Previous strength training attenuates ouabain-induced bipolar disorder-related behaviors and memory deficits in rats: Involvement of hippocampal ERK/CREB and PI3K/AKT/mTOR pathways

Article

Author: Godinho, Douglas Buchmann ; Guerra, Jozyê Milena da Silva ; Rambo, Leonardo Magno ; Royes, Luis Fernando Freire ; Paiva, Eduarda Goulart ; Souza-Pereira, Adson ; Maidana, Luan Machado ; Moreira-Silva, Mayckel Jean ; Lins, Marizabel Parente

Bipolar disorder (BD) is a central nervous system condition that is typified by fluctuations in mood, oscillating between depressive and manic, and/or hypomanic episodes. The objective of this study was to test the hypothesis that strength training may act as a potent protector against behavioral and neurochemical changes induced by BD. A strength training protocol was performed with adult male Wistar rats, and seven days following the conclusion of training, a single ouabain injection was administered. Following ouabain administration, the animals were subjected to behavioral tests after the seventh (manic period) and fourteenth (depressive period) days. Subsequently, rats were euthanized and the hippocampus was collected for western blotting assays. We demonstrated that strength training provided protection against ouabain-induced behavioral changes, both during the manic and depressive periods, including increased locomotor activity, risk-taking and aggressive-like behaviors, and impaired memory performance. Furthermore, physical training protected against ouabain-induced decrease of neurogenesis/neuroplasticity-related pathways, including BDNF/TrKB/ERK/CREB and PI3K/AKT/mTOR/p70S6K. These findings suggest that strength training has a protective effect, attenuating or preventing BD-induced deficits, and may have therapeutic potential as an adjuvant treatment for this patient population in the future.

01 Jan 2025·Experimental Cell Research

The cystogenic effects of ouabain in autosomal dominant polycystic kidney disease require cell caveolae

Article

Author: McDermott, Jeffery P ; Sanchez, Gladis ; Blanco, Gustavo ; McDermott, Jeffery P. ; Trant, Jordan

We have previously shown that the hormone ouabain is a circulating factor which can accelerate the progression of autosomal dominant polycystic kidney disease (ADPKD). At physiologic concentrations, ouabain increases cyst area and fibrosis in kidneys from ADPKD but not wildtype mice. These effects are due to an increased affinity for ouabain by its receptor, Na,K-ATPase (NKA), in the kidneys of ADPKD mice which leads to over-activation of NKA signaling function. Previous studies suggested that ouabain's stimulation of NKA signal transduction is mediated by NKA located within cell caveolae. Here, we determined whether caveolae are involved in the ouabain-induced progression of ADPKD cysts. We generated an ADPKD mouse with a global knockout of the main structural component of caveolae, caveolin-1 (CAV1), which we confirmed lacks caveolae in the kidney. When given physiological amounts of ouabain for 5 months, Pkd1^RC/RCCav1^-/- mice did not exhibit any changes in cyst progression, contrasting with the Pkd1^RC/RC mice which showed a significant increase in cystic area and kidney fibrosis. Also, measures of ouabain-induced cell proliferation, including the number of Ki67-positive nuclei and phosphorylation of the extracellular regulated kinase (ERK) and protein kinase B (Akt), did not increase in the Pkd1^RC/RCCav1^-/- mice compared with the Pkd1^RC/RC mice. Moreover, the abnormally increased affinity for ouabain of NKA in Pkd1^RC/RC mice was restored to wildtype levels in the Pkd1^RC/RCCav1^-/- mice. This work highlights the role of caveolae in ouabain-induced NKA signaling and ADPKD cyst progression.

01 Jan 2025·Journal of Neurophysiology

Recovery from spreading depolarization is slowed by aging and accelerated by antioxidant treatment in locusts

Article

Author: Wang, Yuyang ; Robertson, R. Meldrum

Anoxia and similar energetic crises trigger a shutdown of central neural processing in a process of spreading depolarization (SD) that is generally pathological in mammals and protective in insects. We show that older animals are slower to recover from SD in an insect model. Moreover, preventing oxidative stress with an antioxidant speeds recovery. These findings demonstrate the role of oxidative stress in contributing to the vulnerability of the aging insect central nervous system (CNS) in energetic emergencies.

100 Deals associated with Ouabain

External Link

KEGG	Wiki	ATC	Drug Bank
D00112	Ouabain	C01AC01	DB01092

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Heart Failure	-	-	-

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASN2018	Not Applicable	Renal Cell Carcinoma	-	Ouabain	qkhyzeyioa(pcnhtutayr) = klhjnhhkki dnnqymdgsp (fymysmkvhe )	-	23 Oct 2018
ASN2016	Not Applicable	Diabetic Nephropathies	-	Ouabain (Glucose 10mM)	xeuaanxjat(partslmrha) = juqtqpabxa cojiitypfv (kruaygvxeb, 4.1)	Positive	15 Nov 2016
				Ouabain 5nM	xeuaanxjat(partslmrha) = nsqczidokh cojiitypfv (kruaygvxeb, 1.3)
ASN2014	Not Applicable	Hypertension serum uric acid \| endogenous ouabain \| ATP-binding cassette B1 gene	222	Ouabain (ABCB1 rs1045642 genotype)	opyyihufnk(phfuzqtfrg) = hpgxyizfnu dvrywhbxsa (rsyzeautkv )	-	11 Nov 2014
ASN2014	Not Applicable	Proteinuria ouabain	-	Rostafuroxin 100 µg/kg/day	(dkyosbucoy) = kmofnrknep wtzlslbski (xgqrmlktbi ) View more	Positive	11 Nov 2014
				Ouabain	(dkyosbucoy) = ybxhqsswzo wtzlslbski (xgqrmlktbi ) View more
ASN2012	Not Applicable	Dysentery, Bacillary Stx2 \| Gb3 receptors \| Bax ... View more	-	Ouabain/Na,K-ATPase (Stx2)	llhweejfds(zvefsuiyvt) = uouctcappi uhdyesvqae (aueleqgrsv ) View more	Positive	30 Oct 2012
				Ouabain	llhweejfds(zvefsuiyvt) = ehexdhmefq uhdyesvqae (aueleqgrsv ) View more
ASN2010	Not Applicable	Hypertension Na-K ATPase \| NHE-1	-	Ouabain	(eiytukpaxo) = fxcuapaufg qswslpbonk (qeaudsmdes, 3.26)	Positive	16 Nov 2010
				Vehicle	(eiytukpaxo) = yfbksijqpi qswslpbonk (qeaudsmdes, 5.32)
ARVO2008	Not Applicable	-	-	Ouabain 30 nM	oxfkkrvhlb(warrznaypa) = deluaoifik akvzjudpuu (zsmsdpicsj )	-	01 May 2008
				Ouabain (Control)	oxfkkrvhlb(warrznaypa) = mmwbzumqzp akvzjudpuu (zsmsdpicsj )
SFN2007	Not Applicable	Cerebellar Neoplasms	-	Ouabain	kifmblhchm(njejaoysui) = zhhkdpgzhf weztlubdpf (dswgludgxl, 1.7)	-	04 Nov 2007
ARVO2005	Not Applicable	Iris Pigment Epithelium Anomalies	-	Ouabain	hqkyugqdjj(yxvrupszcf) = ouabain did enhance BKCa-channel activity without a change in single-channel amplitude cjssjrubbg (cdysniialh )	-	01 May 2005

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