Central injection of caspase inhibitors facilitates the formation of freezing behavior in rats.

We studied the effects of central administration of pancaspase inhibitor z-VAD-fmk and specific caspase 3 inhibitor z-DEVD-fmk on learning and memory in rats. The inhibitors selectively facilitated the formation of freezing behavior without modulating consolidation and retrieval of passive defense behavior in the model of conditioned freezing.

Biochemical markers of apoptosis in different parts of the brain during learning.

Caspase-3 activity and the levels of DNA fragments of 200-600 and >4000 b.p. were estimated in the cerebellar vermis, the hippocampus, and the prefrontal cortex of the brains of adult rats four and 24 months after training to extinction of the acoustic startle reaction and conditioned fear. Differently timed changes in the levels of biochemical markers of apoptosis were seen to different extents in these brain areas after training. These changes were characterized by a decrease in caspase-3 activity in the cerebellar vermis and the hippocampus, with decreases in DNA fragmentation in the hippocampus and cerebral cortex and increases in measures of programmed cell death in the hypothalamus. These experimental data support the view that the apoptosis of cells in the mature brain is involved in the mechanisms of learning and memory.

Liposomes containing dopamine entrapped in response to transmembrane ammonium sulfate gradient as carrier system for dopamine delivery into the brain of parkinsonian mice.

The active loading of liposomes with dopamine in response to an ammonium sulfate gradient was studied. This method can be regarded as a mean to more efficiently improve the liposomal dopamine/lipids ratio in comparison to conventional methods of liposome preparation. Trapping efficiency of dopamine into liposomes exhibiting a transmembrane ammonium sulfate gradient was shown to be dependent on liposome lipid composition, lipid concentration and temperature. Dopamine-containing liposomes with alpha-tocopherol in the lipid bilayer were shown to be stable at least for three weeks. It has been found that intraperitoneal (i.p.) administration of conventionally prepared dopamine-containing liposomes as well as liposomes with increased dopamine/lipid ratio may efficiently suppress the expression of parkinsonian symptoms in C57BL/6 mice with experimental parkinsonian syndrome. On the other hand, only through increasing of liposomal dopamine/lipid ratio the complete compensation of dopamine deficiency in the mice brain was achieved. The obtained data may be considered as biochemical evidence in favor of liposomes' ability to act as a carrier system for the delivery of dopamine into the brain.