A mouse model for intellectual disability caused by mutations in the X-linked 2'‑O‑methyltransferase Ftsj1 gene.

Mutations in the X chromosomal tRNA 2'‑O‑methyltransferase FTSJ1 cause intellectual disability (ID). Although the gene is ubiquitously expressed affected individuals present no consistent clinical features beyond ID. In order to study the pathological mechanism involved in the aetiology of FTSJ1 deficiency-related cognitive impairment, we generated and characterized an Ftsj1 deficient mouse line based on the gene trapped stem cell line RRD143.

Impact of repeated anesthesia with ketamine and xylazine on the well-being of C57BL/6JRj mice.

Within the scope of the 3Rs of Russel and Burch, the number of laboratory animals can be reduced by repeated use of an animal. This strategy only becomes relevant, if the total amount of pain, distress or harm the individual animal experiences does not exceed the severity of a single manipulation. For example, when using imaging techniques, an animal can be examined several times during a study, but it has to be anesthetized each time imaging is performed.

Euthanasia of laboratory mice: Are isoflurane and sevoflurane real alternatives to carbon dioxide?

In the European Union (EU) millions of laboratory mice are used and killed for experimental and other scientific purposes each year. Although controversially discussed, the use of carbon dioxide (CO2) is still permitted for killing rodents according to the Directive 2010/63/EU. Within the scope of refinement, our aim was to investigate if isoflurane and sevoflurane are an appropriate alternative killing method to CO2 in mice.

Systematic Assessment of Well-Being in Mice for Procedures Using General Anesthesia.

In keeping with the 3R Principle (Replacement, Reduction, Refinement) developed by Russel and Burch, scientific research should use alternatives to animal experimentation whenever possible. When there is no alternative to animal experimentation, the total number of laboratory animals used should be the minimum needed to obtain valuable data. Moreover, appropriate refinement measures should be applied to minimize pain, suffering, and distress accompanying the experimental procedure.

Effects of 2-bromoterguride, a dopamine D receptor partial agonist, on cognitive dysfunction and social aversion in rats.

Rationale: 2-Bromoterguride, a dopamine D receptor partial agonist with antagonist properties at serotonin 5-HT receptors and α-adrenoceptors, meets the prerequisites of a putative atypical antipsychotic drug (APD). We recently showed that 2-bromoterguride is effective in tests of positive symptoms of schizophrenia in rats without inducing extrapyramidal side effects or metabolic changes.

Objective: In continuation of our recent work, we now investigated the effect of 2-bromoterguride on apomorphine and phencyclidine (PCP)-induced disruptions of prepulse inhibition (PPI) of the acoustic startle response, a measure of sensory gating.

Development of an algorithm using clinical tests to avoid post-operative residual neuromuscular block.

Background: Quantitative neuromuscular monitoring is the gold standard to detect postoperative residual curarization (PORC). Many anesthesiologists, however, use insensitive, qualitative neuromuscular monitoring or unreliable, clinical tests. Goal of this multicentre, prospective, double-blinded, assessor controlled study was to develop an algorithm of muscle function tests to identify PORC.

Enhanced Stress Response in 5-HTR Overexpressing Mice: Altered HPA Function and Hippocampal Long-Term Potentiation.

Postsynaptic 5-HT receptors (5-HTR) play an important role in anxiety and stress, although their contribution is still controversial. Previous studies report that mice overexpressing postsynaptic 5-HTRs show no changes in basal anxiety, though the influence of stress conditions has not been addressed yet. In this study, we used this animal model to evaluate the role of 5-HTRs in anxiety response after pre-exposure to an acute stressor.

Severity classification of repeated isoflurane anesthesia in C57BL/6JRj mice-Assessing the degree of distress.

According to the EU Directive 2010/63, the severity of a procedure has to be classified as mild, moderate or severe. General anesthesia is thought to be mild, but the Directive does not differentiate between single and repeated anesthesia. Therefore, we investigated the impact of repeated administration of isoflurane, the most commonly used inhalation anesthetic, on the well-being of adult C57BL/6JRj mice, in comparison to single administrations and to untreated animals, when applied six times for 45 min at an interval of 3-4 days.

Therapeutic efficacy of the Ginkgo special extract EGb761 within the framework of the mitochondrial cascade hypothesis of Alzheimer's disease.

Objectives: The mitochondrial cascade hypothesis of dementia assumes mitochondrial dysfunction as an important common pathomechanism for the whole spectrum of age-associated memory disorders from cognitive symptoms in the elderly over mild cognitive impairment to Alzheimer's dementia. Thus, a drug such as the Ginkgo special extract EGb 761 which improves mitochondrial function should be able to ameliorate cognitive deficits over the whole aging spectrum.

