Anxiolytic and antidepressants' effect of Crataegus pinnatifida (Shan Zha): biochemical mechanisms.

Depression and anxiety disorders are highly prevalent. Selective serotonin reuptake inhibitors (SSRIs) are the current first-line treatment for depression, but they have pronounced limitations. Traditional Chinese medicine can serve as a safe and effective alternative to conventional drugs, particularly since many herbal remedies have already been approved for human use as food additives, making the transition from bench to bedside more efficient.

Moderation of the transgenerational transference of antenatal stress-induced anxiety.

Maternal stress has debilitating implications for both mother and child, including increased risk for anxiety. The current COVID-19 pandemic escalates these phenomena, thus, urging the need to further explore and validate feasible therapeutic options. Unlike the protracted nature of clinical studies, animal models could offer swift evidence.

Cerebral MAO Activity Is Not Altered by a Novel Herbal Antidepressant Treatment.

Inhibition of monoamine oxidase (MAO)-A/B can ameliorate depressive- and anxiety-related symptoms via increase of monoamine extracellular levels. However, such inhibition can also instigate hypertensive response following exposure to dietary tyramine (i.e.

GABA Receptor Density Is Not Altered by a Novel Herbal Anxiolytic Treatment.

Anxiety disorders are highly prevalent and considered a major public health concern worldwide. Current anxiolytics are of limited efficacy and associated with various side effects. Our novel herbal treatment (NHT), composed of four constituents, was shown to reduce anxiety-like behavior while precluding a common side effect caused by current anxiolytics, i.

The Impact of Chronic Early Administration of Psychostimulants on Brain Expression of BDNF and Other Neuroplasticity-Relevant Proteins.

Frequently, healthy individuals, children, and students are using stimulants to treat attention deficit hyperactivity disorder (ADHD)-like symptoms or to enhance cognitive capacity, attention and concentration. Methylphenidate, the most common treatment for ADHD, similarly to cocaine, blocks the dopamine reuptake, leading to increase in dopamine level in the synaptic cleft. Brain-derived neurotrophic factor (BDNF) and other neuroplasticity-relevant proteins have a major role in cellular plasticity during development and maturation of the brain.

Alterations in brain neurotrophic and glial factors following early age chronic methylphenidate and cocaine administration.

Attention deficit hyperactivity disorder (ADHD) overdiagnosis and a pharmacological attempt to increase cognitive performance, are the major causes for the frequent (ab)use of psychostimulants in non-ADHD individuals. Methylphenidate is a non-addictive psychostimulant, although its mode of action resembles that of cocaine, a well-known addictive and abused drug. Neuronal- and glial-derived growth factors play a major role in the development, maintenance and survival of neurons in the central nervous system.

Escitalopram or novel herbal mixture treatments during or following exposure to stress reduce anxiety-like behavior through corticosterone and BDNF modifications.

Anxiety disorders are a major public health concern worldwide. Studies indicate that repeated exposure to adverse experiences early in life can lead to anxiety disorders in adulthood. Current treatments for anxiety disorders are characterized by a low success rate and are associated with a wide variety of side effects.

Promiscuous gating modifiers target the voltage sensor of K(v)7.2, TRPV1, and H(v)1 cation channels.

Some of the fascinating features of voltage-sensing domains (VSDs) in voltage-gated cation channels (VGCCs) are their modular nature and adaptability. Here we examined the VSD sensitivity of different VGCCs to 2 structurally related nontoxin gating modifiers, NH17 and NH29, which stabilize K(v)7.2 potassium channels in the closed and open states, respectively.

Rasagiline prevents neurodegeneration in thiamine deficient rats-a longitudinal MRI study.

Neuroprotection is a therapeutic approach for the management of neurodegenerative diseases. Experimental thiamine deficiency (TD) in rats provides a model for selective neurodegeneration accompanied by chronic oxidative deficits. Rats exhibit neurological and cognitive impairments, which can be partially reversed by thiamine administration, enabling the study of mechanisms of neurodegeneration as well as neuroprotection.

