Atorvastatin ameliorates depressive behaviors via regulation of α7nAChR expression by PI3K/Akt-BDNF pathway in mice.

Some of the statins have been shown to have antidepressant effects, but whether atorvastatin (AV) has antidepressant effects is unknown. This study was to investigate the effect of AV treatment on depressive behaviors. Herein, we show that AV treatment had antidepressant-like effect in physiological conditions and antidepressant effect in depressive state which depended on α7 nicotinic acetylcholine receptor (α7nAChR) expression in the ventral hippocampus (vHPC), but not α4ß2 nicotinic acetylcholine receptor (α4ß2nAchR) expression in vHPC, nor the α7nAChR and α4ß2nAchR expression in dorsal hippocampus (dHPC). By using MLA, a selective α7nAChR antagonist, we investigated the role of α7nAChR in AV treatment. Behavior tests demonstrated that MLA abolished the antidepressant effect of AV. Besides, our data showed that AV treatment increased Akt phosphorylation, brain-derived neurotrophic factor (BDNF), synaptic related protein synapsin and spinophilin expression. The phosphatidylinositol-3 kinase (PI3K) inhibitor LY294002 reversed AV-induced increase of BDNF expression, newborn neurons and antidepressant behavior effects. Our study suggests that AV plays an antidepressant role by regulating synaptic plasticity of vHPC through PI3K/Akt-BDNF signaling pathway, which may be a good choice for depression treatment.

Lower regional gray matter volume in the absence of higher cortical amyloid burden in late-life depression.

Late-life depression (LLD) is associated with a risk of developing Alzheimer's disease (AD). However, the role of AD-pathophysiology in LLD, and its association with clinical symptoms and cognitive function are elusive. In this study, one hundred subjects underwent amyloid positron emission tomography (PET) imaging with [18F]-flutemetamol and structural MRI: 48 severely depressed elderly subjects (age 74.1 ± 7.5 years, 33 female) and 52 age-/gender-matched healthy controls (72.4 ± 6.4 years, 37 female). The Geriatric Depression Scale (GDS) and Rey Auditory Verbal Learning Test (RAVLT) were used to assess the severity of depressive symptoms and episodic memory function respectively. Amyloid deposition was quantified using the standardized uptake value ratio. Whole-brain voxel-wise comparisons of amyloid deposition and gray matter volume (GMV) between LLD and controls were performed. Multivariate analysis of covariance was conducted to investigate the association of regional differences in amyloid deposition and GMV with clinical factors, including GDS and RAVLT. As a result, there were no significant group differences in amyloid deposition. In contrast, LLD showed significant lower GMV in the left temporal and parietal region. GMV reduction in the left temporal region was associated with episodic memory dysfunction, but not with depression severity. Regional GMV reduction was not associated with amyloid deposition. LLD is associated with lower GMV in regions that overlap with AD-pathophysiology, and which are associated with episodic memory function. The lack of corresponding associations with amyloid suggests that lower GMV driven by non-amyloid pathology may play a central role in the neurobiology of LLD presenting as a psychiatric disorder.Trial registration: European Union Drug Regulating Authorities Clinical Trials identifier: EudraCT 2009-018064-95.

Xanthohumol Attenuates Lipopolysaccharide-Induced Depressive Like Behavior in Mice: Involvement of NF-κB/Nrf2 Signaling Pathways.

