Ketamine - An Imperfect Wonder Drug?

Ketamine is a potent sedative and dissociative anesthetic agent that has been used clinically for over 50 years since it was first developed in the 1960 s as an alternative to phencyclidine (PCP). When compared to PCP, ketamine exhibited a much lower incidence of severe side effects, including hallucinations, leading to its increased popularity in clinical practice. Ketamine was initially used as an anesthetic agent, especially in emergency medicine and in surgical procedures where rapid induction and recovery was necessary.

Clinical characteristics and treatment of psychosis in Parkinson's disease: A narrative review.

Parkinson's disease (PD) is a chronic, progressive, neurodegenerative disorder whose clinical presentation consists of motor and non-motor signs and symptoms. Among the non-motor symptoms, psychosis can occur in the later stages of the disease. Psychosis in PD (PDP) is a common, complex, and significantly disabling disorder associated with poorer quality of life, accelerated cognitive decline, need for hospitalization or institutionalization, and mortality.

Case report: Unilateral paralysis of the hypoglossal nerve as the only clinical sign of clivus meningioma - a case report and literature review.

Introduction: Clivus meningiomas are benign tumors that occur at the skull base in the posterior cranial fossa. Symptoms usually progress several months or years before diagnosis and may include: headache, vertigo, hearing impairment, ataxia with gait disturbances, sensory problems. In the neurological findings, paralysis of the lower cranial nerves is most often seen, which in the later course can be accompanied by cerebellar and pyramidal signs until the development of a consciousness impairment.

Novel hippocampal genes involved in enhanced susceptibility to chronic pain-induced behavioral emotionality.

Altered mood and psychiatric disorders are commonly associated with chronic pain conditions; however, brain mechanisms linking pain and comorbid clinical depression are still largely unknown. In this study, we aimed to identify whether key genes/cellular mechanisms underlie susceptibility/resiliency to development of depressive-like behaviors during chronic pain state. Genome-wide RNA-seq analysis was used to examine the transcriptomic profile of the hippocampus, a limbic brain region that regulates mood and stress responses, from male rats exposed to chronic inflammatory pain.

Prefrontal cortex astroglia modulate anhedonia-like behavior.

Reductions of astroglia expressing glial fibrillary acidic protein (GFAP) are consistently found in the prefrontal cortex (PFC) of patients with depression and in rodent chronic stress models. Here, we examine the consequences of PFC GFAP+ cell depletion and cell activity enhancement on depressive-like behaviors in rodents. Using viral expression of diphtheria toxin receptor in PFC GFAP+ cells, which allows experimental depletion of these cells following diphtheria toxin administration, we demonstrated that PFC GFAP+ cell depletion induced anhedonia-like behavior within 2 days and lasting up to 8 days, but no anxiety-like deficits.

Magnesium suppresses in vivo oxidative stress and ex vivo DNA damage induced by protracted ACTH treatment in rats.

Oxidative stress, arising from disrupted balance between reactive oxygen/nitrogen species (ROS/RNS) and antioxidant defences, has been implicated in the pathogenesis of stress-related disorders. There is a growing body of evidence that supports the relationship between the activity of the hypothalamic-pituitary-adrenal (HPA) stress system, oxidative stress and magnesium (Mg) homeostasis. The present study aimed to explore the gap in our current understanding of antigenotoxic and protective effects of Mg supplementation against excessive ROS production in male rats during chronic treatment with adrenocorticotropic hormone (ACTH).

Prefrontal Cortex Astroglia Modulate Anhedonia-like Behavior.

Reductions of astroglia expressing glial fibrillary acidic protein (GFAP) are consistently found in the prefrontal cortex (PFC) of patients with depression and in rodent chronic stress models. Here, we examine the consequences of PFC GFAP+ cell depletion and cell activity enhancement on depressive-like behaviors in rodents. Using viral expression of diphtheria toxin receptor in PFC GFAP+ cells, which allows experimental depletion of these cells following diphtheria toxin administration, we demonstrated that PFC GFAP+ cell depletion induced anhedonia-like behavior within 2 days and lasting up to 8 days, but no anxiety-like deficits.

Anatomical Brain Changes and Cognitive Abilities in Patients with Obstructive Sleep Apnea Syndrome and Nonalcoholic Fatty Liver Disease.