A novel herbal treatment reduces depressive-like behaviors and increases BDNF levels in the brain of stressed mice.

Aims: Depression is a chronic, recurring and potentially life-threatening illness. Current treatments for depression are characterized by a low success rate and associated with a wide variety of side effects. The aim of the present study was to evaluate the behavioral and biological anti-depressant effects of a novel herbal treatment (NHT), as well as to assess its potential side effects, in comparison to treatment with the selective serotonin reuptake inhibitor escitalopram.

Genome-wide miRNA expression profiling of human lymphoblastoid cell lines identifies tentative SSRI antidepressant response biomarkers.

Aim: Over 30% of patients with major depression do not respond well to first-line treatment with selective serotonin reuptake inhibitors (SSRIs). Using genome-wide expression profiling of human lymphoblastoid cell lines (LCLs) CHL1 was identified as a tentative SSRI sensitivity biomarker. This study reports on miRNAs implicated in SSRI sensitivity of LCLs.

Anxiolytic effects of a novel herbal treatment in mice models of anxiety.

Aims: Anxiety and stress disorders are currently among the ten most important public health concerns, and in recent years, have reached epidemic proportions. The current success rate of treatments for anxiety disorders is not high, reaching 50% at most. These treatments are also associated with a wide variety of side effects.

Decreased serotonin content and reduced agonist-induced aggregation in platelets of patients chronically medicated with SSRI drugs.

Background: Chronic treatment with selective serotonin reuptake inhibitors (SSRIs) reduces the risk and severity of cardiovascular diseases. SSRIs block the serotonin transporter, thereby inhibiting serotonin (5-HT) uptake into presynaptic neurons as well as into platelets where 5-HT is stored in dense granules. When 5-HT is released in response to agonists it enhances platelet aggregation induced by injury-related signals.

Platelet vesicular monoamine transporter 2 density in the disruptive behavior disorders.

In a former study, we reported decreased platelet vesicular monoamine transporter 2 (VMAT2) density (Bmax) in patients with ADHD. The current study aimed at measuring platelet VMAT2 in the disruptive behavior disorders (DBDs) to assess whether this finding is specific to ADHD or generalizable to the broader DBD concept. The study included 13 patients with DBDs aged 10-12 years and 16 healthy volunteers aged 8-17 years.

Altered affinity of the platelet vesicular monoamine transporter 2 to dihydrotetrabenazine in children with major depression.

Platelet vesicular monoamine transporter (VMAT2) binding characteristics were assessed, using high affinity dihydrotetrabenazine ([(3)H]TBZOH) binding, in 14 children with major depression (MDD) and 16 matched controls. All participants underwent a thorough diagnostic evaluation and the levels of depression and anxiety were measured. K (d) values were significantly lower in children with MDD versus controls (2.

Genome-wide expression profiling of human lymphoblastoid cell lines identifies CHL1 as a putative SSRI antidepressant response biomarker.

Aims: Selective serotonin reuptake inhibitors (SSRIs) are the most commonly used class of antidepressants for treating major depression. However, approximately 30% of patients do not respond sufficiently to first-line antidepressant drug treatment and require alternative therapeutics. Genome-wide studies searching for SSRI response DNA biomarkers or studies of candidate serotonin-related genes so far have given inconclusive or contradictory results.

N-methyl-citalopram: A quaternary selective serotonin reuptake inhibitor.

We describe the synthesis and the pharmacological characterization of a new quaternary selective serotonin reuptake inhibitor (SSRI) N-methyl-citalopram (NMC) with periphery restricted action due to its inability to cross the blood brain barrier. NMC recognized and blocked the human platelet serotonin transporter (SERT) with similar affinity to that of citalopram as was evident from competition binding studies with [(3)H]citalopram and uptake studies with [(3)H]5-HT. In contrast, the affinity of NMC to rat brain SERT was 10-fold lower than its parent compound citalopram.

Lack of modulatory effect of short-term repeated electroconvulsive therapy on platelet vesicular monoamine transporter 2 (VMAT2) in depressed patients.

