Role of klotho on antidepressant and antisuicidal effects of low-dose ketamine infusion among patients with treatment-resistant depression and suicidal ideation

Chen, Mu Hong; Bai, Ya‐Mei; Wu, Hui-Ju; Li, Cheng Ta; Lin, Wei‐Chen; Tsai, Shih‐Jen; Su, Tung‐Ping; Tu, Pei-Chi

doi:10.1016/j.jad.2023.08.061

Cited by 3 publications

(5 citation statements)

References 29 publications

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“…At the same time, no relationship was found between changes in Klotho concentration and changes in depressive and suicidal symptoms. On the other hand, higher baseline levels of Klotho were related to a weaker antidepressant effect of low-dose ketamine during the post-infusion follow-up [6]. These studies also support the association between Klotho and glutamatergic transmission, which has been previously suggested in animal studies [73,74].…”

Section: The Role Of Klotho In Antidepressant Therapysupporting

confidence: 86%

“…No relationship between changes in Klotho levels and changes in depressive and suicidal symptoms Higher baseline levels of Klotho were associated with a weaker antidepressant effect of low-dose ketamine during the post-infusion follow-up [6]…”

Section: ↑ Klotho Levels In Patients On Day 3 After Ketamine Infusionmentioning

confidence: 96%

“…It follows that the regulation of the Klotho protein by NMDA receptors may be a new strategy or molecular target for the pharmacological treatment of depression. Chen et al (2023) showed that the effect of low-dose ketamine may be associated with the regulation of serum Klotho levels in patients with TRD [6]. In contrast, in vitro studies conducted in cultures of mouse hippocampal neurons treated for 24 h with a mixture of AMPA and NMDA antagonists (NBQX, APV-20 µM, respectively) showed that the Klotho content in neurons was significantly lower than that in vehicle-treated cells [146].…”

Section: Klotho and Glutamate-the Possible Role Of Klotho In Neurotra...mentioning

confidence: 99%

“…Recently approved by the FDA (2019), ketamine (N-methyl-D-aspartate (NMDA) receptor antagonist with additional effects on α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, Ltype voltage-dependent calcium channel (L-VDCC), hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, opioid receptors, and monoaminergic receptors) is an essential drug for the treatment of drug-resistant and suicidal depression, but its use is associated with many side effects [2][3][4][5]. Nevertheless, the success of ketamine as a fast-acting antidepressant has been an important impetus for extensive research into new antidepressants, the mechanisms of action of antidepressants (especially regarding their role in synaptic targets), and the pathomechanisms of depression [2,3,6].…”

Section: Introductionmentioning

confidence: 99%

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The Importance of α-Klotho in Depression and Cognitive Impairment and Its Connection to Glutamate Neurotransmission—An Up-to-Date Review

Pańczyszyn-Trzewik,

Czechowska,

Stachowicz

et al. 2023

IJMS

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Depression is a serious neuropsychiatric disease affecting an increasing number of people worldwide. Cognitive deficits (including inattention, poor memory, and decision-making difficulties) are common in the clinical picture of depression. Cognitive impairment has been hypothesized to be one of the most important components of major depressive disorder (MDD; referred to as clinical depression), although typical cognitive symptoms are less frequent in people with depression than in people with schizophrenia or bipolar disorder (BD; sometimes referred to as manic-depressive disorder). The importance of α-Klotho in the aging process has been well-documented. Growing evidence points to the role of α-Klotho in regulating other biological functions, including responses to oxidative stress and the modulation of synaptic plasticity. It has been proven that a Klotho deficit may contribute to the development of various nervous system pathologies, such as behavioral disorders or neurodegeneration. Given the growing evidence of the role of α-Klotho in depression and cognitive impairment, it is assumed that this protein may be a molecular link between them. Here, we provide a research review of the role of α-Klotho in depression and cognitive impairment. Furthermore, we propose potential mechanisms (related to oxidative stress and glutamatergic transmission) that may be important in α-Klotho-mediated regulation of mental and cognitive function.

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Section: The Role Of Klotho In Antidepressant Therapysupporting

confidence: 86%

Section: ↑ Klotho Levels In Patients On Day 3 After Ketamine Infusionmentioning

confidence: 96%

Section: Klotho and Glutamate-the Possible Role Of Klotho In Neurotra...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Importance of α-Klotho in Depression and Cognitive Impairment and Its Connection to Glutamate Neurotransmission—An Up-to-Date Review

Pańczyszyn-Trzewik,

Czechowska,

Stachowicz

et al. 2023

IJMS

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show abstract

“…Thus, it appears that the development of novel antidepressants is not an ideal strategy to address the problems in the treatment of depression. More importantly, although some drugs such as ketamine are more effective at low doses in relieving depressive symptoms in treatment-resistant patients than conventional clinically available antidepressants (Chen et al ., 2023a; Zaki et al ., 2023), most of the so-called newly developed drugs for the treatment of depression are not considered more effective than conventional antidepressants (Brown et al ., 2011; Richards et al ., 2017). In light of this, strategies can be developed to improve the therapeutic efficacy of conventional antidepressants by adding complementary or therapeutic alternatives to those that do not show excellent efficacy (Fava et al ., 2006).…”

Section: Discussionmentioning

confidence: 99%

NSC689857, an inhibitor of Skp2, produces antidepressant-like effects in mice

Liu,

Cheng,

et al. 2024

Behavioural Pharmacology

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We have previously reported that two inhibitors of an E3 ligase S-phase kinase-associated protein 2 (Skp2), SMIP004 and C1, have an antidepressant-like effect in non-stressed and chronically stressed mice. This prompted us to ask whether other Skp2 inhibitors could also have an antidepressant effect. Here, we used NSC689857, another Skp2 inhibitor, to investigate this hypothesis. The results showed that administration of NSC689857 (5 mg/kg) produced an antidepressant-like effect in a time-dependent manner in non-stressed male mice, which started 8 days after drug administration. Dose-dependent analysis showed that administration of 5 and 10 mg/kg, but not 1 mg/kg, of NSC689857 produced antidepressant-like effects in both non-stressed male and female mice. Administration of NSC689857 (5 mg/kg) also induced antidepressant-like effects in non-stressed male mice when administered three times within 24 h (24, 5, and 1 h before testing) but not when administered acutely (1 h before testing). In addition, NSC689857 and fluoxetine coadministration produced additive antidepressant-like effects in non-stressed male mice. These effects of NSC689857 were not associated with the changes in locomotor activity. Administration of NSC689857 (5 mg/kg) also attenuated depression-like behaviors in male mice induced by chronic social defeat stress, suggesting therapeutic potential of NSC689857 in depression. Overall, these results suggest that NSC689857 is capable of exerting antidepressant-like effects in both non-stressed and chronically stressed mice.

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Association between serum Klotho and major depression: Results from the NHANES 2007–2016 and Mendelian randomization studies

Zhang,

Guan,

et al. 2024

Journal of Affective Disorders

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Role of klotho on antidepressant and antisuicidal effects of low-dose ketamine infusion among patients with treatment-resistant depression and suicidal ideation

Cited by 3 publications

References 29 publications

The Importance of α-Klotho in Depression and Cognitive Impairment and Its Connection to Glutamate Neurotransmission—An Up-to-Date Review

The Importance of α-Klotho in Depression and Cognitive Impairment and Its Connection to Glutamate Neurotransmission—An Up-to-Date Review

NSC689857, an inhibitor of Skp2, produces antidepressant-like effects in mice

Association between serum Klotho and major depression: Results from the NHANES 2007–2016 and Mendelian randomization studies

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