Obstructive sleep apnea (OSA) is characterized by repetitive complete or partial collapse of the upper airway and reduction of airflow during sleep. It is associated with significantly increased daytime muscle sympathetic nerve activity thought to result from the repetitive intermittent periods of hypoxemia during sleep and brain alterations that are likely to result. Different brain regions are affected by subsequent hypoxia/anoxia.

Hippocampal mitogen-activated protein kinase phosphatase-1 regulates behavioral and systemic effects of chronic corticosterone administration.

Clinical reports indicate a bidirectional relationship between mental illness and chronic systemic diseases. However, brain mechanisms linking chronic stress and development of mood disorders to accompanying peripheral organ dysfunction are still not well characterized in animal models. In the current study, we investigated whether activation of hippocampal mitogen-activated protein kinase phosphatase-1 (MKP-1), a key factor in depression pathophysiology, also acts as a mediator of systemic effects of stress.

Corticosterone as a Potential Confounding Factor in Delineating Mechanisms Underlying Ketamine's Rapid Antidepressant Actions.

Recent research into the rapid antidepressant effect of subanesthetic doses of ketamine have identified a series of relevant protein cascades activated within hours of administration. Prior to, or concurrent with, these activation cascades, ketamine treatment generates dissociative and psychotomimetic side effects along with an increase in circulating glucocorticoids. In rats, we observed an over 3-fold increase in corticosterone levels in both serum and brain tissue, within an hour of administration of low dose ketamine (10 mg/kg), but not with (2R, 6R)-hydroxynorketamine (HNK) (10 mg/kg), a ketamine metabolite shown to produce antidepressant-like action in rodents without inducing immediate side-effects.

A single dose of magnesium, as well as chronic administration, enhances long-term memory in novel object recognition test, in healthy and ACTH-treated rats.

Although a magnesium-mediated attenuation of memory deficits was reported in animal models of ageing and traumatic brain injury, a possible memory enhancement in healthy subjects has not been investigated yet. We used novel object recognition test (NORT) to examine the effects of acute (30 mg/kg) and chronic (50 mg/kg, 28 days) Mg-sulfate treatment on the long-term memory (LTM) in healthy adult male rats, and to test the sustainability of magnesium effects in the models of acute and chronic (21 days) ACTH administration (10 μg/animal), mimicking the stress- and depression-like conditions. A single dose of Mg-sulfate enhanced the LTM retrieval in the 24 h inter-trial NORT protocol, in healthy, as well as in rats acutely treated with ACTH.

Cognitive Changes and Brain Volume Reduction in Patients with Nonalcoholic Fatty Liver Disease.

Studies of psychological condition of patients suffering from nonalcoholic fatty liver disease are rather equivocal about the results: while some claim that NAFLD patients suffer from anxiety and depression more than non-NAFLD controls, others do not withstand those findings. Lower cognitive potentials have also been reported, both in patient related and in animal model-based investigations, and correlated with assessed brain tissue changes. We hypothesized that NAFLD, as a condition, affects the brain tissue and, subsequently, the cognitive state.

The Stress-Induced Transcription Factor NR4A1 Adjusts Mitochondrial Function and Synapse Number in Prefrontal Cortex.

The energetic costs of behavioral chronic stress are unlikely to be sustainable without neuronal plasticity. Mitochondria have the capacity to handle synaptic activity up to a limit before energetic depletion occurs. Protective mechanisms driven by the induction of neuronal genes likely evolved to buffer the consequences of chronic stress on excitatory neurons in prefrontal cortex (PFC), as this circuitry is vulnerable to excitotoxic insults.

Characterization of GABAergic marker expression in the chronic unpredictable stress model of depression.

Evidence continues to build suggesting that the GABAergic neurotransmitter system is altered in brains of patients with major depressive disorder. However, there is little information available related to the extent of these changes or the potential mechanisms associated with these alterations. As stress is a well-established precipitant to depressive episodes, we sought to explore the impact of chronic stress on GABAergic interneurons.

Cariprazine Exhibits Anxiolytic and Dopamine D3 Receptor-Dependent Antidepressant Effects in the Chronic Stress Model.