Depression is the most common psychiatric disorder associated with brain and immune system abnormalities. In recent years, xanthohumol (Xn) a bioactive prenylated flavonoid has received ample attention for its polypharmacological effects, therefore, here we aimed to explore the protective effects of Xn against the LPS-induced depressive-like symptoms mediated by inflammation and oxidative stress. We tested the effect of Xn against LPS-induced behavioural changes in mice by means of forced swimming test (FST), tail suspention test (TST), sucrose preference test (SPT) and open field test (OPT). Examined the neuroinflammation and oxido-nitrosative stress (O&NS) markers and analyze Nrf2 and NF-κB signalling pathways in the hippocampus. Our results indicated that peripheral repeated administration of lipopolysaccharides (LPS) (1 mg/kg, intra peritoneally) induced depressive-like behavior, neuroinflammation and O&NS in mice. Pretreatment with Xn (10 and 20 mg/kg, intra gastrically) reverse the behavioural impairments prophylactically as obvious in the FST and TST without effecting locomotion, however only 20 mg dose improve anhedonic behavior as observed in SPT. Similarly, Xn pretreatment in dose-dependent manner prevented the LPS induced neuro-inflammation and O&NS. Immunofluorescence analysis showed that Xn reduced activated gliosis via attenuation of Iba-1 and GFAP in hippocampus. In addition, Xn considerably reduced the expression of phospho-NF-κB and cleaved caspase-3 while enhanced Nrf2 and HO-1 expression in the hippocampus. To the best of our knowledge, this is the first study to examine the underlying beneficial prophylactic effects of the Xn in neuroinflammation and O&NS mediating depressive-like behaviors.

Exogenous Hydrogen Sulfide Plays an Important Role by Regulating Autophagy in Diabetic-Related Diseases.

Autophagy is a vital cell mechanism which plays an important role in many physiological processes including clearing long-lived, accumulated and misfolded proteins, removing damaged organelles and regulating growth and aging. Autophagy also participates in a variety of biological functions, such as development, cell differentiation, resistance to pathogens and nutritional hunger. Recently, autophagy has been reported to be involved in diabetes, but the mechanism is not fully understood. Hydrogen sulfide (H2S) is a colorless, water-soluble, flammable gas with the typical odor of rotten eggs, which has been known as a highly toxic gas for many years. However, it has been reported recently that H2S, together with nitric oxide and carbon monoxide, is an important gas signal transduction molecule. H2S has been reported to play a protective role in many diabetes-related diseases, but the mechanism is not fully clear. Recent studies indicate that H2S plays an important role by regulating autophagy in many diseases including cancer, tissue fibrosis diseases and glycometabolic diseases; however, the related mechanism has not been fully studied. In this review, we summarize recent research on the role of H2S in regulating autophagy in diabetic-related diseases to provide references for future related research.

Mood alterations in mouse models of Spinocerebellar Ataxia type 1.

Spinocerebellar ataxia type 1 (SCA1) is a fatal neurodegenerative disease caused by abnormal expansion of glutamine-encoding CAG repeats in the Ataxin-1 (ATXN1) gene. SCA1 is characterized by progressive motor deficits, cognitive decline, and mood changes including anxiety and depression, with longer number of repeats correlating with worse disease outcomes. While mouse models have been very useful in understanding etiology of ataxia and cognitive decline, our understanding of mood symptoms in SCA1 has lagged. It remains unclear whether anxiety or depression stem from an underlying brain pathology or as a consequence of living with an untreatable and lethal disease. To increase our understanding of the etiology of SCA1 mood alterations, we used the elevated-plus maze, sucrose preference and forced swim tests to assess mood in four different mouse lines. We found that SCA1 knock-in mice exhibit increased anxiety that correlated with the length of CAG repeats, supporting the idea that underlying brain pathology contributes to SCA1-like anxiety. Additionally, our results support the concept that increased anxiety is caused by non-cerebellar pathology, as Purkinje cell specific SCA1 transgenic mice exhibit decreased anxiety-like behavior. Regarding the molecular mechanism, partial loss of ATXN1 may play a role in anxiety, based on our results for Atxn1 haploinsufficient and null mice.

Depression and Impulsivity Self-Assessment Tools to Identify Dopamine Agonist Side Effects in Patients With Pituitary Adenomas.

