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1. Tissue and salinity specific Na+/Cl− cotransporter (NCC) orthologues involved in the adaptive osmoregulation of sea lamprey (Petromyzon marinus)

   https://doi.org/10.1038/s41598-021-02125-1  

   Barany, A. ; Shaughnessy, C. A. ; Pelis, R. M. ; Fuentes, J. ; Mancera, J. M. ; McCormick, S. D. ( November 2021 , Scientific Reports)

   Two orthologues of the gene encoding the Na⁺-Cl⁻cotransporter (NCC), termednccaandnccb, were found in the sea lamprey genome. No gene encoding the Na⁺-K⁺-2Cl⁻cotransporter 2 (nkcc2) was identified. In a phylogenetic comparison among other vertebrate NCC and NKCC sequences, the sea lamprey NCCs occupied basal positions within the NCC clades. In freshwater,nccamRNA was found only in the gill andnccbonly in the intestine, whereas both were found in the kidney. IntestinalnccbmRNA levels increased during late metamorphosis coincident with salinity tolerance. Acclimation to seawater increasednccbmRNA levels in the intestine and kidney. Electrophysiological analysis of intestinal tissue ex vivo showed this tissue was anion absorptive. After seawater acclimation, the proximal intestine became less anion absorptive, whereas the distal intestine remained unchanged. Luminal application of indapamide (an NCC inhibitor) resulted in 73% and 30% inhibition of short-circuit current (I_sc) in the proximal and distal intestine, respectively. Luminal application of bumetanide (an NKCC inhibitor) did not affect intestinal I_sc. Indapamide also inhibited intestinal water absorption. Our results indicate that NCCb is likely the key ion cotransport protein for ion uptake by the lamprey intestine that facilitates water absorption in seawater. As such, the preparatory increases in intestinalnccbmRNA levels during metamorphosis of sea lamprey are likely critical to development of whole animal salinity tolerance.

    

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2. 11-Deoxycortisol controls hydromineral balance in the most basal osmoregulating vertebrate, sea lamprey (Petromyzon marinus)

   https://doi.org/10.1038/s41598-020-69061-4  

   Shaughnessy, Ciaran A. ; Barany, Andre ; McCormick, Stephen D. ( July 2020 , Scientific Reports)

   It is unknown whether and how osmoregulation is controlled by corticosteroid signaling in the phylogenetically basal vertebrate group Agnatha, including lampreys and hagfishes. It is known that a truncated steroid biosynthetic pathway in lampreys produces two predominant circulating corticosteroids, 11-deoxycortisol (S) and 11-deoxycorticosterone (DOC). Furthermore, lampreys express only a single, ancestral corticosteroid receptor (CR). Whether S and/or DOC interact with the CR to control osmoregulation in lampreys is still unknown. We examined the role of the endogenous corticosteroids in vivo and ex vivo in sea lamprey (Petromyzon marinus) during the critical metamorphic period during which sea lamprey increase osmoregulatory capacity and acquire seawater (SW) tolerance. We demonstrate in vivo that increases in circulating [S] and gill CR abundance are associated with increases in osmoregulatory capacity during metamorphosis. We further show that in vivo and ex vivo treatment with S increases activity and expression of gill active ion transporters and improves SW tolerance, and that only S (and not DOC) has regulatory control over active ion transport in the gills. Lastly, we show that the lamprey CR expresses an ancestral, spironolactone-as-agonist structural motif and that spironolactone treatment in vivo increases osmoregulatory capacity. Together, these results demonstrate that S is an osmoregulatory hormone in lamprey and that receptor-mediated discriminative corticosteroid regulation of hydromineral balance is an evolutionarily basal trait among vertebrates.

    

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3. Transcriptional regulation of esophageal, intestinal, and branchial solute transporters by salinity, growth hormone, and cortisol in Atlantic salmon

   https://doi.org/10.1002/jez.2766  

   Breves, Jason P. ; Runiewicz, Ellie R. ; Richardson, Sierra G. ; Bradley, Serena E. ; Hall, Daniel J. ; McCormick, Stephen D. ( November 2023 , Journal of Experimental Zoology Part A: Ecological and Integrative Physiology)

   In marine habitats, Atlantic salmon (Salmo salar) imbibe seawater (SW) to replace body water that is passively lost to the ambient environment. By desalinating consumed SW, the esophagus enables solute‐linked water absorption across the intestinal epithelium. The processes underlying esophageal desalination in salmon and their hormonal regulation during smoltification and following SW exposure are unresolved. To address this, we considered whether two Na⁺/H⁺exchangers (Nhe2 and −3) expressed in the esophagus contribute to the uptake of Na⁺from lumenal SW. There were no seasonal changes in esophagealnhe2or−3expression during smoltification; however,nhe3increased following 48 h of SW exposure in May. Esophagealnhe2, −3, andgrowth hormone receptor b1were elevated in smolts acclimated to SW for 2.5 weeks. Treatment with cortisol stimulated branchial Na⁺/K⁺‐ATPase (Nka) activity, andNa⁺/K⁺/2Cl⁻cotransporter 1(nkcc1),cystic fibrosis transmembrane regulator 1 (cftr1), andnka‐α1bexpression. Esophagealnhe2, but notnhe3expression, was stimulated by cortisol. In anterior intestine, cortisol stimulatednkcc2, cftr2, andnka‐α1b. Our findings indicate that salinity stimulates esophagealnhe2and−3, and that cortisol coordinates the expression of esophageal, intestinal, and branchial solute transporters to support the SW adaptability of Atlantic salmon.

