Astroglial glutamate transporter 1 and glutamine synthetase of the nucleus accumbens are involved in the antidepressant-like effects of allopregnanolone in learned helplessness rats

Nangaku, Masahito; Yoshino, Keiichi; Oda, Yasunori; Kimura, Makoto; Kimura, Hiroshi; Hirose, Yuki; Shirayama, Yukihiko; Iyo, Masaomi

doi:10.1016/j.bbr.2020.113092

Cited by 4 publications

(4 citation statements)

References 21 publications

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“…It has been confirmed that deficiencies in glutamate transport function in astrocytes may be an important pathological factor leading to the occurrence or persistence of depressive symptoms (Aizawa et al., 2020; Tordera et al., 2011). Some experimental evidence has demonstrated that antidepressant drugs can affect the expression levels of glial‐specific glutamate (Nangaku et al., 2021; Pham et al., 2020; Song et al., 2010). Furthermore, drugs targeting glutamate neurotransmission are hot candidates for novel antidepressant drugs (Lener et al., 2017).…”

Section: Discussionmentioning

confidence: 99%

Positive effects of running exercise on astrocytes in the medial prefrontal cortex in an animal model of depression

Huang

Xiao

Tang

et al. 2022

J of Comparative Neurology

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Depression is one of the most common mental illnesses and seriously affects all aspects of life. Running exercise has been suggested to prevent or alleviate the occurrence and development of depression; however, the underlying mechanisms of these effects remain unclear. Independent studies have indicated that astrocytes play essential roles and that the medial prefrontal cortex (mPFC) is an important brain region involved in the pathology underlying depression. However, it is unknown whether running exercise achieves antidepressant effects by affecting the number of astrocytes and glutamate transport function in the mPFC. Here, animal models of depression were established using chronic unpredictable stress (CUS), and depression-like behavior was assessed by the sucrose preference test. After successfully establishing the depression model, experimental animals performed running exercise. Glial fibrillary acidic protein-positive (GFAP + ) cell number in the mPFC was precisely quantified using immunohistochemical and stereological methods, and the densities of bromodeoxyuridine-positive (BrdU + ) and BrdU + /GFAP + cells in the mPFC were measured using a semiquantitative immunofluorescence assay. Changes in glutamate transporter gene expression in mPFC astrocytes were detected by mRNA sequencing and qRT-PCR. We found that running exercise reversed CUS-induced decreases in sucrose preference, increased astrocyte number and the density of newborn astrocytes, and reversed decreases in gene expression levels of GFAP, S100b, and the glutamate transporters GLT-1 and GLAST in the mPFC of CUS animals. These results suggested that changes in astrocyte number and glutamate transporter function may be potential meditators of the effects of running exercise in the treatment of depression.

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Section: Discussionmentioning

confidence: 99%

Positive effects of running exercise on astrocytes in the medial prefrontal cortex in an animal model of depression

Huang

Xiao

Tang

et al. 2022

J of Comparative Neurology

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“…211 In addition, it has been observed that, in the nucleus accumbens of learned helplessness rats (ie, an experimental model of depression), the astroglial glutamate transporter-1 and glutamine synthetase system is normalised by ALLO treatment. 212 In this context, it is interesting to note that effective antidepressant treatment is able to increase the reduced levels of ALLO observed in depressed patients. 213 In agreement, in an experimental model, the antidepressant fluoxetine was able to increase ALLO levels.…”

Section: Effects Of Allo In Pathological Conditionsmentioning

confidence: 99%

“…By contrast, the anti‐depressive effect exerted by ALLO, at least in the forced swimming model, appears also to involve the stimulation of dopamine D2‐like receptors 211 . In addition, it has been observed that, in the nucleus accumbens of learned helplessness rats (ie, an experimental model of depression), the astroglial glutamate transporter‐1 and glutamine synthetase system is normalised by ALLO treatment 212 . In this context, it is interesting to note that effective antidepressant treatment is able to increase the reduced levels of ALLO observed in depressed patients 213 .…”

Section: Effects Of Allo Under Physiological and Pathological Conditionsmentioning

confidence: 99%

Allopregnanolone: An overview on its synthesis and effects

Diviccaro

Cioffi

Falvo

et al. 2021

J Neuroendocrinology

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Allopregnanolone, a 3α,5α‐progesterone metabolite, acts as a potent allosteric modulator of the γ‐aminobutyric acid type A receptor. In the present review, the synthesis of this neuroactive steroid occurring in the nervous system is discussed with respect to physiological and pathological conditions. In addition, its physiological and neuroprotective effects are also reported. Interestingly, the levels of this neuroactive steroid, as well as its effects, are sex‐dimorphic, suggesting a possible gender medicine based on this neuroactive steroid for neurological disorders. However, allopregnanolone presents low bioavailability and extensive hepatic metabolism, limiting its use as a drug. Therefore, synthetic analogues or a different therapeutic strategy able to increase allopregnanolone levels have been proposed to overcome any pharmacokinetic issues.

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“…Effects on both systems are largely mediated through the progesterone metabolite, allopregnanolone. To impact glutamatergic signaling, allopregnanolone regulates behavior through its effects on expression of GLT1 and glutamine synthetase in the NAc [ 52 ]. Both chronic intermittent ethanol (CIE) exposure [ 53 ] and acute stress [ 54 ] increase glutamate release in the NAc, which subsequently can promote heightened reward seeking.…”

Section: Discussionmentioning

confidence: 99%

Estrous cycle and hormone regulation of stress-induced reinstatement of reward seeking in female mice

Giacometti

Buck

Barker

2022

Addiction Neuroscience

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Astroglial glutamate transporter 1 and glutamine synthetase of the nucleus accumbens are involved in the antidepressant-like effects of allopregnanolone in learned helplessness rats

Cited by 4 publications

References 21 publications

Positive effects of running exercise on astrocytes in the medial prefrontal cortex in an animal model of depression

Positive effects of running exercise on astrocytes in the medial prefrontal cortex in an animal model of depression

Allopregnanolone: An overview on its synthesis and effects

Estrous cycle and hormone regulation of stress-induced reinstatement of reward seeking in female mice

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