P-glycoprotein (P-gp) is encoded by the ABCB1 gene and acts as an efflux pump for xenobiotics. In the Border Collie, a nonsense mutation caused by a 4-base pair deletion in the ABCB1 gene is associated with a premature stop to P-gp synthesis. In this study, we examined the full-length coding sequence of the ABCB1 gene in an ivermectin-sensitive Border Collie that lacked the aforementioned deletion mutation. The sequence was compared to the corresponding sequences of a wild-type Beagle and seven ivermectin-tolerant family members of the Border Collie. When compared to the wild-type Beagle sequence, that of the ivermectin-sensitive Border Collie was found to have one insertion mutation and eight single nucleotide polymorphisms (SNPs) in the coding sequence of the ABCB1 gene. While the eight SNPs were also found in the family members' sequences, the insertion mutation was found only in the ivermectin-sensitive dog. These results suggest the possibility that the SNPs are species-specific features of the ABCB1 gene in Border Collies, and that the insertion mutation may be related to ivermectin intolerance.
ATP-Binding Cassette Transporters/*genetics ; Animals ; Depression/chemically induced ; Dogs/*genetics ; Female ; Ivermectin/*adverse effects ; Male ; Mutagenesis, Insertional/*genetics ; Polymorphism, Single Nucleotide/genetics ; Sialorrhea/chemically induced

Microglia-mediated neuroinflammation is widely perceived as a contributor to numerous neurological diseases and mental disorders including depression. Discs large homolog 1 (Dlg1), an adaptor protein, regulates cell polarization and the function of K
Animals ; Depression/chemically induced* ; Inflammation ; Lipopolysaccharides/toxicity* ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Microglia ; NF-kappa B ; Neuroinflammatory Diseases

Frontal meningiomas may present only with psychological symptoms that resemble depression, anxiety states, hypomania and schizophrenia. Herein, we present the case of a 55-year-old man who was initially thought to have depression and bipolar disorder, but was eventually diagnosed with frontal lobe syndrome caused by a giant frontal meningioma.
Alcohol Drinking ; adverse effects ; Bipolar Disorder ; chemically induced ; diagnosis ; Brain Neoplasms ; diagnosis ; surgery ; Depression ; chemically induced ; diagnosis ; Diagnosis, Differential ; Frontal Lobe ; pathology ; Humans ; Male ; Meningeal Neoplasms ; diagnosis ; surgery ; Meningioma ; diagnosis ; surgery ; Middle Aged ; Syndrome

AIMTo investigate the effects of endothelin-1 (ET-1) and nitric oxide (NO) on lipopolysaccharide(LPS)-induced myocardial dysfunction, and explore the related underlying mechanisms.

METHODSExperimental septic model was established by intraperitoneal injection of LPS (10 mg x kg(-1)). The study was carried out on the isolated rat hearts to determine the roles of ET-1 and NO in the effect of LPS on the cardiac contractility and on the isolated rat ventricular myocytes model to observe the [Ca2+]i homeostasis in cardiac myocytes.

RESULTS(1) The levels of serum NO2-/NO3- and plasma ET-1 were markedly increased by LPS treatment for 4 hours. (2) LPS induced the decrease in rate-pressure product (RPP), and increase in left ventricular end-diastolic pressure (LVEDP) in the isolated perfused rat hearts. Pretreatment with either aminoguanidine (AMG) (100 mg x kg(-1), i.p.) or BQ-123 (1 mg x kg(-1), i.p.) partially attenuated LPS-induced myocardial depression. When these two drugs were simultaneously given, myocardial depression elicited by LPS was almost abolished. (3) LPS significantly decreased the amplitude of caffeine induced [Ca2+]i transients compared to the control cells. The activity of SR Ca22+ -ATPase was significantly decreased in the cardiac myocytes from LPS-treated rats. Single pretreatment with either AMG or BQ-123 did not attenuate the impairment of SR Ca2+ -ATPase induced by LPS.