Background: Dopamine agonists (DA) are the first line therapy for prolactinoma and symptomatic hyperprolactinemia; use as an adjuvant treatment for acromegaly and Cushing's disease is rare. Some patients develop de novo psychiatric symptoms or have exacerbation of pre-existing conditions during DA therapy. A practical, clinically sensitive depression and impulse control disorders (ICD; particularly hypersexuality and gambling disorders) detection tool is important for identifying at risk patients. The Barratt Impulsivity Scale (BIS-11) and the 9-item Patient Health Questionnaire (PHQ-9) are sensitive in identifying impulsivity and depression. Objective: Detail use of the BIS-11 and PHQ-9 as screening tools for depression and ICD in patients with pituitary disease at a high-volume academic pituitary center. Methods: DA-treated and naïve patients with pituitary disease were included. Patients with a known history of depression or psychiatric disorder were excluded. PHQ-9 standardized interpretation criteria were utilized to classify depression severity. For BIS-11, threshold was established based on previous studies. Statistical analysis was with SPSS version 25. Results: Seventy-six DA-treated and 27 naïve patients were included. Moderate and moderately severe depression were more prevalent in DA-treated patients; severe depression only found in DA-treated patients. A normal BIS-11 score was noted in 76.69%; higher scores (not significant) were noted in DA-treated patients. There was a positive correlation between higher BIS-11 and PHQ-9 scores; higher in DA-treated patients (r = 0.52, p < 0.001) than DA-naïve patients. Patients with BIS-11 scores ≥60 were younger and received lower cumulative DA doses compared to patients with BIS scores <60. There was no association between male sex and BIS-11 ≥60 and male sex did not increase the odds of increased scores (OR = 0.66, CI95% 0.25-1.76, p = 0.41). No significant difference was found for macroadenoma, prolactin levels, testosterone levels, hypogonadism, testosterone replacement in men, and increased impulsivity or depression scores. Conclusion: Use of PHQ-9 and BIS-11 is practical for routine screening of depression and ICD during outpatient pituitary clinic visits for patients with pituitary disease both naïve to treatment and during DA therapy. We recommend close follow-up after initiation of DA therapy for younger patients, regardless of dose.

Transient effects of chemotherapy for testicular cancer on mouse behaviour.

The treatment of testicular cancer includes unilateral orchiectomy and chemotherapy and is curative for most patients. However, observational studies revealed an association with depression, anxiety and cognitive impairment. It is unclear whether these side effects are caused by chemotherapy, hemicastration or the disease itself. The aim of our study was to analyse the behavioural effects of hemicastration and chemotherapy in adult male mice. The animals were randomly divided into four groups - control, chemotherapy, hemicastration and hemicastration with chemotherapy. After chemotherapy that included three cycles of bleomycin, etoposide, cisplatin mice underwent a battery of behavioural tests. To assess the long-term effects animals were tested also 3 months after the end of treatment. Chemotherapy led to lower locomotor- and exploratory activity, higher anxiety-like behaviour and worse spatial memory immediately after treatment. These behavioural effects were not present three months later. Hemicastration had no effect on most of the observed outcomes. In conclusion, adverse behavioural effects induced by chemotherapy in mice are transient and disappear later in life. Further studies are needed to elucidate the mechanisms responsible for the observed effects.

The association of depressive symptoms, personality traits, and sociodemographic factors with health-related quality of life and quality of life in patients with advanced-stage lung cancer: an observational multi-center cohort study.

BACKGROUND: Identification of patient-related factors associated with Health-Related Quality of Life (HRQoL) and Quality of Life (QoL) at the start of treatment may identify patients who are prone to a decrease in HRQoL and/or QoL resulting from chemotherapy. Identification of these factors may offer opportunities to enhance patient care during treatment by adapting communication strategies and directing medical and psychological interventions. The aim was to examine the association of sociodemographic factors, personality traits, and depressive symptoms with HRQoL and QoL in patients with advanced-stage lung cancer at the start of chemotherapy. METHODS: Patients (n = 151) completed the State-Trait Anxiety Inventory (trait anxiety subscale), the Neuroticism-Extraversion-Openness-Five Factor Inventory (NEO-FFI), the Center for Epidemiologic Studies Depression (CES-D), the World Health Organization Quality of Life-BREF (WHOQOL-BREF), and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). Simple linear regression analyses were performed to select HRQoL and QoL associated factors (a P ≤ 0.10 was used to prevent non-identification of important factors) followed by multiple linear regression analyses (P ≤ 0.05). RESULTS: In the multiple regression analyses, CES-D score (ß = - 0.63 to - 0.53; P-values < 0.001) was most often associated with the WHOQOL-BREF domains and general facet, whereas CES-D score (ß = - 0.67 to - 0.40; P-values < 0.001) and Eastern Cooperative Oncology Group (ECOG) performance status (ß = - 0.30 to - 0.30; P-values < 0.001) were most often associated with the scales of the EORTC QLQ-C30. Personality traits were not related with HRQoL or QoL except for trait anxiety (Role functioning: ß = 0.30; P = 0.02, Environment: ß = - 0.39; P = 0.007) and conscientiousness (Physical health: ß = 0.20; P-value < 0.04). CONCLUSIONS: Higher scores on depressive symptoms and ECOG performance status were related to lower HRQoL and QoL in patients with advanced-stage non-small cell lung cancer. Supportive care interventions aimed at improvement of depressive symptoms and performance score may facilitate an increase of HRQoL and/or QoL during treatment.

