowing of hippocampal capillaries. Meanwhile, astrocyte volume was higher in SAH mice compared with the sham-operated group. Morphological changes in hippocampal astrocytes seemingly disrupt glia-vascular interactions early after SAH and may contribute to hippocampal atrophy. We speculate that astrocytes and astrocyte-capillary interactions may provide targets for the development of therapies to improve the prognosis of SAH.

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Rapid antidepressant effect of ketamine correlates with astroglial plasticity in the hippocampus

Cited by 71 publications

References 62 publications

Volumetric changes in subcortical structures following repeated ketamine treatment in patients with major depressive disorder: a longitudinal analysis

Volumetric changes in subcortical structures following repeated ketamine treatment in patients with major depressive disorder: a longitudinal analysis

Subanesthetic ketamine reverses neuronal and astroglial metabolic activity deficits in a social defeat model of depression

Hippocampal Atrophy Following Subarachnoid Hemorrhage Correlates with Disruption of Astrocyte Morphology and Capillary Coverage by AQP4

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