Postsynaptic histamine H3 receptors in ventral basal forebrain cholinergic neurons modulate contextual fear memory.

Overly strong fear memories can cause pathological conditions. Histamine H3 receptor (H3R) has been viewed as an optimal drug target for CNS disorders, but its role in fear memory remains elusive. We find that a selective deficit of H3R in cholinergic neurons, but not in glutamatergic neurons, enhances freezing level during contextual fear memory retrieval without affecting cued memory. Consistently, genetically knocking down H3R or chemogenetically activating cholinergic neurons in the ventral basal forebrain (vBF) mimics this enhanced fear memory, whereas the freezing augmentation is rescued by re-expressing H3R or chemogenetic inhibition of vBF cholinergic neurons. Spatiotemporal regulation of H3R by a light-sensitive rhodopsin-H3R fusion protein suggests that postsynaptic H3Rs in vBF cholinergic neurons, but not presynaptic H3Rs of cholinergic projections in the dorsal hippocampus, are responsible for modulating contextual fear memory. Therefore, precise modulation of H3R in a cell-type- and subcellular-location-specific manner should be explored for pathological fear memory.

Antagonism of histamine H3 receptor promotes angiogenesis following focal cerebral ischemia.

Our previous study showed that H3 receptor antagonists reduced neuronal apoptosis and cerebral infarction in the acute stage after cerebral ischemia, but through an action independent of activation of histaminergic neurons. Because enhanced angiogenesis facilitates neurogenesis and neurological recovery after ischemic stroke, we herein investigated whether antagonism of H3R promoted angiogenesis after brain ischemia. Photothrombotic stroke was induced in mice. We showed that administration of H3R antagonist thioperamide (THIO, 10 mg·kg-1·d-1, i.p., from D1 after cerebral ischemia) significantly improved angiogenesis assessed on D14, and attenuated neurological defects on D28 after cerebral ischemia. Compared with wild-type mice, Hrh3-/- mice displayed more blood vessels in the ischemic boundary zone on D14, and THIO administration did not promote angiogenesis in these knockout mice. THIO-promoted angiogenesis in mice was reversed by i.c.v. injection of H3R agonist immepip, but not by H1 and H2 receptor antagonists, histidine decarboxylase inhibitor α-fluoromethylhistidine, or histidine decarboxylase gene knockout (HDC-/-), suggesting that THIO-promoted angiogenesis was independent of activation of histaminergic neurons. In vascular endothelial cells (bEnd.3), THIO (10-9-10-7 M) dose-dependently facilitated cell migration and tube formation after oxygen glucose deprivation (OGD), and H3R knockdown caused similar effects. We further revealed that H3R antagonism reduced the interaction between H3R and Annexin A2, while knockdown of Annexin A2 abrogated THIO-promoted angiogenesis in bEnd.3 cells after OGD. Annexin A2-overexpressing mice displayed more blood vessels in the ischemic boundary zone, which was reversed by i.c.v. injection of immepip. In conclusion, this study demonstrates that H3R antagonism promotes angiogenesis after cerebral ischemia, which is independent of activation of histaminergic neurons, but related to the H3R on vascular endothelial cells and its interaction with Annexin A2. Thus, H3R antagonists might be promising drug candidates to improve angiogenesis and neurological recovery after ischemic stroke.

HIV/AIDS related perception and behavior: A comparative study among college students of different majors in China.

OBJECTIVE: In order to carry out proper education and intervention of AIDS based on different features and demands of different majors, this study aimed to compare the difference of college students from six majors in China in the aspects of AIDS-related knowledge, attitudes and behaviors. METHODS: A questionnaire survey was carried out among 18,644 students in 30 colleges/universities from 9 provinces of China, who were recruited through stratified cluster sampling. AIDS-related knowledge, attitude, condom-use intention, self-efficacy and sexual behavior of these students were investigated. RESULTS: AIDS-related knowledge level of students majoring in education was the lowest while that of medical students was the highest as well as highest self-efficacy of condom use. Students of music or fine arts had the strongest intention to use condoms, while the students majoring in education had the weakest. The sexually active percentages of male students from different majors ranked as follows: music or fine arts (29.5%), minority nationality (12.2%), science & tech (10.9%), medicine (10.6%), education-major (10.0%), and liberal arts (8.2%). Among female students, the rank was music or fine arts (11.0%), science & tech (6.2%), education-major school (4.5%), minority nationality (4.5%), liberal arts (4.1%), and medicine (2.8%). CONCLUSION: It is urgent to enhance proper AIDS-related education and intervention based on the features and demands of students from different majors or universities, for example, to enhance comprehensive AIDS prevention education among students major in education and to increase behavioral skills to prevent sexually transmitted diseases among students from colleges or faculty of music or fine arts.

Predicting Stage of Exercise Among Patients with Type 2 Diabetes: A Test of the Extended Theory of Planned Behavior.

PURPOSE: This study aimed to predict stage of exercise among Chinese patients with type 2 diabetes by using an extended theory of planned behavior model (TPB) incorporating descriptive norm and self-identity. PATIENTS AND METHODS: Participants (N=791) were included in a cross-sectional study. Structural equation modeling was used to explain how the extended TPB could predict the stage of exercise. RESULTS: The model accounted for 41% of the variance in stage of exercise and 81.1% of the variance in intention. Intention (ß=0.359, P<0.01) and self-identity (ß=0.236, P<0.001) had a direct effect on stage of exercise. Self-identity (ß=0.261, P<0.001), descriptive norm (ß=0.035, P<0.05) and PBC (ß=0.683, P<0.001) were strong predicators of intention. The effects of self-identity and PBC on behavior were significantly mediated via intention. Age, BMI and stage of diet behavior were found to be significantly related to intention and behavior. CONCLUSION: This study has tested the usefulness of the extended TPB for explaining exercise in Chinese diabetic patients. To promote patients to start or continue exercising, interventions should target self-identity and controllability for physical activity.

Histamine H1 Receptors in Neural Stem Cells Are Required for the Promotion of Neurogenesis Conferred by H3 Receptor Antagonism following Traumatic Brain Injury.

The neurological recovery following traumatic brain injury (TBI) is limited, largely due to a deficiency in neurogenesis. The present study explores the effects of histamine H3 receptor (H3R) antagonism on TBI and mechanisms related to neurogenesis. H3R antagonism or H3R gene knockout alleviated neurological injury in the late phase of TBI, and also promoted neuroblast differentiation to enhance neurogenesis through activation of the histaminergic system. Histamine H1 receptor, but not H2 receptor, in neural stem cells is shown to be essential for this promotion by using Hrh1fl/fl;NestinCreERT2 and Hrh2fl/fl;NestinCreERT2 mice. Moreover, increase in mature and functional neurons at the penumbra area conferred by H3R antagonism was abrogated in Hrh1fl/fl;NestinCreERT2 mice. Taken together, H3R antagonism provides neuroprotection against TBI in the late phase through the promotion of neurogenesis, and the H1 receptor in neural stem cells is required for this action. H3R may serve as a new target for clinical treatment of TBI.