CONCLUSIONET-1 and NO mediate myocardial dysfunction in hearts isolated and decrease [Ca2+]i transients in cardiac myocytes from LPS-treated rats. But neither ET-1 nor NO participates in the impairment of SR Ca2+ -ATPase induced by LPS.

Animals ; Depression, Chemical ; Endothelin-1 ; physiology ; Lipopolysaccharides ; toxicity ; Male ; Myocardial Contraction ; drug effects ; physiology ; Nitric Oxide ; physiology ; Rats ; Rats, Sprague-Dawley ; Shock, Septic ; chemically induced ; physiopathology

OBJECTIVEStriatum may be involved in depressive disorders according to the neuroimaging analysis and clinical data. However, no animal model at present supported the possible role of striatum in the pathogenesis of depression. In the present study, we have investigated the depressive-like behavior in mice recently intoxicated with 3-nitropropionic acid (3-NP), a widely known toxin that selectively damages the striatum in the brain.

METHODSMouse model was made with subacute systemic 3-NP treatment, and the depressive-like behavior was measured using the duration of immobility during forced swimming test (FST).

RESULTSWhen the mice at day 15 post-intoxication just totally recovered from motor deficits, the duration of immobility in FST was significantly longer than that in controls. The depressive-like behavior was not due to the fatigue or general sickness following 3-NP intoxication and could be reversed by the antidepressant, desipramine hydrochloride. In two successive FST in 24 h interval, the depressive-like behavior could be observed again in subsequent FST (at day 16 post-intoxication), and the mice presented a normal "learned helplessness".

CONCLUSIONA novel depression animal model could be established in mice during the initial period of recovery from 3-NP intoxication. The depression-like behavior might occur independently without involvement of cognitive defects, and the striatal lesions may underlie the depression-like behavior attributable to 3-NP intoxication.

Animals ; Convulsants ; toxicity ; Corpus Striatum ; drug effects ; Depression ; chemically induced ; Disease Models, Animal ; Mice ; Motor Activity ; drug effects ; Nitro Compounds ; toxicity ; Propionates ; toxicity

This study is to offer a clinical pain-depression dyad therapy of ferulic acid, the pain-depression dyad induced by reserpine was established and the dose-effect relationship of ferulic acid on ameliorating pain-depression dyad was explored. Mice were randomly divided into control group, reserpine + vechile and reserpine + ferulic acid (5, 10, 20, 40 and 80 mg x kg(-1)) groups. The reserpine treated mice were tested with thermal hyperalgesia, mechanicial allodynia and forced swimming tests, and the SOD and NO levels of hippocampus and frontal cortex were measured. Moreover, the HPLC-ECD was used to detect the changes of central monoamines concentrations. Compared with control group, reserpine can induce a significant decrease in the nociceptive threshold and increase in the immobility time of the forced swimming test. The results suggested that reserpine significantly increased the level of nitrite in hippocampus and frontal cortex and reduced the levels of SOD, 5-HT and NE in these two brain regions. However, these indexes can be a dose-dependently reversed by ferulic acid (5, 10, 20, 40 and 80 mg x kg(-1)). Ferulic acid can reverse pain-depression dyad, especially at the dose of 80 mg x kg(-1). In addition, it can influence oxidative stress and monoamine level.
Animals ; Antidepressive Agents ; administration & dosage ; pharmacology ; Coumaric Acids ; administration & dosage ; pharmacology ; Depression ; chemically induced ; complications ; metabolism ; physiopathology ; Dopamine ; metabolism ; Dose-Response Relationship, Drug ; Frontal Lobe ; metabolism ; Hippocampus ; metabolism ; Hyperalgesia ; physiopathology ; Male ; Mice ; Mice, Inbred ICR ; Nitric Oxide ; metabolism ; Norepinephrine ; metabolism ; Pain ; chemically induced ; complications ; metabolism ; physiopathology ; Pain Measurement ; Random Allocation ; Reserpine ; adverse effects ; Serotonin ; metabolism ; Superoxide Dismutase ; metabolism ; Swimming ; physiology