Treatment-induced symptoms, depression and age as predictors of sexual problems in premenopausal women with early breast cancer receiving adjuvant endocrine therapy.

PURPOSE: Sexual dysfunction is an important concern of premenopausal women with early breast cancer. We investigated predictors of sexual problems in two randomized controlled trials. METHODS: A subset of patients enrolled in TEXT and SOFT completed global and symptom-specific quality-of-life indicators, CES-Depression and MOS-Sexual Problems measures at baseline, six, 12 and 24 months. Mixed models tested the association of changes in treatment-induced symptoms (baseline to 6 months), depression at 6 months, and age at randomization with changes in sexual problems over 2 years. RESULTS: Sexual problems increased by 6 months and persisted at this level. Overall, patients with more severe worsening of vaginal dryness, sleep disturbances and bone or joint pain at 6 months reported a greater increase in sexual problems at all time-points. Depression scores were significantly associated with sexual problems in the short-term. All other symptoms had a smaller impact on sexual problems. Age was not associated with sexual problems at any time-point. CONCLUSION: Among several key symptoms, vaginal dryness, sleep disturbance, and bone and joint pain significantly predicted sexual problems during the first 2 years. Early identification of these symptoms may contribute to timely and tailored interventions.

A comparison study of metabolic profiles, immunity, and brain gray matter volumes between patients with bipolar disorder and depressive disorder.

BACKGROUND: Previous individual studies have shown the differences in inflammatory cytokines and gray matter volumes between bipolar disorder (BD) and unipolar depression (UD). However, few studies have investigated the association between pro-inflammatory cytokines and differences in brain gray matter volumes between BD and UD. METHODS: In this study, 72 BD patients and 64 UD patients were enrolled, with comparable gender and age distributions (33.8% males and an average age of 39.3 ± 13.7 years). Each participant underwent metabolic profiling (including body mass index (BMI), glucose, triglyceride, high-density lipoprotein (HDL), leptin, insulin, adiponectin), pro-inflammatory cytokine (including soluble interleukin-6 receptor (sIL-6R), soluble interleukin-2 receptor (sIL-2R), C-reactive protein (CRP), soluble tumor necrosis factor receptor type 1 (sTNF-R1) examinations, and structural magnetic resonance imaging exams. Voxel-based morphometry was performed to investigate the gray matter volume differences between BD and UD patients. Correlations between pro-inflammatory cytokines and the gray matter volume difference were analyzed. RESULTS: Compared to UD patients, the BD group had significantly higher BMI, and higher levels of sIL-6R and sTNF-R1 than the UD patients. The BMI significantly correlated with the level of pro-inflammatory cytokines. Adjusted for age, sex, BMI, duration of illness and total intracranial volume, the BD individuals had significantly more reduced gray matter volumes over 12 areas: R. cerebellar lobule VIII, R. putamen, L. putamen, R. superior frontal gyrus, L. lingual gyrus, L. precentral gyrus, R. fusiform gyrus, L. calcarine, R. precuneus, L. inferior temporal gyrus, L. hippocampus, and L. superior frontal gyrus. These 12 gray matter volume differences between BP and UD patients negatively correlated with sIL-6R and sTNF-R1 levels. CONCLUSIONS: Our results suggested that BD patients had higher BMI and pro-inflammatory cytokine levels in comparison to UD patients, especially IL-6 and sTNF-R1, which may contribute to greater gray matter reductions in BD patients in comparison to UD patients. The results support the neuro-inflammation pathophysiology mechanism in mood disorder. It is clinically important to monitor BMI, which, in this investigation, positively correlated with levels of inflammatory cytokines.