    

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4. Dehydroepiandrosterone Heightens Aggression and Increases Androgen Receptor and Aromatase mRNA Expression in the Brain of a Male Songbird

   https://doi.org/10.1111/jne.12443  

   Wacker, D. W. ; Khalaj, S. ; Jones, L. J. ; Champion, T. L. ; Davis, J. E. ; Meddle, S. L. ; Wingfield, J. C. ( December 2016 , Journal of Neuroendocrinology)

   Dehydroepiandrosterone (DHEA) is a testosterone/oestrogen precursor and known modulator of vertebrate aggression. Male song sparrows (Melospiza melodia morphna) show high aggression during breeding and nonbreeding life‐history stages when circulatingDHEAlevels are high, and low aggression during molt whenDHEAlevels are low. We previously showed that androgen receptor and aromatasemRNAexpression are higher during breeding and/or nonbreeding in brain regions associated with reproductive and aggressive behaviour, although the potential role ofDHEAin mediating these seasonal changes remained unclear. In the present study, nonbreeding male song sparrows were captured and held in the laboratory under short days (8 : 16 h light/dark cycle) and implanted with s.c.DHEA‐filled or empty (control) implants for 14 days.DHEAimplants increased aggression in a laboratory‐based simulated territorial intrusion. Brains ofDHEA‐implanted birds showed higher aromatasemRNAexpression in the preoptic area (POA) and higher androgen receptormRNAexpression in the periventricular nucleus of the medial striatum (pvMSt) and ventromedial nucleus of the hypothalamus. TheDHEA‐induced increases in aromatase expression in thePOAand androgen receptor expression in the pvMSt are consistent with previously reported seasonal increases in these markers associated with naturally elevatedDHEAlevels. This suggests thatDHEAfacilitates seasonal increases in aggression in nonbreeding male song sparrows by up‐regulating steroid signalling/synthesis machinery in a brain region‐specific fashion.

    

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5. Lipin1 plays complementary roles in myofibre stability and regeneration in dystrophic muscles

   https://doi.org/10.1113/JP284085  

   Jama, Abdulrahman ; Alshudukhi, Abdullah A. ; Burke, Steve ; Dong, Lixin ; Kamau, John Karanja ; Voss, Andrew Alvin ; Ren, Hongmei ( February 2023 , The Journal of Physiology)

   Duchenne muscular dystrophy (DMD) is a severe muscle wasting disorder caused by dystrophin mutations, leading to the loss of sarcolemmal integrity, and resulting in progressive myofibre necrosis and impaired muscle function. Our previous studies suggest that lipin1 is important for skeletal muscle regeneration and myofibre integrity. Additionally, we discovered that mRNA expression levels of lipin1 were significantly reduced in skeletal muscle of DMD patients and the mdx mouse model. To understand the role of lipin1 in dystrophic muscle, we generated dystrophin/lipin1 double knockout (DKO) mice, and compared the limb muscle pathology and function of wild‐type B10, muscle‐specific lipin1 deficient (lipin1^Myf5cKO), mdx and DKO mice. We found that further knockout of lipin1 in dystrophic muscle exhibited a more severe phenotype characterized by increased necroptosis, fibrosis and exacerbated membrane damage in DKO compared to mdx mice. In barium chloride‐induced muscle injury, both lipin1^Myf5cKOand DKO showed prolonged regeneration at day 14 post‐injection, suggesting that lipin1 is critical for muscle regeneration.In situcontractile function assays showed that lipin1 deficiency in dystrophic muscle led to reduced specific force production. Using a cell culture system, we found that lipin1 deficiency led to elevated expression levels of necroptotic markers and medium creatine kinase, which could be a result of sarcolemmal damage. Most importantly, restoration of lipin1 inhibited the elevation of necroptotic markers in differentiated primary lipin1‐deficient myoblasts. Overall, our data suggests that lipin1 plays complementary roles in myofibre stability and muscle function in dystrophic muscles, and overexpression of lipin1 may serve as a potential therapeutic strategy for dystrophic muscles.image

   We identified that lipin1 mRNA expression levels are significantly reduced in skeletal muscles of Duchenne muscular dystrophy patients and mdx mice.

   We found that further depletion of lipin1 in skeletal muscles of mdx mice induces more severe dystrophic phenotypes, including enhanced myofibre sarcolemma damage, muscle necroptosis, inflammation, fibrosis and reduced specific force production.

   Lipin1 deficiency leads to elevated expression levels of necroptotic markers, whereas restoration of lipin1 inhibits their expression.

   Our results suggest that lipin1 is functionally complementary to dystrophin in muscle membrane integrity and muscle regeneration.

    

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