Dose-dependent effect of AdipoRon on modulating adult hippocampal neurogenesis and neurocognitive behaviours in mice

Lee, Ho Yin Thomas; Ahadullah,; Yau, Sonata Suk Yu

doi:10.1016/j.ibror.2019.07.1231

Cited by 3 publications

(9 citation statements)

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“…Such therapeutic approaches would work only when the obligatory co-receptor T-cadherin is still present. In contrast, insulin resistance plus hyperadiponectinemia (and absence of membrane-bound T-cadherin) would require AdipoR agonists such as AdipoRon [79][80][81] that act independently of the co-receptor T-cadherin, or alternatively compounds such metformin (see below) that directly activate the intracellular signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

An Explanation for the Adiponectin Paradox

Kalkman¹

2021

Pharmaceuticals

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The adipokine adiponectin improves insulin sensitivity. Functional signal transduction of adiponectin requires at least one of the receptors AdipoR1 or AdipoR2, but additionally the glycosyl phosphatidylinositol-anchored molecule, T-cadherin. Overnutrition causes a reduction in adiponectin synthesis and an increase in the circulating levels of the enzyme glycosyl phosphatidylinositol-phospholipase D (GPI-PLD). GPI-PLD promotes the hydrolysis of T-cadherin. The functional consequence of T-cadherin hydrolysis is a reduction in adiponectin sequestration by responsive tissues, an augmentation of adiponectin levels in circulation and a (further) reduction in signal transduction. This process creates the paradoxical situation that adiponectin levels are augmented, whereas the adiponectin signal transduction and insulin sensitivity remain strongly impaired. Although both hypoadiponectinemia and hyperadiponectinemia reflect a situation of insulin resistance, the treatments are likely to be different.

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Section: Discussionmentioning

confidence: 99%

An Explanation for the Adiponectin Paradox

Kalkman¹

2021

Pharmaceuticals

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“…We have previously shown that adiponectin signaling is a key mediator of the neurogenic and antidepressant properties of voluntary wheel running [12,24]. Moreover, our group has also shown that chronic treatment with AdipoRon, a synthetic and orally available adiponectin receptor agonist [17], increases hippocampal neurogenesis in a dose-dependent manner [25] and mimics the effects of physical exercise on restoring hippocampal neuroplasticity and cognitive deficits in diabetic mice [26].…”

Section: Introductionmentioning

confidence: 91%

“…AdipoRon (MedChemExpress, Princeton, NJ, USA) was dissolved in 0.5% carboxymethylcellulose sodium salt (CMC) (Sigma-Aldrich, St. Loius, MO, USA) at 70 • C in 5% DMSO, as previously performed (26). Animals were treated with AdipoRon (20 mg/kg, i.p.)…”

Section: Drugsmentioning

confidence: 99%

“…Brain slices were prepared as previously described [26]. Brains were isolated from adult male mice (8-9 weeks old) 22 to 24 h after the last AdipoRon injection and immersed in a chilled artificial cerebrospinal fluid (ACSF) containing (in mM) 125 NaCl, 25 NaHCO 3 , 3 KCl, 1.25 NaH 2 PO 4 , 10 D-glucose, 1 CaC l2 , and 6 MgCl 2 , and saturated with 95% O 2 /5% CO 2 .…”

Section: Tissue Preparation For Electrophysiologymentioning

confidence: 99%

“…The N-methyl-D-aspartate (NMDA) receptors play a significant role in hippocampal information processing [32][33][34], and NMDA receptor-associated structural and functional changes in the ventral hippocampal plasticity have been associated with mood impairments [35,36]. Although previous work has linked adiponectin's therapeutic effects with increased hippocampal neuroplasticity [12,13,[24][25][26], new evidence suggests that short-term antidepressant response might not rely on the hippocampus [37][38][39]. Inactivating the ventral hippocampus does not affect the ketamine's rapid antidepressant properties [37].…”

Section: Introductionmentioning

confidence: 99%

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Increasing Adiponectin Signaling by Sub-Chronic AdipoRon Treatment Elicits Antidepressant- and Anxiolytic-Like Effects Independent of Changes in Hippocampal Plasticity