Proteomics-based screening of the target proteins associated with antidepressant-like effect and mechanism of Saikosaponin A.

Depression is a commonly occurring neuropsychiatric disease with an increasing incidence rate. Saikosaponin A (SA), a major bioactive component extracted from Radix Bupleuri, possesses anti-malignant cell proliferation, anti-inflammation, anti-oxidation and liver protective effects. However, few studies have investigated SA's antidepressant effects and pharmacological mechanisms of action. Our study aimed to explore the anti-depression effect of SA and screen the target proteins regulated by SA in a rat model of chronic unpredictable mild stress (CUMS)-induced depression. Results showed that 8-week CUMS combined with separation could successfully produce depressive-like behaviours and cause a decrease of dopamine (DA) in rat hippocampus, and 4-week administration of SA could relieve CUMS rats' depressive symptoms and up-regulated DA content. There were 15 kinds of significant differentially expressed proteins that were detected not only between the control and CUMS groups, but also between the CUMS and SA treatment groups. Proline-rich transmembrane protein 2 (PRRT2) was down-regulated by CUMS while up-regulated by SA. These findings reveal that SA may exert antidepressant effects by up-regulating the expression level of PRRT2 and increasing DA content in hippocampus. The identification of these 15 differentially expressed proteins, including PRRT2, provides further insight into the treatment mechanism of SA for depression.

Therapeutic Potential of Hericium erinaceus for Depressive Disorder.

Depression is a common and severe neuropsychiatric disorder that is one of the leading causes of global disease burden. Although various anti-depressants are currently available, their efficacies are barely adequate and many have side effects. Hericium erinaceus, also known as Lion's mane mushroom, has been shown to have various health benefits, including antioxidative, antidiabetic, anticancer, anti-inflammatory, antimicrobial, antihyperglycemic, and hypolipidemic effects. It has been used to treat cognitive impairment, Parkinson's disease, and Alzheimer's disease. Bioactive compounds extracted from the mycelia and fruiting bodies of H. erinaceus have been found to promote the expression of neurotrophic factors that are associated with cell proliferation such as nerve growth factors. Although antidepressant effects of H. erinaceus have not been validated and compared to the conventional antidepressants, based on the neurotrophic and neurogenic pathophysiology of depression, H. erinaceus may be a potential alternative medicine for the treatment of depression. This article critically reviews the current literature on the potential benefits of H. erinaceus as a treatment for depressive disorder as well as its mechanisms underlying the antidepressant-like activities.

Assessing the role of toll-like receptor in isolated, standard and enriched housing conditions.

Depression is a common psychiatric disorder that has been poorly understood. Consequently, current antidepressant agents have clinical limitations. Until today, most have exhibited the slow onset of therapeutic action and, more importantly, their effect on remission has been minimal. Thus, the need to find new forms of therapeutic intervention is urgent. The inflammation hypothesis of depression is widely acknowledged and is one that theories the relationship between the function of the immune system and its contribution to the neurobiology of depression. In this research, we utilized an environmental isolation (EI) approach as a valid animal model of depression, employing biochemical, molecular, and behavioral studies. The aim was to investigate the anti-inflammatory effect of etanercept, a tumor necrosis factor-α inhibitor on a toll-like receptor 7 (TLR 7) signaling pathway in a depressive rat model, and compare these actions to fluoxetine, a standard antidepressant agent. The behavioral analysis indicates that depression-related symptoms are reduced after acute administration of fluoxetine and, to a lesser extent, etanercept, and are prevented by enriched environment (EE) housing conditions. Experimental studies were conducted by evaluating immobility time in the force swim test and pleasant feeling in the sucrose preference test. The mRNA expression of the TLR 7 pathway in the hippocampus showed that TLR 7, MYD88, and TRAF6 were elevated in isolated rats compared to the standard group, and that acute treatment with an antidepressant and anti-inflammatory drugs reversed these effects. This research indicates that stressful events have an impact on behavioral well-being, TLR7 gene expression, and the TLR7 pathway. We also found that peripheral administration of etanercept reduces depressive-like behaviour in isolated rats: this could be due to the indirect modulation of the TLR7 pathway and other TLRs in the brain. Furthermore, fluoxetine treatment reversed depressive-like behaviour and molecularly modulated the expression of TLR7, suggesting that fluoxetine exerts antidepressant effects partially by modulating the TLR7 signaling pathway.

