Orphan nuclear receptor nr4a1 regulates winter depression-like behavior in medaka.

About 10% of the population suffers from depression in winter at high latitude. Although it has become a serious public health issue, its underlying mechanism remains unknown and new treatments and therapies are required. As an adaptive strategy, many animals also exhibit depression-like behavior in winter. Previously, it has been reported that celastrol, a traditional Chinese medicine, can rescue winter depression-like behavior in medaka, an excellent model of winter depression. Nuclear receptor subfamily 4 group A member 1 (nr4a1, also known as nur77) is a known target of celastrol, and the signaling pathway of nr4a1 was suggested to be inactive in medaka brain during winter, implying the association of nr4a1 and winter depression-like behavior. However, the direct evidence for its involvement in winter depression-like behavior remains unclear. The present study found that nr4a1 was suppressed in the medaka brain under winter conditions. Cytosporone B, nr4a1 chemical activator, reversed winter depression-like behavior under winter conditions. Additionally, nr4a1 mutant fish generated by CRISPR/Cas9 system showed decreased sociability under summer conditions. Therefore, our results demonstrate that the seasonal regulation of nr4a1 regulates winter depression-like behavior and offers potential therapeutic target.

Coadsorption of trivalent metal ions and anions on strongly acidic cation-exchange resins by bridge bonding.

The effects of anions (P(V), P(III), P(I), Se(IV), OH(-), F(-), Cl(-), SCN(-), S(IV), and CH(3)COO(-)) on the adsorption of trivalent metal ions (Fe(3+), Al(3+), Ga(3+), In(3+), and Sc(3+)) to three strongly acidic cation-exchange resins (-S)(-) of different types (porous or gel) and different exchange capacities (4.55, 3.91, and 0.96 mmol g(-1)) were studied systematically. All these metal ions showed coadsorption of OH(-), irrespective of the resins. In contrast, coadsorption of P(V), P(III), P(I), and Se(IV) was observed on the resins of the higher exchange capacities but not on the resin of the lowest exchange capacity. Stoichiometric analyses and spectroscopic (Mossbauer and infrared) studies for Fe(3+) demonstrated the presence of the coadsorbed species: [(-S)(2)Fe(OH)] and [(-S)(2)(Fe-O-Fe)(S-)(2)] for OH(-), [(-S)(2)Fe(HPO(4))Fe(S-)(2)] for P(V), and [(-S)(2)FeX](j) (X(-) = H(2)PO(3)(-), H(2)PO(2)(-), HSeO(3)(-); j > 1) for P(III), P(I), and Se(IV). No coadsorption was observed for the other anions. These findings indicate that the bridge bonding of anions between the metal ions adsorbed on the resins of the higher exchange capacities plays a crucial role for the coadsorption. Some analytical implication was also discussed.