Ethopharmacological evaluation of antidepressant-like effect of serotonergic psychedelics in C57BL/6J male mice.

Serotonergic psychedelics such as psilocybin, lysergic acid diethylamide, and DOI exert a hallucinatory effect through serotonin 5-HT receptor (5-HT2A) activation. Recent studies have revealed that serotonergic psychedelics have therapeutic potential for neuropsychiatric disorders, including major depressive and anxiety-related disorders. However, the involvement of 5-HT2A in mediating the therapeutic effects of these drugs remains unclear.

Emotional behaviors as well as the hippocampal reelin expression in C57BL/6N male mice chronically treated with corticosterone.

Depression is a common psychiatric disorder affecting around 300 million people worldwide. Serum cortisol and glucocorticoid levels in humans are reportedly higher in patients with depression compared to controls. Furthermore, rodents repeatedly treated with exogenous corticosterone (CORT), a glucocorticoid in rodents, exhibit deficits in emotional behaviors.

Ethopharmacological evaluation of antidepressant-like effect of serotonergic psychedelics in C57BL/6J male mice.

Serotonergic psychedelics such as psilocybin, lysergic acid diethylamide, and DOI exert a hallucinatory effect through serotonin 5-HT 2A receptor (5-HT2A) activation. Recent studies have revealed that serotonergic psychedelics have therapeutic potential for neuropsychiatric disorders, including major depressive and anxiety-related disorders. However, the involvement of 5-HT2A in mediating the therapeutic effects of these drugs remains unclear.

Role of sirtuin1 in impairments of emotion-related behaviors in mice with chronic mild unpredictable stress during adolescence.

Long-term exposure to physical and/or psychosocial stress during early life and/or adolescence increases the risk of psychiatric disorders such as major depressive disorder and anxiety disorders. However, the molecular mechanisms underlying early stress-induced brain dysfunction are poorly understood. In the present study, mice at 4 weeks old were subjected to chronic mild unpredictable stress (CMUS) for 4 weeks, and subsequently to assays of emotion-related behaviors.

Preventive Effect of Betaine Against Cognitive Impairments in Amyloid β Peptide-Injected Mice Through Sirtuin1 in Hippocampus.

In the pathophysiology of Alzheimer's disease, the deposition of amyloid β peptide (Aβ) is associated with oxidative stress, leading to cognitive impairment and neurodegeneration. We have already reported that betaine (glycine betaine), an osmolyte and methyl donor in cells, prevents the development of cognitive impairment in mice with intracerebroventricular injection of Aβ, an active fragment of Aβ, associated with oxidative stress in the hippocampus, but molecular mechanisms of betaine remain to be determined. Here, to investigate a key molecule underlying the preventive effect of betaine against cognitive impairments in Aβ-injected mice, cognitive tests and qPCR assays were performed in Aβ-injected mice with continuous betaine intake, in which intake was started a day before Aβ injection, and then continued for 8 days.

Effects of galantamine on social interaction impairments in cholecystokinin receptor-2 overexpression mice.

We examined whether galantamine (GAL), a cholinesterase inhibitor and allosteric potentiating ligand for α7 nicotinic acetylcholine receptor (nAChR), had an impact on emotional abnormalities in forebrain-specific cholecystokinin receptor-2 overexpressed transgenic mice. Treatment with GAL (1 mg/kg, s.c.

Preventive Effects of Continuous Betaine Intake on Cognitive Impairment and Aberrant Gene Expression in Hippocampus of 3xTg Mouse Model of Alzheimer's Disease.

Background: The deposition of amyloid-β (Aβ) and hyperphosphorylation of tau are well-known as the pathophysiological features of Alzheimer's disease (AD), leading to oxidative stress and synaptic deficits followed by cognitive symptoms. We already demonstrated that betaine (glycine betaine) prevented cognitive impairment and hippocampal oxidative stress in mice intracerebroventricularly injected with an active fragment of Aβ, whereas the effect of betaine in chronic models of AD remains unknown.

Objective: Our objective was to investigate the effects of chronic betaine intake on cognitive impairment and aberrant expression of genes involved in synapse and antioxidant activity in the hippocampus of a genetic AD model.

Reelin Supplementation Into the Hippocampus Rescues Abnormal Behavior in a Mouse Model of Neurodevelopmental Disorders.

