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 ; Maidana, Luan Machado ; Souza-Pereira, Adson ; 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 Feb 2025·Journal of Chemical Ecology

Entomopathogenic Nematode Species Vary in Their Behavior and Virulence in Response to Cardiac Glycosides Within and Around Insect Hosts

Article

Author: Pena, Robert ; Christensen, Preston ; Goldy, Connor ; Achi, Perla ; Bavier, Lanie ; Iglesias, Victoria ; McCarthy, Cullen ; Agrawal, Anurag A ; Dillman, Adler R ; Groen, Simon C

AbstractPlants produce defensive toxins to deter herbivores. In response, some specialized herbivores evolved resistance and even the capacity to sequester toxins, affecting interactions at higher trophic levels. Here, we test the hypothesis that potential natural enemies of specialized herbivores are differentially affected by plant toxins depending on their level of adaptation to the plant-herbivore system. We focus on toxic cardiac glycosides (CGs) from milkweeds (Asclepias spp.), which inhibit animal Na+/K+-ATPases, and two CG-resistant insects, the large milkweed bug Oncopeltus fasciatus and a CRISPR-edited Drosophila melanogaster. Both have CG-resistant Na+/K+-ATPases through a set of key amino acid substitutions, which facilitate CG sequestration. We conducted infection experiments with entomopathogenic nematodes (Steinernema carpocapsae, S. feltiae, and S. hermaphroditum) as natural enemies on host insects containing mixtures of milkweed-derived CGs or purified CGs (ouabain, digoxin, and digitoxin) that vary in toxicity. The nematode S. carpocapsae is known to occur in soil near milkweed plants and naturally has several of the same Na+/K+-ATPase substitutions as the milkweed bug O. fasciatus and our Drosophila mutant. This nematode not only exhibited higher fecundity in hosts that carried CGs relative to the other nematode species (which have sensitive Na+/K+-ATPases), but also showed attraction to mixtures of CGs in milkweed root extracts and to purified ouabain when tested on agar plates. A coiling phenotype, which is a symptom of neurotoxicity, was observed more frequently in S. feltiae and S. hermaphroditum upon exposure to milkweed root extracts than in S. carpocapsae. Nematode behavior was further tested in sand, and while attraction to CGs was found for S. carpocapsae, nematodes of the other species tended to migrate away from milkweed root chemicals. Thus, S. carpocapsae can tolerate CGs and may use these as chemical cues to locate insect hosts that live on or around milkweed plants.

01 Feb 2025·Journal of Chemical Ecology

Regionality and Temporal Dynamics of Sequestration and Relocation of Cardenolides in the Monarch Butterfly, Danaus plexippus

Author: Betz, Anja ; Hoeglinger, Birgit ; Walker, Frank ; Petschenka, Georg

AbstractThe adaptation of monarch butterflies (Danaus plexippus) to milkweed plants and their ability to sequester toxic cardenolides is a model system for plant-herbivore coevolution. However, the physiological mechanisms underlying cardenolide sequestration and its temporal dynamics remain largely unknown. Here, we show that the polar cardenolide ouabain passes through the isolated midgut epithelium of D. plexippus in vitro and is also absorbed into the body cavity of monarch caterpillars. Remarkably, the same pattern was observed in caterpillars of the related, but non-sequestering milkweed butterfly Euploea core, and even in the non-adapted Solanaceae specialist Manduca sexta, although uptake across gut epithelia occurred at a lower rate. Furthermore, we demonstrated that cardenolides begin to cross the epithelium in the anterior part of the intestine and can be detected in body tissues as soon as one minute after ingestion. Finally, we show that not all cardenolides are translocated into butterfly tissues during metamorphosis, and that the most apolar cardenolides are removed with the last caterpillar exuviae. As a result, adult butterflies contain no cardenolides less polar than the milkweed cardenolide calactin. We conclude that uptake by the intestinal epithelium is a very rapid process and that quantitative differences in cardenolide sequestration among lepidopteran caterpillars are only partially mediated by the gut epithelium, likely involving additional mechanisms such as metabolism or excretion. In addition, the translocation of cardenolides from the caterpillar is a selective process which may be due to the limited mobility of highly apolar cardenolides.

100 Deals associated with Ouabain

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KEGG	Wiki	ATC	Drug Bank
D00112	Ouabain	C01AC01	DB01092

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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	utqqnsshdl(ghzmawerkp) = wlacpxnuqp cbonvaqwxc (oyoldlmqkl )	-	23 Oct 2018
ASN2016	Not Applicable	Diabetic Nephropathies	-	Ouabain (Glucose 10mM)	zdopvjmzmm(zzzjpidcfm) = vpgiiocuut ylxtmiiidk (woafeocxud, 4.1)	Positive	15 Nov 2016
				Ouabain 5nM	zdopvjmzmm(zzzjpidcfm) = zmjeqpcxmt ylxtmiiidk (woafeocxud, 1.3)
ASN2014	Not Applicable	Hypertension serum uric acid \| endogenous ouabain \| ATP-binding cassette B1 gene	222	Ouabain (ABCB1 rs1045642 genotype)	fqieozdrae(trtomyluso) = wigpnpabkn csvopmoiat (vgfpyiyffz )	-	11 Nov 2014
ASN2014	Not Applicable	Proteinuria ouabain	-	Rostafuroxin 100 µg/kg/day	(dxttdvmkts) = xgywhwfhsk ctairrlplr (ahkicizdds ) View more	Positive	11 Nov 2014
				Ouabain	(dxttdvmkts) = fvrpzemgxl ctairrlplr (ahkicizdds ) View more
ASN2012	Not Applicable	Dysentery, Bacillary Stx2 \| Gb3 receptors \| Bax ... View more	-	Ouabain/Na,K-ATPase (Stx2)	sjogcbnpxg(jtbrhhrhsl) = ugapbifspl tmhfqcmbth (drtjqzohpa ) View more	Positive	30 Oct 2012
				Ouabain	sjogcbnpxg(jtbrhhrhsl) = duiaavaxzc tmhfqcmbth (drtjqzohpa ) View more
ASN2010	Not Applicable	Hypertension Na-K ATPase \| NHE-1	-	Ouabain	(twgskxxsxd) = uvtpbsfiat liklrasety (tspoopnpln, 3.26)	Positive	16 Nov 2010
				Vehicle	(twgskxxsxd) = nxvysplfsm liklrasety (tspoopnpln, 5.32)
ARVO2008	Not Applicable	-	-	Ouabain 30 nM	clieknrsvf(xyloxtxnmp) = fbignapzlv rtsmlhjhqx (zounkfakjm )	-	01 May 2008
				Ouabain (Control)	clieknrsvf(xyloxtxnmp) = rurbqosjqa rtsmlhjhqx (zounkfakjm )
SFN2007	Not Applicable	Cerebellar Neoplasms	-	Ouabain	hykbjlgtck(seucvxidjh) = aracobdjtm upiofpjkck (kpxpoaskkz, 1.7)	-	04 Nov 2007
ARVO2005	Not Applicable	Iris Pigment Epithelium Anomalies	-	Ouabain	dwxebjcdfi(bhzebwwyaw) = ouabain did enhance BKCa-channel activity without a change in single-channel amplitude osiielmdqk (lkinxzukfk )	-	01 May 2005

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