Prolonged corticosterone exposure induces dendritic spine remodeling and attrition in the rat medial prefrontal cortex.

The stress-responsive hypothalamo-pituitary-adrenal (HPA) axis plays a central role in promoting adaptations acutely, whereas adverse effects on physiology and behavior following chronic challenges may result from overactivity of this system. Elevations in glucocorticoids, the end-products of HPA activation, play roles in adaptive and maladaptive processes by targeting cognate receptors throughout neurons in limbic cortical networks to alter synaptic functioning. Because previous work has shown that chronic stress leads to functionally relevant regressive alterations in dendritic spine shape and number in pyramidal neurons in the medial prefrontal cortex (mPFC), this study examines the capacity of sustained increases in circulating corticosterone (B) alone to alter dendritic spine morphology and density in this region. Subcutaneous B pellets were implanted in rats to provide continuous exposure to levels approximating the circadian mean or peak of the steroid for 1, 2, or 3 weeks. Pyramidal neurons in the prelimbic area of the mPFC were selected for intracellular fluorescent dye filling, followed by high-resolution three-dimensional imaging and analysis of dendritic arborization and spine morphometry. Two or more weeks of B exposure decreased dendritic spine volume in the mPFC, whereas higher dose exposure of the steroid resulted in apical dendritic retraction and spine loss in the same cell population, with thin spine subtypes showing the greatest degree of attrition. Finally, these structural alterations were noted to persist following a 3-week washout period and corresponding restoration of circadian HPA rhythmicity. These studies suggest that prolonged disruptions in adrenocortical functioning may be sufficient to induce enduring regressive structural and functional alterations in the mPFC. J. Comp. Neurol. 524:3729-3746, 2016. © 2016 Wiley Periodicals, Inc.

Solution and Solid State Properties of [N-(2-Hydroxyethyl)iminodiacetato]vanadium(IV), -(V), and -(IV/V) Complexes(1).

A mononuclear vanadium(IV), a mononuclear vanadium(V), and a binuclear mixed valence vanadium(IV/V) complex with the ligand N-(2-hydroxyethyl)iminodiacetic acid (H(3)hida) have been structurally characterized. Crystal data for [VO(Hhida)(H(2)O)].CH(3)OH (1): orthorhombic; P2(1)2(1)2(1); a= 6.940(2), b = 9.745(3), c= 18.539(4) Å; Z = 4. Crystal data for Na[V(O)(2)(Hhida)(2)].4H(2)O (2): monoclinic; P2(1)/c; a = 6.333(2), b = 18.796(2), c = 11.5040(10) Å; beta = 102.53(2) degrees; Z = 4. Crystal data for (NH(4))[V(2)(O)(2)(&mgr;-O)(Hhida)(2)].H(2)O (3): monoclinic; C2/c; a = 18.880(2), b= 7.395(2), c = 16.010(2) Å; beta = 106.33(2) degrees; Z = 4. The mononuclear vanadium(IV) and vanadium(V) complexes are formed from the monoprotonated Hhida(2)(-) ligand, and their structural and magnetic characteristics are as expected for six-coordinate vanadium complexes. An interesting structural feature in these complexes is the fact that the two carboxylate moieties are coordinated trans to one another, whereas the carboxylate moieties are coordinated in a cis fashion in previously characterized complexes. The aqueous solution properties of the vanadium(IV) and -(V) complexes are consistent with their structures. The vanadium(V) complex was previously characterized; in the current study structural characterization in the solid state is provided. X-ray crystallography and magnetic methods show that the mixed valence complex contains two indistinguishable vanadium atoms; the thermal ellipsoid of the bridging oxygen atom suggests a type III complex in the solid state. Magnetic methods show that the mixed valence complex contains a free electron. Characterization of aqueous solutions of the mixed valence complex by UV/vis and EPR spectroscopies suggests that the complex may be described as a type II complex. The Hhida(2)(-) complexes have some similarities, but also some significant differences, with complexes of related ligands, such as nitrilotriacetate (nta), N-(2-pyridylmethyl)iminodiacetate (pmida), and N-(S)-[1-(2-pyridyl)ethyl]iminodiacetate (s-peida). Perhaps most importantly, the mixed valence Hhida(2)(-) complex is significantly less stable than the corresponding pmida and s-peida complexes of similar overall charge but very similar in stability to the nta and V(2)O(3)(3+) complexes with higher charges. Thus, there is the potential for designing stable mixed valence dimers.

Syntheses, X-ray Structures, and Solution Properties of [V(4)O(4){(OCH(2))(3)CCH(3)}(3)(OC(2)H(5))(3)] and [V(4)O(4){(OCH(2))(3)CCH(3)}(2)(OCH(3))(6)]: Examples of New Ligand Coordination Modes.

Tetranuclear vanadium complexes with alkoxy ligands, [V(4)O(4){&mgr;,&mgr;,&mgr;(3)-(OCH(2))(3)CCH(3)}(2)(OCH(3))(6)] (1) and [V(4)O(4){&mgr;-(OCH(2))(3)CCH(3)}{&mgr;,&mgr;(3)-(OCH(2))(3)CCH(3)}{&mgr;,&mgr;,&mgr;(3)-(OCH(2))(3)CCH(3)}(OR)(3)] (R = C(2)H(5) (2), R = CH(CH(3))(2) (3), R = CH(3) (4)), were synthesized by reacting VO(OR)(3) and H(3)thme (H(3)thme = 1,1,1-tris(hydroxymethyl)ethane) in alcohol. Complex 1 crystallized in the monoclinic space group P2(1)/n with a = 9.646(4) Å, b = 11.502(3) Å, c = 11.960(3) Å, beta = 90.20(3) degrees, V = 1326.9 (7) Å(3), Z = 2 and R (wR(2)) = 0.045 (0.143). Complex 2 also crystallized in the monoclinic space group P2(1)/n with a = 8.290(8) Å, b = 12.237(2) Å, c = 29.118(4) Å, beta = 89.455(9) degrees, V = 2954(3) Å(3), Z = 4, and R(wR(2)) = 0.049 (0.126). Both 1 and 2 are neutral, discrete complexes possessing a common [V(4)O(16)](12)(-) core, which consists of four vanadium(V) atoms chelated by two (1) or three (2) tridentate thme(3)(-) ligands and by six (1) or three (2) RO(-) groups. Compound 1 exhibits a crystallographically required inversion center; in contrast, complex 2 exhibits no crystallographically imposed symmetry, and its three trialkoxy ligands each coordinate differently (one thme(3)(-) is coordinated in a new coordination mode with the oxygens in a terminal, doubly-bridging and triply-bridging mode). Both compounds 1 and 2 maintain their structures in solution, although compound 1 also forms a second minor species upon dissolution. Sequential exchanges of the RO(-) groups in complexes 2 and 3 were investigated by (51)V and (1)H NMR spectroscopy. For example, [V(4)O(4)(thme)(3)(OC(2)H(5))(3)] will react with CH(3)OH to generate [V(4)O(4)(thme)(3)(OCH(3))(3)] (4). These reactions were found to be reversible. The time scale of the alcohol exchange reactions were found to vary depending on the vanadium center that is undergoing the exchange.