Effects of Calcitriol Supplementation on the Hematological Parameters of Sleep Deprived Wistar Rats

The present study investigates the hematologic effect of Calcitriol on rats undergoing sleep deprivation. Male Wistar rats were treated with Calcitriol 120 ng/kg and subjected to sleep deprivation for four successive days. Twenty four hour after last injection, animals were sacrificed and blood was collected for haematological analysis. A four-day sleep restriction caused a decline in total white cell count and increased mean cell hemoglobin and mean cell volume. Furthermore, red blood cell count, packed cell volume, hemoglobin concentration and mean cell hemoglobin concentration also declined in sleep deprived rats. Peripheral blood cell examination revealed that these effects were mild in rats treated with calcitriol. Our findings showed that a four-day paradoxical sleep restriction altered the biochemical integrity of erythrocytes. The observed immunosuppressive effects of sleep deprivation were reversed by exogenous vitamin D supplement, calcitriol. However, only the functional haemoglobin component of red cells was enhanced by a high dose of calcitriol which appears unbeneficial for other units of the erythroid-forming processes. It is therefore possible that the erythrocytic enhancing power of calcitriol is dose dependent and we suggest that lower doses (<120ng/kg) may be required to produce beneficial effects on erythropoiesis

Behavioral effects of D3 receptor inhibition and 5-HT4 receptor activation on animals undergoing chronic cannabinoid exposure during adolescence

Circadian clocks in health and diseas

Anti-HIV drugs promote β-amyloid deposition and impair learning and memory in BALB/c mice

Objectives:Growing evidence suggested that antiretroviral drugs (ARV) may promote β-amyloid accumulation in HIV-1-infected brain and the persistence of HIV-associated neurocognitive disorders (HAND). It has also been shown that lipid peroxidation upregulates β-site APP-cleaving enzyme 1 (BACE1) expression and subsequent promote β-amyloid peptide production. In the present study, we examined whether chronic exposure to the anti-HIV drugs tenofovir disoproxil fumarate and nevirapine induces lipid peroxidation thereby promoting BACE1 and β-amyloid generation and consequently impair cognitive function in mice.Methods:Tenofovir disoproxil fumarate or nevirapine were orally administered to female BALB/c mice once a day for 8 weeks. On the 7th week of treatment, spatial learning and memory were assessed using the Morris water maze test. The levels of lipid peroxidation, β-site APP cleaving enzyme 1 (BACE1), β-amyloid 1-42 and β-amyloid (Aβ) deposits were measured in the hippocampal tissue upon completion of treatment.Results:Chronic administration of nevirapine induced spatial learning and memory impairment in the Morris water maze test, whereas tenofovir disoproxil fumarate did not have an effect. Tenofovir disoproxil fumarate and nevirapine administration increased hippocampal lipid peroxidation and β-amyloid 1-42 concentration. Nevirapine further upregulated BACE1 expression and β-amyloid (Aβ) deposits.Conclusion:Our results suggest that chronic exposure to tenofovir disoproxil fumarate and nevirapine contributes to hippocampal lipid peroxidation and β-amyloid accumulation, respectively, as well as spatial learning and memory deficits in mice even in the absence HIV-infection. These findings further support a possible link between antiretroviral drug toxicity, β-amyloid accumulation and the persistence of HIV associated neurocognitive disorders

Molecular Basis of Cannabis-Induced Schizophrenia-Relevant Behaviours: Insights from Animal Models

Introduction: Cannabis use is a well-established component risk factor for schizophrenia; however, the mechanisms by which cannabis use increases schizophrenia risk are unclear. Animal models can elucidate mechanisms by which chronic cannabinoid treatment can induce schizophrenia-relevant neural changes, in a standardised manner often not possible using patient-based data. Methods: We review recent literature (within the past 10 years) using animal models of chronic and subchronic treatment with cannabinoids which target the cannabinoid 1 receptor [i.e. ∆9-tetrahydrocannabinol, CP55,940 and WIN55,212-2]. Schizophrenia-relevant behavioural consequences of chronic cannabinoid treatment are first briefly summarised, followed by a detailed account of changes to several receptor systems [e.g. cannabinoid, dopaminergic, glutamatergic, γ-aminobutyric acid (GABAe)rgic, serotonergic, noradrenergic], dendritic spine morphology and inflammatory markers following chronic cannabinoids. We distinguish between adolescent and adult cannabinoid treatments, to determine if adolescence is a period of susceptibility to schizophrenia-relevant molecular changes. Results: Chronic cannabinoid treatment induces behaviours relevant to positive, negative and cognitive symptoms of schizophrenia. Chronic cannabinoids also cause region- and subtype-specific changes to receptor systems (e.g. cannabinoid, dopaminergic, glutamatergic, GABAergic), as well as changes in dendritic spine morphology and upregulation of inflammatory markers. These changes often align with molecular changes observed in post-mortem tissue from schizophrenia patients and correspond with schizophrenia-relevant behavioural change in rodents. There is some indication that adolescence is a period of susceptibility to cannabinoid-induced schizophrenia-relevant neural change, but more research in this field is required to confirm this hypothesis. Conclusions: Animal models indicate several molecular mechanisms by which chronic cannabinoids contribute to schizophrenia-relevant neural and behavioural change. It is likely that a number of these mechanisms are simultaneously impacted by chronic cannabinoids, thereby increasing schizophrenia risk in individuals who use cannabis. Understanding how cannabinoids can affect several molecular targets provides critical insight into the complex relationship between cannabis use and schizophrenia risk