Background: Cariprazine, a D3-preferring dopamine D2/D3 receptor partial agonist, is a new antipsychotic drug recently approved in the United States for the treatment of schizophrenia and bipolar mania. We recently demonstrated that cariprazine also has significant antianhedonic-like effects in rats subjected to chronic stress; however, the exact mechanism of action for cariprazine's antidepressant-like properties is not known. Thus, in this study we examined whether the effects of cariprazine are mediated by dopamine D3 receptors.

THE REGULATION ROLE OF CAROTID BODY PERIPHERAL CHEMORECEPTORS IN PHYSIOLOGICAL AND PATHOPHYSIOLOGICAL CONDITIONS.

Introduction: The major oxygen sensors in the human body are peripheral chemoreceptors. also known as interoreceptors- as connected with internal organs, located in the aortic arch and in the body of the common carotid artery. Chemoreceptor function under physiological conditions.

Kinase-mediated signaling cascades in mood disorders and antidepressant treatment.

Kinase-mediated signaling cascades regulate a number of different molecular mechanisms involved in cellular homeostasis, and are viewed as one of the most common intracellular processes that are robustly dysregulated in the pathophysiology of mood disorders such as depression. Newly emerged, rapid acting antidepressants are able to achieve therapeutic improvement, possibly in part, through stimulating activity of kinase-dependent signaling pathways. Thus, advancements in our understanding of how kinases may contribute to development and treatment of depression seem crucial.

Current Use of mTOR Inhibitors for the Treatment of Subependymal Giant Cell Astrocytomas and Epilepsy in Patients with TSC.

The serine/threonine kinase mechanistic target of rapamycin (mTOR) is an important sensor of the cellular energy condition which, at the same time, represents a kind of master switch between anabolic and catabolic cellular processes. Tuberous sclerosis complex (TSC) is a genetic disease which is considered to be a prototype of a dysregulated mTOR signaling pathway. The dysregulated mTOR pathway in TSC leads to characteristic structural and physiologic abnormalities in multiple organs.

Comorbidity Factors and Brain Mechanisms Linking Chronic Stress and Systemic Illness.

Neuropsychiatric symptoms and mental illness are commonly present in patients with chronic systemic diseases. Mood disorders, such as depression, are present in up to 50% of these patients, resulting in impaired physical recovery and more intricate treatment regimen. Stress associated with both physical and emotional aspects of systemic illness is thought to elicit detrimental effects to initiate comorbid mental disorders.

Psychological Stress Activates the Inflammasome via Release of Adenosine Triphosphate and Stimulation of the Purinergic Type 2X7 Receptor.

Background: The mechanisms underlying stress-induced inflammation that contribute to major depressive disorder are unknown. We examine the role of the adenosine triphosphate (ATP)/purinergic type 2X7 receptor (P2X7R) pathway and the NLRP3 (nucleotide-binding, leucine-rich repeat, pyrin domain containing 3) inflammasome in interleukin (IL)-1β and depressive behavioral responses to stress.

Methods: The influence of acute restraint stress on extracellular ATP, glutamate, IL-1β, and tumor necrosis factor alpha in hippocampus was determined by microdialysis, and the influence of acute restraint stress on the NLRP3 inflammasome was determined by western blot analysis.

Decreased SGK1 Expression and Function Contributes to Behavioral Deficits Induced by Traumatic Stress.

Exposure to extreme stress can trigger the development of major depressive disorder (MDD) as well as post-traumatic stress disorder (PTSD). The molecular mechanisms underlying the structural and functional alterations within corticolimbic brain regions, including the prefrontal cortex (PFC) and amygdala of individuals subjected to traumatic stress, remain unknown. In this study, we show that serum and glucocorticoid regulated kinase 1 (SGK1) expression is down-regulated in the postmortem PFC of PTSD subjects.

REDD1 is essential for stress-induced synaptic loss and depressive behavior.

Major depressive disorder (MDD) affects up to 17% of the population, causing profound personal suffering and economic loss. Clinical and preclinical studies have revealed that prolonged stress and MDD are associated with neuronal atrophy of cortical and limbic brain regions, but the molecular mechanisms underlying these morphological alterations have not yet been identified. Here, we show that stress increases levels of REDD1 (regulated in development and DNA damage responses-1), an inhibitor of mTORC1 (mammalian target of rapamycin complex-1; ref.