Formolo

Lee

et al. 2023

Biomedicines

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(1) Background: Adiponectin is an adipocyte-secreted hormone that has antidepressant- and anxiolytic-like effects in preclinical studies. Here, we investigated the antidepressant- and anxiolytic-like effects of sub-chronic treatment with AdipoRon, an adiponectin receptor agonist, and its potential linkage to changes in hippocampal adult neurogenesis and synaptic plasticity. (2) Methods: Different cohorts of wild-type C57BL/6J and CamKIIα-Cre male mice were treated with sub-chronic (7 days) AdipoRon, followed by behavioral, molecular, and electrophysiological experiments. (3) Results: 7-day AdipoRon treatment elicited antidepressant- and anxiolytic-like effects but did not affect hippocampal neurogenesis. AdipoRon treatment reduced hippocampal brain-derived neurotrophic factor (BDNF) levels, neuronal activation in the ventral dentate gyrus, and long-term potentiation of the perforant path. The knockdown of N-methyl-D-aspartate (NMDA) receptor subunits GluN2A and GluN2B in the ventral hippocampus did not affect the antidepressant- and anxiolytic-like effects of AdipoRon. (4) Conclusions: Increasing adiponectin signaling through sub-chronic AdipoRon treatment results in antidepressant- and anxiolytic-like effects independent of changes in hippocampal structural and synaptic function.

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Adiponectin Attenuates Splenectomy-Induced Cognitive Deficits by Neuroinflammation and Oxidative Stress via TLR4/MyD88/NF-κb Signaling Pathway in Aged Rats

Zhang

Guo

Yang

et al. 2023

ACS Chem. Neurosci.

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Perioperative neurocognitive disorder (PND) is a common adverse event after surgical trauma in elderly patients. The pathogenesis of PND is still unclear. Adiponectin (APN) is a plasma protein secreted by adipose tissue. We have reported that a decreased APN expression is associated with PND patients. APN may be a promising therapeutic agent for PND. However, the neuroprotective mechanism of APN in PND is still unclear. In this study, 18 month old male Sprague-Dawley rats were assigned to six groups: the sham, sham + APN (intragastric (i.g.) administration of 10 μg/kg/day for 20 days before splenectomy), PND (splenectomy), PND + APN, PND + TAK-242 (intraperitoneal (i.p.) administration of 3 mg/kg TAK-242), and PND + APN + lipopolysaccharide (LPS) (i.p. administration of 2 mg/kg LPS). We first found that APN gastric infusion significantly improved learning and cognitive function in the Morris water maze (MWM) test after surgical trauma. Further experiments indicated that APN could inhibit the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor kappa B (NF-κb) p65 pathway to decrease the degree of oxidative damage (malondialdehyde (MDA) and superoxide dismutase (SOD)), microgliamediated neuroinflammation (ionized calcium binding adapter molecule 1 (IBA1), caspase-1, tumor necrosis factor (TNF)-α, interleukin-1β (IL-1β), and interleukin-6 (IL-6)), and apoptosis (p53, Bcl2, Bax, and caspase 3) in hippocampus. By using LPSspecific agonist and TAK-242-specific inhibitor, the involvement of TLR4 engagement was confirmed. APN intragastric administration exerts a neuroprotective effect against cognitive deficits induced by peripheral trauma, and the possible mechanisms include the inhibition of neuroinflammation, oxidative stress, and apoptosis, mediated by the suppression of the TLR4/MyD88/NFκb signaling pathway. We propose that oral APN may be a promising candidate for PND treatment.

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Dose-dependent effect of AdipoRon on modulating adult hippocampal neurogenesis and neurocognitive behaviours in mice

Cited by 3 publications

References 0 publications

An Explanation for the Adiponectin Paradox

An Explanation for the Adiponectin Paradox

Increasing Adiponectin Signaling by Sub-Chronic AdipoRon Treatment Elicits Antidepressant- and Anxiolytic-Like Effects Independent of Changes in Hippocampal Plasticity

Adiponectin Attenuates Splenectomy-Induced Cognitive Deficits by Neuroinflammation and Oxidative Stress via TLR4/MyD88/NF-κb Signaling Pathway in Aged Rats

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