Complex Effects of Sertraline and Citalopram on In Vitro Murine Breast Cancer Proliferation and on In Vivo Progression and Anxiety Level.

Some selective serotonin reuptake inhibitors (SSRIs), primarily sertraline, demonstrate anti-proliferative activity in malignant cell-lines and in xenografted mouse models of colorectal tumor. There is, however, a paucity of comparative studies on the anti-tumor effects of SSRIs. We compared the in vitro and in vivo effects of sertraline and citalopram on murine 4T1 breast cancer.

Long-term effects of intracranial islet grafting on cognitive functioning in a rat metabolic model of sporadic Alzheimer's disease-like dementia.

Accumulating evidence suggests that Alzheimer's disease is associated with brain insulin resistance, as are some other types of dementia. Intranasal insulin administration has been suggested as a potential approach to overcoming brain insulin resistance and improving cognitive functions. Islet transplantation into the cranial subarachnoid cavity was used as an alternative route for insulin delivery into the brain.

Intracranial Transplantation of Pancreatic Islets Attenuates Cognitive and Peripheral Metabolic Dysfunctions in a Rat Model of Sporadic Alzheimer's Disease.

Background: Alzheimer's disease (AD) is often associated with brain insulin resistance and peripheral metabolic dysfunctions. Recently, we developed a model of sporadic AD associated with obesity-related peripheral metabolic abnormalities in Lewis rats using intracerebroventricular administration of streptozotocin (icv-STZ).

Objective: We aimed to assess the effect of intracranially grafted pancreatic islets on cognitive and peripheral metabolic dysfunctions in the icv-STZ Lewis rats.

Intracerebroventricular Streptozotocin Induces Obesity and Dementia in Lewis Rats.

Background: Animal models of dementia associated with metabolic abnormalities play an important role in understanding the bidirectional relationships between these pathologies. Rodent strains develop cognitive dysfunctions without alteration of peripheral metabolism following intracerebroventricular administration of streptozotocin (icv-STZ).

Objective: We aimed to estimate the effect of icv-STZ on cognitive functions and peripheral metabolism in Lewis rats, which are rarely used for the induction of cognitive abnormalities.

BDNF overexpression prevents cognitive deficit elicited by adolescent cannabis exposure and host susceptibility interaction.

Cannabis abuse in adolescence is associated with increased risk of psychotic disorders. Δ-9-tetrahydrocannabinol (THC) is the primary psychoactive component of cannabis. Disrupted-In-Schizophrenia-1 (DISC1) protein is a driver for major mental illness by influencing neurodevelopmental processes.

Trans-generation enrichment of clozapine-responsiveness trait in mice using a subchronic hypo-glutamatergic model of schizophrenia:A preliminary study.

Background: Schizophrenia patients who do not respond to clozapine treatment represent the most debilitating type of schizophrenia with unmet needs for novel interventions. To date there is no validated animal model for clozapine-refractory schizophrenia.

Methods: We used poor performance in the social preference (SP) test of C57/BL mice exposed to subchronic phencyclidine (PCP) as a correlate of negative signs of schizophrenia.

Insulin delivery to the brain using intracranial implantation of alginate-encapsulated pancreatic islets.

There is increasing evidence supporting a link between cognitive dysfunctions and impaired brain insulin signalling. Insulin therapy has previously been tested as an approach to ameliorate brain insulin resistance and deficiency in patients with various brain disorders. However, current strategies for insulin delivery to the brain may induce severe hypoglycaemia when injected peripherally or show poor uptake when delivered intranasally.

Attenuated Weight Gain with the Novel Analog of Olanzapine Linked to Sarcosinyl Moiety (PGW5) Compared to Olanzapine.

Olanzapine-induced weight gain is associated with atherosclerosis, hypertension, dyslipidemia, and diabetes. We synthesized a novel antipsychotic drug (PGW5) possessing an olanzapine moiety linked to sarcosine, a glycine transporter 1 inhibitor. In this study, we compared the metabolic effects of PGW5 and olanzapine in a female rat model of weight gain.

Intracranial pancreatic islet transplantation increases islet hormone expression in the rat brain and attenuates behavioral dysfunctions induced by MK-801 (dizocilpine).

The treatment of rodents with non-competitive antagonist of the N-Methyl-D-aspartate (NMDA) receptor, MK-801 (dizocilpine), induces symptoms of psychosis, deficits in spatial memory and impairment of synaptic plasticity. Recent studies have suggested that insulin administration might attenuate the cognitive dysfunctions through the modulatory effect on the expression of NMDA receptors and on the brain insulin signaling. Intrahepatic pancreatic islet transplantation is known as an efficient tool for correcting impaired insulin signaling.

Effects of the anti-multiple sclerosis immunomodulator laquinimod on anxiety and depression in rodent behavioral models.

Laquinimod is a novel oral immunomodulatory drug for the treatment of multiple sclerosis (MS). Considering the frequent co-morbidity of MS with anxiety and depression, we sought to assess the antidepressant and anxiolytic effects of laquinimod in mouse models. Laquinimod (0.

A novel analog of olanzapine linked to sarcosinyl moiety (PGW5) demonstrates high efficacy and good safety profile in mouse models of schizophrenia.

Unlabelled: Schizophrenia is a chronic mental disorder related to hypo-functioning of glutamatergic neurotransmission. N-methyl-D-aspartate-receptor (NMDA-R) positive modulators were reported to reduce schizophrenia symptoms. However, their efficacy is low and inconsistent.

Dominant negative DISC1 mutant mice display specific social behaviour deficits and aberration in BDNF and cannabinoid receptor expression.