In the majority of schizophrenia patients, chronic atypical antipsychotic administration produces a significant reduction in or even complete remission of psychotic symptoms such as hallucinations and delusions. However, these drugs are not effective in improving cognitive and emotional deficits in patients with schizophrenia. Atypical antipsychotic drugs have a high affinity for the dopamine D receptor, and a modest affinity for the serotonin 5-HT receptor.

Galantamine improves enhanced impulsivity, impairments of attention and long-term potentiation induced by prenatal nicotine exposure to mice.

Prenatal nicotine exposure (PNE) causes behavioral abnormalities in offspring, such as an enhancement of impulsivity and decrease in attention at adolescence. Here we examined the effects of galantamine (GAL) on the behavioral and electrophysiological changes induced by PNE in mice. Pregnant C57BL/6J mice were exposed to nicotine (0.

Paternal valproic acid exposure in mice triggers behavioral alterations in offspring.

Sodium valproate (VPA) is the most widely used antiepileptic drug and is increasingly also being used for several non-epileptic indications including migraines and bipolar disorder. It is known that maternal VPA exposure during pregnancy increases the risk of autism spectrum disorder (ASD) in children. Animal model studies have shown that maternal treatment with VPA in rodents conveys an increased risk for ASD-like phenotypes at the molecular, cellular, and behavioral levels.

Involvement of GAT2/BGT-1 in the preventive effects of betaine on cognitive impairment and brain oxidative stress in amyloid β peptide-injected mice.

In the pathophysiology of Alzheimer's disease (AD), the deposition of amyloid β protein (Aβ) is associated with oxidative stress, leading to cognitive impairment and neurodegeneration. Betaine (glycine betaine or trimethylglycine), known as an osmolyte and methyl donor in mammalian cells, has been reported to suppress the proinflammatory response and oxidative stress in the kidneys, but the effects of betaine on brain diseases remain to be determined. Here, to investigate the effects of betaine treatment on cognitive impairment and the increase in oxidative stress in the brain of an AD animal model, we performed a novel object recognition test and measured the malondialdehyde (MDA; a marker of oxidative stress) levels in the frontal cortex and hippocampus of mice intracerebroventricularly injected with Aβ, an active fragment of Aβ.

Comparison of twice a day and three times a day meropenem administration in elderly patients in a Japanese community hospital.

Meropenem (MEPM) is a broad-spectrum antibiotic prescribed to patients with moderate or severe pneumonia. It is well recognized that appropriate medicine reduces the burden on not only young patients but elderly ones as well. We enrolled 56 patients aged 75 and over who were diagnosed with moderate or severe pneumonia (body temperature: ≧37.

Effect of AceK (acesulfame potassium) on brain function under dietary restriction in mice.

People preferably take zero or low-calorie beverages and foods with artificial sweeteners even though it has been recently suggested that long-term artificial sweetener use affects physiological functions. In addition, a lower body weight was considered to be more healthful, but an abnormally low body weight caused by an excessive diet has been reported to cause health problems. Acesulfame potassium (AceK) is one of the most commonly used for foods and beverages because of its resistance to thermal degradation and marked sweetness.

Prenatal nicotine exposure decreases the release of dopamine in the medial frontal cortex and induces atomoxetine-responsive neurobehavioral deficits in mice.

Increased risk of attention-deficit/hyperactivity disorder (AD/HD) is partly associated with the early developmental exposure to nicotine in tobacco smoke. Emerging reports link tobacco smoke exposure or prenatal nicotine exposure (PNE) with AD/HD-like behaviors in rodent models. We have previously reported that PNE induces cognitive behavioral deficits in offspring and decreases the contents of dopamine (DA) and its turnover in the prefrontal cortex (PFC) of offspring It is well known that the dysfunction of DAergic system in the brain is one of the core factors in the pathophysiology of AD/HD.

Betaine attenuates memory impairment after water-immersion restraint stress and is regulated by the GABAergic neuronal system in the hippocampus.

GABA mediated neuronal system regulates hippocampus-dependent memory and stress responses by controlling plasticity and neuronal excitability. Here, we demonstrate that betaine ameliorates water-immersion restraint stress (WIRS)-induced memory impairments. This improvement was inhibited by a betaine/GABA transporter-1 (GABA transporter-2: GAT2) inhibitor, NNC 05-2090.