We investigated the effect of electroconvulsive therapy (ECT) on platelet vesicular monoamine-transmitter-transporter 2 (pVMAT2) using high-affinity [(3)H]dihydrotetrabenazine binding to platelet VMAT2 in 11 women and 7 men, aged 53.7 +/- 15.8.

Human lymphoblastoid cell line panels: novel tools for assessing shared drug pathways.

Aims: While powerful in silico tools are emerging for predicting drug targets and pathways, general in vitro tools for assessing such predictions are lacking. We present a novel in vitro method for distinguishing shared versus distinct drug pathways based on comparative cell growth inhibition profiles across a small panel of human lymphoblastoid cell lines (LCLs) from individual donors.

Materials & Methods: LCLs from unrelated healthy donors were examined in parallel for growth inhibition profiles of various drugs, including antidepressants (paroxetine, fluoxetine, fluvoxamine, citalopram, amitriptyline and imipramine); anticancer drugs (5-fluorouracil, 6-mercaptopurine, azathioprine, methotrexate and resveratrol); steroid drugs (dexamethasone, beclomethasone and prednisolone); and antipsychotic drugs (haloperidol and clozapine).

Neurodegeneration in thiamine deficient rats-A longitudinal MRI study.

Selective neurodegeneration accompanied by mitochondrial dysfunction characterizes neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Thiamine deficiency (TD) in rats is a model for the study of cellular and molecular mechanisms that lead to selective neuronal loss caused by chronic oxidative deficits. Neurodegeneration in TD-rats develops over a period of 12 to 14 days and can be partially reversed by thiamine administration.

Neuroprotection by rasagiline in thiamine deficient rats.

Thiamine deficiency (TD) in rats is a model of chronic impairment of oxidative metabolism leading to neuronal loss. TD rats exhibit neuropathological, behavioral and cognitive abnormalities. The aim of this study was to use this syndrome to assess the neuroprotective potential of drugs in a whole animal model.

Decreased M1 muscarinic receptor density in rat amphetamine model of schizophrenia is normalized by clozapine, but not haloperidol.

There is increasing evidence supporting the involvement of the muscarinic-cholinergic system in schizophrenia. We examined the M1 muscarinic receptor density and mRNA expression in brains of a rat amphetamine model of schizophrenia. We also assessed the effect of the model and chronic treatment with haloperidol and clozapine on brain M1 receptor density and gene expression.

Dissociation between rewarding and psychomotor effects of opiates: differential roles for glutamate receptors within anterior and posterior portions of the ventral tegmental area.

The rewarding effects of drugs of abuse are thought to be dependent on the mesocorticolimbic dopamine system, which originates in the ventral tegmental area (VTA) and projects into the nucleus accumbens (NAC) and other forebrain regions. Heroin, by inhibiting GABAergic interneurons in the VTA, induces local dopaminergic activation and release in the NAC terminals. The role of other basic neurotransmitter systems, such as glutamate in the VTA, in mediating the rewarding effect of addictive drugs, is less established.

Involvement of pituitary adenylate cyclase activating polypeptide (PACAP) and its receptors in the mechanism of antidepressant action.

Recent studies have suggested antidepressant involvement in synaptic plasticity, possibly mediated by neurotrophins and neuropeptides. Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide and neuromodulator. Since its discovery, PACAP has been extensively investigated with regard to its neurotrophic properties including regulation of brain-derived neurotrophic factor (BDNF) expression, a neurotrophin postulated to be involved in the mechanism of antidepressant action and etiology of affective disorders.

Reduced platelet vesicular monoamine transporter density in Tourette's syndrome pediatric male patients.

The vesicular monoamine transporter (VMAT2) plays a major role in the synaptic accumulation and quantal release of monoamines. In this study, we assessed high affinity [(3)H]dihydrotetrabenazine binding to platelet VMAT2, in a group of untreated male Tourette's syndrome (TS) patients (age: 8-17.5 years, n=9) and in a group of age- and sex-matched healthy controls (age: 9-16 years, n=16).