Anxiety and depression relationship with coronary slow flow.

BACKGROUND: Psychiatric disorders (depression / anxiety) are linked to coronary artery disease (CAD). Coronary slow flow (CSF) is a relatively common form of CAD with the same underlying mechanisms that are attributed to many anatomic and pathophysiologic factors. However, the relationship between psychiatric disorders and CSF is less well-established; and this is the aim of this study. METHODS: This cross-sectional observational study was conducted on the first 50 consecutive patients diagnosed with CSF by elective coronary angiography (CAG). They were compared with another 50 consecutive patients showing normal coronaries by CAG. Beck Anxiety Inventory and Beck Depression Inventory were used for assessment. CSF was diagnosed by coronary angiography "Thrombolysis In Myocardial Infarction" frame count. Lipid profile was obtained for all patients. RESULTS: Traditional risk factors (male gender, smoking, total cholesterol, low-density lipoproteins and triglycerides) were higher in the CSF group. Depression and anxiety scores were also higher in the CSF group. On multivariate analysis, male gender, depression and high triglycerides were the only significant independent predictors of CSF. A significant correlation existed between CSF and both anxiety and depression scores. Both scores were also significantly higher in multivessel vs single vessel affection. CONCLUSION: Psychiatric depression, male gender and high triglycerides are highly associated with CSF in patients undergoing elective CAG. There is a significant correlation between CSF severity and the severity of both anxiety and depression. Further studies are warranted to explore the impact of psychological intervention on CSF and its long-term outcome.

Risk of Developing Hepatocellular Carcinoma following Depressive Disorder Based on the Expression Level of Oatp2a1 and Oatp2b1.

BACKGROUND: Accumulating evidence from prospective epidemiological studies has showed that depression disorder (DD) is a risk factor for cancer. The aim of this study is to explore the association of DD and the overall occurrence risk of hepatocellular carcinoma (HCC) and the mechanism. METHODS: In this study, 60 mice were randomly divided into four groups: Control group, DD group, HCC group, HCC-DD group. Mice received a chronic dose of reserpine to establish depression model, followed by Diethylnitrosamine and Carbon tetrachloride administration to establish HCC models. Behavioral depression was assessed by sucrose preference test (SPT) and the expression of Serotonin 1A (5-HT1A) receptor in the hippocampal. The expression of Oatp2a1 and Oatp2b1 in the digestive system tissues was detected by PCR and western blotting. RESULTS: Reserpine-administrated mice had a reducing sucrose preference at Day 14 compared with blank mice (P<0.05). The expression of 5-HT1A receptor in the hippocampal was decreased in DD mice compared with blank mice. The survival analysis indicated that the HCC mice with DD have poorer survival rate compared with the HCC mice. Compared with HCC mice, the expression of Oatp2a1 and Oatp2b1 was lower in liver and stomach tissue and higher in hepatic carcinoma and colon tissue of HCC-DD mice (P<0.05), and the expression of Oatp2a1 was higher in the spleen tissue of HCC-DD mice while the expression of Oatp2b1 was lower (P<0.05). However, no difference was found in the expression of Oatp2a1 and Oatp2b1 in the small intestine tissue between HCC group and HCC-DD group. CONCLUSIONS: DD was the adverse factors for the overall occurrence risk of HCC. Mechanistically, be the downregulation of Oatp2a1 and Oatp2b1 in liver tissue induced by DD might be involved.