Unlabelled: OBJECTIVES. Disrupted in schizophrenia 1 (DISC1) is considered the most prominent candidate gene for schizophrenia. In this study, we aimed to characterize behavioural and brain biochemical traits in a mouse expressing a dominant negative DISC1mutant (DN-DISC1).

The effect of reboxetine co-administration with olanzapine on metabolic and endocrine profile in schizophrenia patients.

Rationale: We previously demonstrated that the addition of the selective norepinephrine reuptake inhibitor reboxetine attenuates olanzapine-induced weight gain. Using the same study sample, we also sought to determine whether reboxetine's weight-attenuating effect was accompanied by a beneficial effect on metabolic and endocrine parameters relevant to antipsychotic-induced weight gain and obesity.

Method: Blood samples at baseline and at the end of the 6-week trial were available for 54 participants who participated in previous double-blind, placebo-controlled studies of reboxetine (4 mg BID) addition to olanzapine-treated schizophrenia patients.

Neuroprotective and procognitive effects of sertraline: in vitro and in vivo studies.

Selective serotonin reuptake inhibitors (SSRIs) stimulate synaptic plasticity and neurogenesis, most likely via the MAP-kinase signal transduction pathway (by phosphorilation of ERK) and by stimulating neurotrophic factors such as brain derived neurotrophic factor (BDNF) and the neuroprotective protein (Bcl-2). Using human neuroblastoma cells (SHSY5Y), we found that sertraline and its derivative, desmethylsertraline, at low concentrations (1-10 μM), induced potent neurotrophic activity. Subsequently, we have treated for 21 days young and aged mice with sertraline.

Mesenchymal stem cells protect from sub-chronic phencyclidine insult in vivo and counteract changes in astrocyte gene expression in vitro.

Mesenchymal stem cells (MSCs) are an attractive cell source for regenerative medicine strategies in brain diseases. Experimental studies have shown that repeated administration of phencyclidine (PCP) leads to schizophrenia-like behavioral changes in mice. The aim of the present study was to explore the effectiveness of MSC transplantation into the hippocampus in attenuating PCP-induced social behavior deficits.

The effects of reboxetine treatment on depression-like behavior, brain neurotrophins, and ERK expression in rats exposed to chronic mild stress.

Chronic mild stress (CMS) in rats is an established rodent depression model. Antidepressants attenuate the depression-like symptoms and prevent the biochemical changes caused by stress. In the present study, we examined the effect of CMS and the selective norepinephrine reuptake inhibitor (NRI) reboxetine (REB) treatment on behavioral parameters in rats and on hippocampal and cortical neurotrophic factors.

Immunomodulatory effect of sertraline in a rat model of rheumatoid arthritis.

Objective: Previous studies suggest that selective serotonin reuptake inhibitors (SSRIs) modulate immune system functionality. SSRIs are the preferred treatment for major depressive disorder (MDD). A high rate of MDD is observed in rheumatoid arthritis (RA) patients.

The effects of fluoxetine treatment in a chronic mild stress rat model on depression-related behavior, brain neurotrophins and ERK expression.

Depression is associated with hippocampus (HC) volume loss. Chronic mild stress (CMS) in rats is a model of depression. Antidepressants attenuate HC volume loss and reverse the depression-like symptoms of stressed animals.

Intracerebral adult stem cells transplantation increases brain-derived neurotrophic factor levels and protects against phencyclidine-induced social deficit in mice.

Stem cell-based regenerative therapy is considered a promising cellular therapeutic approach for the patients with incurable brain diseases. Mesenchymal stem cells (MSCs) represent an attractive cell source for regenerative medicine strategies for the treatment of the diseased brain. Previous studies have shown that these cells improve behavioral deficits in animal models of neurological disorders such as Parkinson's and Huntington's diseases.

The immunomodulatory effect of the antidepressant sertraline in an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis.

Background: We have previously demonstrated the immunomodulatory activity of some selective serotonin reuptake inhibitors.

Objectives: In this research, we performed an in vivo/ex vivo study to evaluate the potential immunosuppressive effect of sertraline in an experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis.

Methods: Mice (C57/bl EAE) were treated with sertraline (5 mg/kg) or dexamethasone (1 mg/kg) 7 days after EAE induction and then 3 times weekly (for 3 weeks).

In vitro novel combinations of psychotropics and anti-cancer modalities in U87 human glioblastoma cells.

Glioblastoma multiforme (GBM) is a highly aggressive malignant brain tumor. Despite some recent improvement in the treatment of this malignancy, life expectancy of GBM patients remains extremely low. Therefore, continuous efforts to develop new treatment modalities are mandatory.

Proapoptotic and chemosensitizing effects of selective serotonin reuptake inhibitors on T cell lymphoma/leukemia (Jurkat) in vitro.

While selective serotonin reuptake inhibitors (SSRIs) are commonly used for psychiatric indications, evidence implies them to possess anti-cancerous properties as well. We evaluated such in vitro effects in malignant T cells (Jurkat), finding that exposure to high concentrations of sertraline (IC(50)=9.5 microM) or paroxetine (IC(50)=18 microM) yielded a considerable reduction in cellular viability, exceeding equimolar doses of the chemotherapeutics vincristine and cyclophosphamide (P<0.

Gamma-aminobutyric acid amides of nortriptyline and fluoxetine display improved pain suppressing activity.

The GABA amides of the antidepressants nortriptyline and fluoxetine, 1 and 2, were compared to their respective parent compounds in rodent models of pain. The amides significantly reduced early nociceptive and late inflammatory responses compared to nortriptyline or fluoxetine, where 1 exhibited overall better efficacy than 2. Amide 1 was most efficacious in lowering cytokine secretion, edema and hyperalgesia induced by formalin and lambda-carrageenan, respectively.