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1.
Diabetes & Metabolism Journal ; : 317-326, 2011.
Article in English | WPRIM | ID: wpr-210390

ABSTRACT

Several polymers were used to delivery genes to diabetic animals. Polyaminobutyl glycolic acid was utilized to deliver IL-10 plasmid DNA to prevent autoimmune insulitis of non-obese diabetic (NOD) mouse. Polyethylene glycol grafted polylysine was combined with antisense glutamic acid decarboxylase (GAD) MRNA to represent GAD autoantigene expression. GLP1 and TSTA (SP-EX4) were delivered by bioreducible polymer to stop diabetic progression. Fas siRNA delivery was carried out to treat diabetic NOD mice animal.


Subject(s)
Animals , Mice , Antigens, Neoplasm , DNA , Glutamate Decarboxylase , Glycolates , Histocompatibility Antigens , Interleukin-10 , Mice, Inbred NOD , Plasmids , Polyethylene Glycols , Polylysine , Polymers , RNA, Messenger , RNA, Small Interfering , Transplants
2.
Braz. j. med. biol. res ; 42(11): 1068-1075, Nov. 2009. ilus, tab
Article in English | LILACS | ID: lil-529099

ABSTRACT

Female rats are intensely affected by cocaine, with estrogen probably playing an important role in this effect. Progesterone modulates the GABA system and attenuates the effects of cocaine; however, there is no information about its relevance in changing GABA synthesis pathways after cocaine administration to female rats. Our objective was to investigate the influence of progesterone on the effects of repeated cocaine administration on the isoenzymes of glutamic acid decarboxylase (GAD65 and GAD67) mRNA in brain areas involved in the addiction circuitry. Ovariectomized, intact and progesterone replacement-treated female rats received saline or cocaine (30 mg/kg, ip) acutely or repeatedly. GAD isoenzyme mRNA levels were determined in the dorsolateral striatum (dSTR) and prefrontal cortex (PFC) by RT-PCR, showing that repeated, but not acute, cocaine decreased GADs/β-actin mRNA ratio in the dSTR irrespective of the hormonal condition (GAD65: P < 0.001; and GAD67: P = 0.004). In the PFC, repeated cocaine decreased GAD65 and increased GAD67 mRNA ratio (P < 0.05). Progesterone replacement decreased both GAD isoenzymes mRNA ratio after acute cocaine in the PFC (P < 0.001) and repeated cocaine treatment reversed this decrease (P < 0.001). These results suggest that cocaine does not immediately affect GAD mRNA expression, while repeated cocaine decreases both GAD65 and GAD67 mRNA in the dSTR of female rats, independently of their hormonal conditions. In the PFC, repeated cocaine increases the expression of GAD isoenzymes, which were decreased due to progesterone replacement.


Subject(s)
Animals , Female , Rats , Cocaine/pharmacology , Corpus Striatum/enzymology , Glutamate Decarboxylase/drug effects , Prefrontal Cortex/enzymology , Progesterone/pharmacology , Gene Expression Regulation , Glutamate Decarboxylase/genetics , Rats, Wistar , Reverse Transcriptase Polymerase Chain Reaction , RNA, Messenger/metabolism
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