Prenatal Nicotine Exposure Impairs the Proliferation of Neuronal Progenitors, Leading to Fewer Glutamatergic Neurons in the Medial Prefrontal Cortex.

Cigarette smoking during pregnancy is associated with various disabilities in the offspring such as attention deficit/hyperactivity disorder, learning disabilities, and persistent anxiety. We have reported that nicotine exposure in female mice during pregnancy, in particular from embryonic day 14 (E14) to postnatal day 0 (P0), induces long-lasting behavioral deficits in offspring. However, the mechanism by which prenatal nicotine exposure (PNE) affects neurodevelopment, resulting in behavioral deficits, has remained unclear.

Dynorphin a (1-13) alleviated stress-induced behavioral impairments in mice.

In this study we investigated whether κ-opioid receptor stimulation by dynorphin A (1-13), a potent fragment of endogenous peptide, attenuated repeated stress-induced behavioral impairments in mice. In order to reduce the motivation to escape, mice were preexposed to inescapable electric footshock (day 0), and then dynorphin A (1-13) was administered to mice prior to the stress from the next day for 4 d (days 1-4). Dynorphin A (1-13) (1500 pmol/5 µL intracerebroventricular (i.

Evaluation of cognitive behaviors in young offspring of C57BL/6J mice after gestational nicotine exposure during different time-windows.

Gestational nicotine exposure is associated with cognitive abnormalities in young offspring. However, practical strategies for prevention or treatment of impaired cognitive behaviors of offspring are not available due to the lack of systematic investigation of underlying mechanism. Therefore, this study aimed at examining the effects of gestational and/or perinatal nicotine exposure (GPNE) on cognitive behaviors in offspring of C57BL/6J mice to provide systematic behavioral data.

Evaluation of emotional behaviors in young offspring of C57BL/6J mice after gestational and/or perinatal exposure to nicotine in six different time-windows.

Nicotine replacement treatments are being alternatively applied as an aid to smoking cessation during pregnancy. However, the effects of nicotine exposed at the prenatal stage on the emotional behaviors in offspring are not well understood due to the lack of systematic investigations. The current study has therefore initially aimed to evaluate emotional behaviors in young mouse offspring (postnatal day 28-36) which experienced gestational and/or perinatal nicotine exposure (GPNE) in six different time-windows.

Effects of betaine on lipopolysaccharide-induced memory impairment in mice and the involvement of GABA transporter 2.

Background: Betaine (glycine betaine or trimethylglycine) plays important roles as an osmolyte and a methyl donor in animals. While betaine is reported to suppress expression of proinflammatory molecules and reduce oxidative stress in aged rat kidney, the effects of betaine on the central nervous system are not well known. In this study, we investigated the effects of betaine on lipopolysaccharide (LPS)-induced memory impairment and on mRNA expression levels of proinflammatory molecules, glial markers, and GABA transporter 2 (GAT2), a betaine/GABA transporter.

Prenatal exposure to PCP produces behavioral deficits accompanied by the overexpression of GLAST in the prefrontal cortex of postpubertal mice.

Altered glutamatergic neurotransmission in the prefrontal cortex (PFC) has been implicated in a myriad of neuropsychiatric disorders. We previously reported that prenatal exposure to PCP produced long-lasting behavioral deficits, accompanied by the abnormal expression and dysfunction of NMDA receptors. In addition, these behavioral changes were attenuated by clozapine treatment.

Evaluation of object-based attention in mice.

The deficits of attention result in significant impairment in daily life, and pharmacological intervention to improve attention is the most effective treatment in clinics. However, methods which are suitable for the large scale preclinical screening of attention-improving compounds or drugs are few in the field. In this study, we have developed object-based attention task as a simple and wherever-practical method that suitable for quick drug screening in mice.

Cilostazol prevents amyloid β peptide(25-35)-induced memory impairment and oxidative stress in mice.

Background And Purpose: Cilostazol may be effective in dementia associated with a cerebral ischaemia. In this study, we examined whether it exerts beneficial effects on learning and/or memory impairment induced by Aβ(25-35) in mice, and compared its effects with those of aspirin.

Experimental Approach: Aβ(25-35) (9 nmol) was administered to mice i.