HINT1 deficiency in aged mice reduces anxiety-like and depression-like behaviours and enhances cognitive performances.

Histidine triad nucleotide-binding protein 1 (HINT1) is regarded as a haplo-insufficient tumour suppressor and is closely associated with many neuropsychiatric disorders, including major depressive disorders. In addition, HINT1 knockout (KO) mice exhibit anxiolytic-like behaviour, antidepression-like behaviour, and enhanced cognitive performance in several studies. However, it is still unclear whether aging contributes to these changes in the emotion and cognition of HINT1 KO mice. This study examined the role of aging in anxiety-like and depression-like behaviours and cognition behaviours in aged HINT1 KO mice compared with young HINT1 KO mice and their wild-type littermates, along with a number of molecular biological methods. In a battery of behavioural tests, aged wild-type mice showed increased anxiety-like and depression-like behaviours and decreased cognitive performance, along with lower expression levels of glutathione peroxidase, enhanced amount of malondialdehyde, and decreased expression levels of brain-derived neurotrophic factor and tyrosine kinase B in the hippocampus and PFC compared to young wild-type mice. HINT1 KO mice showed reduced anxiety-like and depression-like behaviours and enhanced cognitive performance compared to age-matched wild-type mice. In addition, HINT1 KO mice also showed increased GSH-Px and superoxide dismutase, and decreased malondialdehyde, together with enhanced BDNF and Trk-B expression in the hippocampus and PFC. However, when compared with young HINT1 KO mice, aged HINT1 KO mice did not show increased anxiety-like and depression-like behaviours. And there are no differences in the expression level of superoxide dismutase, malondialdehyde, BDNF, and Trk-B between aged and young HINT1 KO mice. In summary, HINT1 deficiency can counteract age-related emotion and cognition dysfunction.

The role of HINT1 protein in morphine addiction: An animal model-based study.

Drug addiction is a recurrent, chronic brain disease. The existing treatment methods have limitations, such as poor adherence and inability to completely avoid relapse. Histidine triad nucleotide-binding protein 1 (HINT1) is involved in many neuropsychiatric diseases, such as schizophrenia, pain, and drug dependence. Studies have confirmed that there is a genetic link between HINT1 and addictions such as nicotine and cocaine. However, there is no research on the role of HINT1 protein in morphine addiction at home and abroad. Thus, we designed this project by constructing different types of morphine addiction animal models, including conditioned place preference and behavioral sensitization. We comprehensively examined the participation of HINT1 protein in key brain regions associated with addiction, including prefrontal cortex, nucleus accumbens, corpus striatum, and hippocampus, in different stages of different models. In addition, we used HINT1 knockout mice to establish the above models and physical dependence model to investigate the effect of HINT1 protein deletion on morphine addiction-related behaviors. We found that HINT1 has varying degrees of involvement in different stages of multiple addictive animal models. The absence of HINT1 can attenuate morphine-mediated addictive behavior to a certain extent and can alleviate the withdrawal symptoms of morphine.

The role of HINT1 in methamphetamine-induced behavioral sensitization.

BACKGROUND: Drug addiction is a chronically relapsing disorder in humans yet the underlying mechanism remained unclear. Recent studies suggested that histidine triad nucleotide binding protein1 (HINT1) may play significant roles in diverse neuropsychiatric diseases including drug addiction. METHODS: In the current study, we used different batches of mice to establish different stages of methamphetamine (METH)-induced behavioral sensitization (BS) to explore the dynamic changes throughout the process of addiction in different brain regions, including the prefrontal cortex (PFC), nucleus accumbens (NAc), caudate putamen (CPu), and hippocampus (Hip). In addition, we used HINT1 knockout (KO) mice to investigate the effect of HINT1 protein deletion on METH-induced BS. RESULTS: We found that in PFC of the METH group mice, the HINT1 expression level initially increased after development phase, and then dropped to the normal level during expression phase. However, there was no statistical difference in the HINT1 expression level in the other three encephalic regions (NAc, CPu, and Hip). The absence of HINT1 could promote METH-mediated addictive behavior to a certain extent, while the significant difference between genotypes only occurred in the development phase. CONCLUSIONS: Using the new technique, hip fractures were correctly predicted in 78% of cases compared with 36% when using the T-score. The accuracy of the prediction was not greatly reduced when using SSM and SAM (78% and 74% correct, respectively). Various geometric and BMD distribution traits were identified in the fractured and non-fractured groups.

