ABSTRACT
A series of 41 papers by H. Zhong et al. are retracted.
ABSTRACT
AIM: To explore the physiological role of gamma-aminobutyric acid transporter subtype I (GAT1) in cognition. METHODS: Transgenic mice were produced by pronuclei microinjection method. Integration of transgene was identified by Southern-blot and PCR analysis in various generations. Level of GAT1 mRNA in a variety of tissues was evaluated by semi-quantitative RT-PCR analysis. GAT1 protein was detected by immunofluorescence and histochemistry analysis. Associative learning capacity was analyzed by conditioned avoidance task. Memory retention was assessed by novel object recognition test. Morphology of synaptosomes was examined by electron microscope. RESULTS: Four independent founder mice bearing various copies of transgene were generated. GAT1 was evidently overexpressed at both mRNA and protein level in a variety of tissues from transgenic mice. In comparison with wild-type mice, transgenic mice exhibited significantly declined associative learning capacity (P < 0.01) and decreased memory retention (P < 0.01 in 1-h-retention, and P < 0.05 in 1-d-retention). In addition, the amount of asymmetric synapses in the brain of transgenic mice was reduced approximately by 24 %, relative to wild-type mice. CONCLUSION: Overexpression of GAT1 in mice results in cognitive deterioration, indicating that the alteration in the expression of gamma-aminobutyric acid transporters is involved in the pathophysiological mechanism underlying some cognitive deficiencies.
Subject(s)
Carrier Proteins/adverse effects , Cognition Disorders/chemically induced , Membrane Proteins/adverse effects , Membrane Transport Proteins , Organic Anion Transporters , Animals , Avoidance Learning/drug effects , Carrier Proteins/biosynthesis , Carrier Proteins/genetics , GABA Plasma Membrane Transport Proteins , Gene Expression , Membrane Proteins/biosynthesis , Membrane Proteins/genetics , Mice , Mice, Inbred C57BL , Mice, Transgenic , RNA, Messenger/biosynthesis , Retention, Psychology/drug effects , Synaptosomes/pathologyABSTRACT
Familial hypobetalipoproteinemia (FHBL) is an apparently autosomal dominant disorder of lipid metabolism characterized by less than fifth percentile age- and sex-specific levels of apolipoprotein beta (apobeta) and low-density lipoprotein-cholesterol. In a minority of cases, FHBL is due to truncation-producing mutations in the apobeta gene on chromosome 2p23-24. Previously, we reported on a four-generation FHBL kindred in which we had ruled out linkage of the trait to the apobeta gene. To locate other loci containing genes for low apobeta levels in the kindred, a genomewide search was conducted. Regions on 3p21.1-22 with two-point LOD scores >1.5 were identified. Additional markers were typed in the region of these signals. Two-point LOD scores in the region of D3S2407 increased to 3.35 at O = 0. GENEHUNTER confirmed this finding with an nonparametric multipoint LOD score of 7.5 (P=.0004). Additional model-free analyses were conducted with the square root of the apobeta level as the phenotype. Results from the Loki and SOLAR programs further confirmed linkage of FHBL to 3p21.1-22. Weaker linkage to a region near D19S916 was also indicated by Loki and SOLAR. Thus, a heretofore unidentified genetic susceptibility locus for FHBL may reside on chromosome 3.
Subject(s)
Chromosomes, Human, Pair 3/genetics , Genetic Predisposition to Disease/genetics , Hypobetalipoproteinemias/genetics , Adolescent , Aged , Apolipoproteins B/blood , Apolipoproteins B/genetics , Chromosome Mapping , Female , Genetic Markers/genetics , Haplotypes/genetics , Humans , Hypobetalipoproteinemias/blood , Lod Score , Male , Middle Aged , Models, Genetic , Pedigree , Quantitative Trait, Heritable , SoftwareABSTRACT
Using the method of bilateral injection of GABA (100 micrograms/microliters) and muscimol (0.1 micrograms/microliters) into the caudate-putamen nucleus (CPN) we have studied the role of GABA-ergic transmission of CPN in the control of conditioned behavior. In order to compare the effects of GABA and muscimol on two behavioral paradigms, rats of either sex weighing 160-180 g were trained to perform discrimination learning and conditioned avoidance response. A tone (1 kHz, 80 dB) was used as a conditioned stimulus. After bilateral injections of GABA and muscimol into the trained rats' CPN respectively, the conditioned avoidance response was inhibited temporarily, whereas the discrimination learning remained almost unchanged. In addition, the inhibitory effect of muscimol on the conditioned avoidance response was attenuated or even abolished by following bilateral intra-CPN injection of picrotoxin (0.1 micrograms/microliters for each side). As a control, the same volume of saline was injected into CPN bilaterally, and it showed that there was no change of both the conditioned avoidance response and the discrimination learning. The results show that the GABA-ergic transmission of CPN does play a role in the control of avoidance conditioning in rats, and thus support the suggestion that GABA-ergic transmission of the caudate-globus pallidus plays an important role in the control of conditioned behavior.