OBJECTIVE: To investigate the role of hippocampal neurodevelopment in the antidepressant effect of baicalin. METHODS: Forty male Institute of Cancer Research mice were divided into control, corticosterone (CORT, 40 mg/kg), CORT+baicalin-L (25 mg/kg), CORT+baicalin-H (50 mg/kg), and CORT+fluoxetine (10 mg/kg) groups according to a random number table. An animal model of depression was established by chronic CORT exposure. Behavioral tests were used to assess the reliability of depression model and the antidepressant effect of baicalin. In addition, Nissl staining and immunofluorescence were used to evaluate the effect of baicalin on hippocampal neurodevelopment in mice. The protein and mRNA expression levels of neurodevelopment-related factors were detected by Western blot analysis and real-time polymerase chain reaction, respectively. RESULTS: Baicalin significantly ameliorated the depressive-like behavior of mice resulting from CORT exposure and promoted the development of dentate gyrus in hippocampus, thereby reversing the depressive-like pathological changes in hippocampal neurons caused by CORT neurotoxicity. Moreover, baicalin significantly decreased the protein and mRNA expression levels of glycogen synthase kinase 3β (GSK3β), and upregulated the expression levels of cell cycle protein D1, p-mammalian target of rapamycin (mTOR), doublecortin, and brain-derived neurotrophic factor (all P<0.01). There were no significant differences between baicalin and fluoxetine groups (P>0.05). CONCLUSION Baicalin can promote the development of hippocampal neurons via mTOR/GSK3β signaling pathway, thus protect mice against CORT-induced neurotoxicity and play an antidepressant role.
Male ; Animals ; Mice ; Corticosterone ; Fluoxetine/metabolism* ; Depression/chemically induced* ; Glycogen Synthase Kinase 3 beta/metabolism* ; Reproducibility of Results ; Antidepressive Agents/pharmacology* ; Hippocampus ; TOR Serine-Threonine Kinases/metabolism* ; RNA, Messenger/genetics* ; Behavior, Animal ; Disease Models, Animal ; Mammals/metabolism*

Synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD), is widely considered as one of the major mechanisms underlying learning and memory. This study explored hippocampal synaptic plasticity and spatial memory formation of an Alzheimer's disease (AD) rat model established by intrahippocampal injection of oligomeric Aβ(1-42). Twenty four Sprague-Dawley rats at 2.5 months of age were randomly divided into AD and control groups, and were bilaterally injected with 5 μg oligomeric Aβ(1-42) or normal saline into dentate gyrus (DG) of hippocampus. Morris water maze test was used to observe the capability of learning and memory of two groups, 30 d after injection. To investigate the variations of paired-pulse facilitation (PPF) and range of synaptic plasticity, field potentials were recorded in the DG of the dorsal hippocampus by stimulating the perforant path (PP). The results showed that oligomeric Aβ(1-42) obviously impaired spatial memory formation in rats (P < 0.05). Furthermore, oligomeric Aβ(1-42) reduced the PPF ratio (P < 0.05) and hippocampal LTP formation (P < 0.05), while facilitated the hippocampal LTD formation (P < 0.05). These data suggest that chronic Aβ aggregation impairs synaptic plasticity of hippocampal PP-DG pathway, which may be involved in the spatial memory deficit in AD rats.
Alzheimer Disease ; chemically induced ; physiopathology ; Amyloid beta-Peptides ; toxicity ; Animals ; Female ; Hippocampus ; physiopathology ; Long-Term Potentiation ; drug effects ; physiology ; Long-Term Synaptic Depression ; drug effects ; physiology ; Male ; Maze Learning ; Memory ; physiology ; Neuronal Plasticity ; drug effects ; physiology ; Oligopeptides ; toxicity ; Peptide Fragments ; toxicity ; Perforant Pathway ; physiology ; Rats ; Rats, Sprague-Dawley ; Synapses ; drug effects ; physiology

OBJECTIVETo investigate pharmacological effects of the total flavonoid in Hypericum perforatum on depression.

