DOPAMINE D2 RECEPTOR MECHANISMS CONTRIBUTE TO AGE-RELATED COGNITIVE DECLINE - THE EFFECTS OF QUINPIROLE ON MEMORY AND MOTOR-PERFORMANCE IN MONKEYS

The D2 dopamine (DA) receptor agonist, quinpirole, was characterized in young adult monkeys, young reserpine-treated monkeys and aged monkeys to assess the contribution of DA to age-related loss of prefrontal cortical (PFC) cognitive function, Monkeys were tested on a delayed response memory task that depends on the PFC, and a fine motor task that taps the functions of the motor cortex, In young adult monkeys, low quinpirole doses impaired performance of the PFC and fine motor tasks, while higher doses improved memory performance and induced dyskinesias and ''hallucinatory-like'' behaviors. The pattern of the quinpirole response in reserpine-treated monkeys suggested that the impairments in delayed response and fine motor performance resulted from drug actions at D2 autoreceptors, while the improvement in delayed response performance, dyskinesias and ''hallucinatory-like'' behaviors resulted from actions at postsynaptic receptors. In aged monkeys, low doses of quinpirole continued to impair fine motor performance, but lost their ability to impair delayed response performance. The magnitude of cognitive improvement and the incidence of ''hallucinatory-like'' behaviors were also reduced in the aged animals, suggesting some loss of postsynaptic D2 receptor function, The pattern of results is consistent with the greater loss of DA from the PFC than from motor areas in aged monkey brain (Goldman-Rakic and Brown, 1981; Wenk et al., 1989), and indicates that DA depletion contributes significantly to age-related cognitive decline.

Novel hybrid periodic mesoporous organosilica material grafting with Tb complex: Synthesis, characterization and photoluminescence property

A novel periodic mesoporous organosilica (PMO) material was synthesized through one-step co-condensation of 1,2-bis(triethoxysilyl)ethane (BTESE) and benzoic acid-functionalized organosilane (BA-Si) using cetyltrimethylammonium bromide (CTAB) as a structure-directing agent under basic conditions. The materials were fully characterized by FTIR, XRD, N-2 adsorption-desorption isotherms and FESEM. FTIR spectra proved that BA-Si was successfully incorporated into the PMO materials (PMOs) via benzyl group as a linker. XRD and N-2 adsorption-desorption isotherms revealed the characteristic mesoporous structure with highly uniform pore size distributions. FESEM confirmed that the morphology of the PMOs was significantly dependent cri the molar ratio of two organosilica precursors.

Comparison between Gd-DTPA and several bisamide derivatives as potential MRI contrast agents

Four neutral gadolinium complexes of diethylenetriaminepentaacetic acid (DTPA)-bisamide derivatives have been synthesized and characterized. Their potential application as tissue-specific and low-osmolarity MRI contrast agents has been evaluated by in vitro and in vivo experiments. Their measured relaxivities in D2O, bovine serum albumin and human serum transferrin solutions showed favorable relaxation ability. In vivo studies have proven that Gd(DTPA-BDMA), Gd(DTPA-BIN), and Gd(cyclic-DTPA-1,2-pn) could be promising liver-specific MRI contrast agents and Gd(DTPA-BDMA), and Gd(cyclic-DTPA-1,2-pn) have favorable renal excretion capability. Among them, Gd(cyclic-DTPA-1,2-pn) is a more powerful hepatic contrast agent and Gd(DTPA-BIN) provides the stable imaging contrast for several hours. They also show a lower toxicity.

In situ electrochemical scanning tunnelling microscopy investigation of structure for horseradish peroxidase and its electrocatalytic property

Immobilization of protein molecules is a fundamental problem for scanning tunnelling microscopy (STM) measurements with high resolution. In this paper, an electrochemical method has been proved to be an effective way to fix native horseradish peroxidase (HRP) as well as inactivated HRP from electrolyte onto a highly oriented pyrolytic graphite (HOPG) surface. This preparation is suitable for both ex situ and in situ electrochemical STM (ECSTM) measurements. In situ STM has been successfully employed to observe totally different structures of HRP in three typical cases: (1) in situ ECSTM reveals an oval-shaped pattern for a single molecule in neutral buffer solution, which is in good agreement with the dimension determined as 6.2 x 4.3 x 1.2. nm(3) by ex situ STM for native HRP; (2) in situ ECSTM shows that the adsorbed HRP molecules on HOPG in a denatured environment exhibit swelling globes at the beginning and then change into a V-shaped pattern after 30 min; (3) in situ ECSTM reveals a black hole in every ellipsoidal sphere for inactivated HRP in strong alkali solution. The cyclic voltammetry results indicate that the adsorbed native HRP can directly catalyse the reduction of hydrogen peroxide, demonstrating that a direct electron transfer reduction occurred between the enzyme and HOPG electrode, whereas the corresponding cyclic voltammograms for denatured HRP and inactivated HRP adsorbed on HOPG electrodes indicate a lack of ability to catalyse H2O2 reduction, which confirms that the HRP molecules lost their biological activity. Obviously, electrochemical results powerfully support in situ STM observations.