Los síntomas melancólicos del filósofo en las Intercenales (1424-1439) de Leon Battista Alberti / The melancholy of the philosopher in the Intercenales (1424-1439)

This essay analyzes the presence of the modern concept of melancholy in the Intercenales (1424-1439) by the humanist Leon Battista Alberti. The Intercenales is a collection of satirical, allegorical and moralizing writings composed with the purpose of entertaining an audience of close friends. In spite of the fact that the term "melancholia" does not appear in the text, this paper argues that Alberti's character of "the philosopher" is melancholic, since he is "ill in the soul" (suffering from morbus animi), and his illness is evidenced by a series of physical and psychological symptoms associated with melancholy in the classical and medieval medical traditions. These symptoms are stomach pain, pallor, insomnia, a rich memory, a propensity to study at night, and an ability to have premonitory dreams. With this characterization Alberti promotes a connection between melancholy and being a genius, which is distinctive to the Renaissance and the basis for the modern concept of melancholy. The essay concludes that the ultimate purpose of the Intercenales is to cure, from a literary and philosophical point of view, the illness of the melancholic philosopher.

Bax inhibitor-1 overexpression in prelimbic cortex protects rats against depression-like behavior induced by olfactory bulbectomy and reduces apoptotic and inflammatory signals.

BACKGROUND AND PURPOSE: Depression is a mental disorder characterized by a pervasive low mood and loss of pleasure or interest in usual activities, and often results in the impairment of learning and memory. Bax inhibitor-1 (BI-1) has been reported to be involved in the pathological mechanisms for neurodegenerative disorders including depression. Here, we aimed to investigate the role of BI-1 in regulating depression-like behavior induced by olfactory bulbectomy (OB) in rats and the possible mechanism. METHODS: Adeno-associated virus vectors expressing BI-1 (AAV-BI-1) were bilaterally microinjected into the prelimbic cortex (PFC-PL) to establish a BI-1 overexpression model in the PFC-PL of rats. TUNEL staining was used to evaluate the cellular apoptosis rate in the PFC-PL. Western blot analysis was performed to examine the expressions of apoptotic and inflammatory signals. RESULTS: BI-1 overexpression significantly attenuated the OB-induced behavioral abnormalities, including the decreased hyperactivity in the open field, decreased immobility time in the forced swimming test, as well as the increased sucrose consumption. BI-1 overexpression significantly inhibited cellular apoptosis in the PFC-PL of OB rats. The expressions of tumor necrosis factor (TNF)-α, interleukin (IL)-6, B-cell lymphoma (Bcl)-2 associated X protein (Bax), and caspase-3 in the PFC-PL of OB rats were significantly increased as compared with the sham rats, but the Bcl-2 and IL-10 expressions were decreased, whereas BI-1 overexpression significantly suppressed the changes of these proteins in the PFC-PL of OB rats. CONCLUSION: These results indicated that BI-1 may play an anti-depression function with concurrent regulation of apoptotic and inflammatory signals.

Olfactory bulbus volume and olfactory sulcus depth in psychotic patients and patients with anxiety disorder/depression.

OBJECTIVES: In the present study, we investigated olfactory bulb (OB) volume and olfactory sulcus (OS) depth of the psychotic patients (predominantly schizophrenia) and patients with anxiety disorder/depression. METHODS: This study was conducted retrospectively. Group 1 consisted of 30 psychotic patients (predominantly schizophrenia) (19 males and 11 females). Group 2 consisted of 37 patients with anxiety disorder/depression (10 males, 27 females). Group 3 consisted of 30 non-psychotic and non-anxiety disorder/depression subjects (9 males and 21 females). OB volume and OS depth measurements were performed on Cranial MRI. RESULTS: OB volume (right and left) of the psychotic; and anxiety disorder/depression groups were significantly lower than those of the control group (padjusted < 0.0175). OS depth (Left) value of anxiety disorder/depression group was significantly lower than those of the control group (padjusted < 0.0175). In psychotic and anxiety disorder/depression groups, left OS depth values were significantly lower than those of the right side (p < 0.05). In each of the males and females of the anxiety disorder/depression group, left OS depth values were significantly lower than those of the right side (p < 0.05). In psychotic group, OS depth (left) values get lower in older patients (p < 0.05). CONCLUSION: Decreased OB volume in the psychotic patients and decreased OB volume and OS depth in anxiety disorder/depression patients were detected. Lower OB volume and OS depth are related to the olfactory loss/or olfactory impairment. Physicians should be aware of the olfactory deficits in psychotic patients (mainly schizophrenia) and patients with anxiety disorder/depression. When reduced OB volume is detected on MRI, psychosis, schizophrenia or depression should also be kept in mind and the patients should be evaluated in detail for these diseases.