Does genetic mouse model of constitutive Hint1 deficiency exhibit schizophrenia-like behaviors?

The histidine triad nucleotide binding protein 1 (HINT1) is closely related to many neuropsychiatric disorders. Clinical studies supported that mutations in the Hint1 gene correlated potentially with schizophrenia. In addition, Hint1 gene knockout (KO) mice exhibited hyperactivity induced by amphetamine and apomorphine. However, it is still unclear whether this animal model exhibits schizophrenia-like behaviors and, if so, their underlying mechanisms remain to be elucidated. Thus, our study sought to evaluate schizophrenia-like behaviors in Hint1-KO mice, and explore the associated changes in neuronal structural plasticity and schizophrenia-related molecules. A series of behavioral tests were used to compare Hint1-KO and their wild-type (WT) littermates, alongside a number of morphological and molecular biological methods. Relative to WT mice, Hint1-KO mice exhibited reduced social interaction behaviors, aggressive behavior, sensorimotor gating deficits, apathetic and self-neglect behaviors, and increased MK-801-induced hyperactivity. Hint1-KO mice also showed partly increased dendritic complexity in the hippocampus (Hip) relative to WT mice. Total glutamate was decreased in the medial prefrontal cortex, nucleus accumbens (NAc), and Hip of KO mice. Expression of NR1, NR2A, and D4R was decreased whereas that of D1R was increased in the NAc of KO relative to WT mice. The expression level of NR2B was increased whereas that of D1R was decreased in the Hip of KO mice. Hint1-KO mice exhibited schizophrenia-like behaviors. Partly increased dendritic complexity and dysfunction in both the dopaminergic and glutamatergic systems may be involved in the abnormalities in Hint1-KO mice.

[Clinical utility of reticulocyte hemoglobin content for the diagnosis of iron deficiency anemia in children].

OBJECTIVE: To study the clinical utility of measuring reticulocyte hemoglobin content (CHr) in the diagnosis of iron deficiency anemia (IDA) in children. METHODS: One hundred children with IDA at ages of 1 to 6 years and 50 healthy children were enrolled. Red blood cell parameters, CHr, hemoglobin (Hb), red blood count (RBC) and mean corpusular volume (MCV), were determined using the Blood Cell Analyzer. Serum ferritin (SF) levels were determined using radioimmunoassay double antibody techique. Soluble serum transferrin (sTfR) levels were determined using ELISA. RESULTS: The values of Hb (100 ± 6 g/L vs 126 ± 8 g/L) and CHr (18 ± 5 pg vs 31 ± 3 pg) in the IDA group were significantly lower than normal controls (P<0.01). SF levels (11 ± 4 µg/L) in the IDA group were also lower than normal controls (59 ± 36 µg/L) (P<0.01). In contrast, the values of sTfR in the IDA group were significantly higher than normal controls (4.8 ± 2.1 mg/L vs 1.4 ± 0.6 mg/L; P<0.01). In both groups, there was a positive correlation between the values of CHr and Hb [r=0.540 (control group), r=0.734 (IDA group); P<0.01]. In the IDA group, CHr was positively correlated with SF(r=0.464; P<0.01) and negatively correlated with sTfR(r=-0.450; P<0.01). When the cut-off value of CHr was 27.8 pg, the sensitivity and specificity for the diagnosis of IDA were 88.0% and 90.0%, respectively and the area under the ROC curve was 0.948. CONCLUSIONS: CHr can be used as an index for the diagnosis of IDA in children.