METHODExperimental depression was induced by subcutaneous injection of reserpine in mice. The concentration of monoamine transmitters including 5-HT and NE, the activity of monoamine oxidase (MAO) in brain and reserpine-induced symptoms of depression, such as ptosis, attenuation of autonomous activity, behavioral despair, acquired helplessness and sleep, were measured respectively to evaluate the effects of the total flavonoid in H. perforatum on the depression.

RESULTThe total flavonoid in H. perforatum significantly decreased the activity of MAO, inhibited the ptosis and the attenuation of autonomous behavior induced by reserpine respectively. The levels of 5-HT and NE were also attenuated by the total flavonoid in H. perforatum remarkably. In addition, the total flavonoid in H. perforatum was shown to inhibit behavioral despair and acquired helplessness and to prolong the sleep time in the mice. Following the treatment with the total flavonoid in H. perforatum, 5-THP, at the dosage without any side-effects, caused the tremble in the mice.

CONCLUSIONThe results indicate that total flavonoid in H. perforatum can significantly inhibit the depression.

Animals ; Antidepressive Agents ; pharmacology ; Brain ; metabolism ; Depression ; chemically induced ; enzymology ; physiopathology ; Female ; Flavonoids ; isolation & purification ; pharmacology ; Hypericum ; chemistry ; Male ; Mice ; Mice, Inbred ICR ; Monoamine Oxidase ; metabolism ; Motor Activity ; drug effects ; Norepinephrine ; metabolism ; Plants, Medicinal ; chemistry ; Reserpine ; Serotonin ; metabolism ; Sleep ; drug effects

OBJECTIVETo investigate the relationship between atopic allergy and depression and the role of DBP in the development of depression.

METHODSBALB/c mice were randomly divided into eight groups: saline; ovalbumin (OVA)-immunized; saline+DBP (0.45 mg/kg•d); saline+DBP (45 mg/kg•d); DBP (0.45 mg/kg•d) OVA-immunized; DBP (45 mg/kg•d) OVA-immunized; saline+hydrocortisone (30 mg/kg•d); and hydrocortisone (30 mg/kg•d)-exposed OVA-immunized. Behavior (e.g. open-field, tail suspension, and forced swimming tests), viscera coefficients (brain and spleen), oxidative damage [e.g. reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH)], as well as levels of IgE and IL-4, were then analyzed.

RESULTSIn the saline and OVA groups, the degree of depression symptoms in mice increased with increasing DBP concentration. Additionally, the OVA-immunity groups were associated with more serious depressive behavior compared with the same exposure concentration in the saline group. Oxidative damage was associated with a dose-dependent increase in DBP in the different groups. IL-4 and IgE levels were associated with low-dose DBP stimulation, which changed to high-dose inhibition with increasing DBP exposure, possibly due to spleen injury seen at high DBP concentrations.

CONCLUSIONDevelopment of an atopic allergy has the potential to increase the risk of depression in mice, and it seems that DBP helps OVA to exert its effect in our present model. Moreover, the results of our study implicate a certain connection between brain oxidative stress and depression, which deserves a further exploration.

Animals ; Behavior, Animal ; drug effects ; Body Weight ; Depression ; blood ; chemically induced ; immunology ; Dibutyl Phthalate ; immunology ; toxicity ; Environmental Pollutants ; immunology ; toxicity ; Hydrocortisone ; Hypersensitivity, Immediate ; blood ; complications ; Immunization ; Immunoglobulin E ; blood ; Interleukin-4 ; blood ; Male ; Mice ; Mice, Inbred BALB C ; Ovalbumin ; Oxidative Stress