Mechanisms underlying the rapid-acting antidepressant-like effects of neuropeptide VGF (non-acronymic) C-terminal peptide TLQP-62.

Previous studies have revealed that neuropeptide VGF (non-acronymic) C-terminal peptide TLQP-62 rapidly activates brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB)/α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor/mammalian target of rapamycin (mTOR) signaling and produces antidepressant-like actions in rodents. In addition, acute TLQP-62 infusion also markedly changes the AMPA receptor GluA1 subunit phosphorylation at Ser 845 (pGluA1 Ser845) in the PFC of mice, indicating that the GluA1 may contributes to the rapid antidepressant-like effects of TLQP-62. However, how to regulate the TrkB-mediated signaling and GluA1 changes in the prefrontal cortex (PFC) by TLQP-62 remains unclear. Herein, acute administration of TLQP-62 into PFC produced rapid-acting antidepressant-like effects in mice. Additionally, we confirmed that TLQP-62 ameliorated the depression-like behaviors induced by chronic social defeat stress (CSDS) in mice. Further investigation demonstrated that this effect of TLQP-62 was mediated by activation of TrkB and mTOR, which proceeded to decrease bicaudal C homolog 1 gene (BICC1) and increase synaptic protein expression, including GluA1 subunit and pGluA1 Ser845. Notably, we further found that beneficial effects of TLQP-62 on depression-like behaviors and TrkB/mTOR/BICC1 signaling, GluA1 phosphorylation and GluA1 activation in the PFC of mice were significantly abolished by TrkB antagonist ANA-12. In conclusion, our findings indicate that TrkB/mTOR/BICC1 signaling, GluA1 phosphorylation and GluA1 activation in the PFC may involve in the rapid-acting antidepressant-like actions of TLQP-62 in mice.

HTLV-1 infection-induced motor dysfunction, memory impairment, depression, and brain tissues oxidative damage in female BALB/c mice.

AIMS: The HTLV-1 infection is associated with a neuro-inflammatory disease. In the present study, the behavioral consequences and brain oxidative damages were evaluated in HTLV-1-infected BALB/c mice. MATERIAL AND METHODS: 20 female BALB/c mice were divided into two groups comprising control and HTLV-1-infected. The HTLV-1-infected group was inoculated with a 106 MT-2 HTLV-1-infected cell line. Two months later, the behavioral tests were conducted. Finally, oxidative stress was assessed in the cortex and hippocampus tissues. KEY FINDINGS: In the HTLV-1-infected group, running time and latency to fall, travel distance and time spent in the peripheral zone, total crossing number and total traveled distance in open field test, the latency of entrance into the dark compartment in the passive avoidance test, the new object exploration percentage, and discrimination ratio were significantly lower than in the control group. The immobility time, time spent in the dark compartment in passive avoidance test, and total exploration time significantly increased in the HTLV-1-infected group compared to the control group. In the cortical tissue of the HTLV-1 group, the malondialdehyde levels were elevated while the total thiol levels decreased in comparison to the control group. The activity of superoxide dismutase in the cortical and hippocampal tissues, and catalase activity in cortical tissue significantly decreased in the HTLV-1 group in comparison to the control group. SIGNIFICANCE: The HTLV-1 infection seems to induce depression-like behavior, motor dysfunction, disruption in working and fear memory and also oxidative stress in the cortex and hippocampus.