Methods: We review the most relevant publications about effects of EGb 761 on cognition and synaptic deficits in preclinical studies as well as on cognitive deficits in man from aging to dementia.

Increased adult neurogenesis in mice with a permanent overexpression of the postsynaptic 5-HT receptor.

Depression is among the leading causes of disability and disease burden. Recent studies point to an involvement of altered serotonin receptor (5-HTR) -mediated adult neurogenesis in depression. However, the exact underlying mechanisms remain unclear, mainly due to the complexity of the serotonergic system with its various receptors and their locations.

Neuromuscular Recovery Is Prolonged After Immobilization or Superimposition of Inflammation With Immobilization Compared to Inflammation Alone: Data From a Preclinical Model.

Objectives: Recovery from ICU-acquired muscle weakness extends beyond hospital stay. We hypothesized that immobilization, more than inflammation, plays a prominent role in the delayed recovery from critical illness.

Design: Prospective, randomized, controlled, experimental study.

2-Bromoterguride-a potential atypical antipsychotic drug without metabolic effects in rats.

Rationale: Recently, we showed that 2-bromoterguride acted as a dopamine D2 receptor partial agonist, a serotonin 5-HT2A and α2C-adrenergic receptor antagonist, and exhibited antidopaminergic efficacy in amphetamine-induced locomotion (AIL) in rats without inducing catalepsy.

Objective: To extend our knowledge on the antipsychotic effects of 2-bromoterguride, we used convergent preclinical animal models and tests; i.e.

Denervation versus pre- and postsynaptic muscle immobilization: Effects On acetylcholine- and muscle-specific tyrosine kinase receptors.

Introduction: Functional immobility of the diaphragm by mechanical ventilation impairs neuromuscular transmission and may result in ventilator-induced diaphragmatic dysfunction. We compared 3 diaphragmatic immobilization models with respect to their effects on expression of adult and fetal acetylcholine receptors (AChRs), muscle-specific receptor tyrosine kinase (MuSK), and muscle fiber morphology.

Methods: Diaphragms of rats were immobilized by either: (1) phrenicotomy; (2) presynaptic tetrodotoxin nerve blockade; or (3) postsynaptic polyethylene orthosis.

Food Deprivation, Body Weight Loss and Anxiety-Related Behavior in Rats.

In behavioral studies, food deprivation protocols are routinely used to initiate or maintain motivational states that are required in a particular test situation. However, there is limited evidence as to when food deprivation compromises animal welfare. This study investigated the effects of different lengths of food deprivation periods and restricted (fixed-time) feeding on body weight loss as well as anxiety-related and motivated behavior in 5-6 month old male and female Wistar rats.

Modulatory Role of Postsynaptic 5-Hydroxytryptamine Type 1A Receptors in (±)-8-Hydroxy-N,N-dipropyl-2-aminotetralin-Induced Hyperphagia in Mice.

Brain serotonin (5-HT) is involved in the control of food intake. The ingestive effects of 5-HT are mediated by various receptor subtypes, among others the 5-HT1A receptor. While the involvement of presynaptic 5-HT1A receptors is regarded as certain, the role of postsynaptic 5-HT1A receptors is rather vague.

Electromyographic permutation entropy quantifies diaphragmatic denervation and reinnervation.

Spontaneous reinnervation after diaphragmatic paralysis due to trauma, surgery, tumors and spinal cord injuries is frequently observed. A possible explanation could be collateral reinnervation, since the diaphragm is commonly double-innervated by the (accessory) phrenic nerve. Permutation entropy (PeEn), a complexity measure for time series, may reflect a functional state of neuromuscular transmission by quantifying the complexity of interactions across neural and muscular networks.

Serotonin controlling feeding and satiety.

Serotonin has been implicated in the control of satiety for almost four decades. Historically, the insight that the appetite suppressant effect of fenfluramine is linked to serotonin has stimulated interest in and research into the role of this neurotransmitter in satiety. Various rodent models, including transgenic models, have been developed to identify the involved 5-HT receptor subtypes.

Neuromuscular blockade improves surgical conditions (NISCO).

Background: We examined the impact of muscle relaxation on surgical conditions and patients' postoperative outcome during elective laparoscopic cholecystectomy under balanced anaesthesia.

Methods: After approval and consent, 57 anaesthetized patients were randomly assigned to group no neuromuscular blockade (No NMB) and deep neuromuscular blockade (Deep NMB), i.e.

Role of 5-HT(1A)- and 5-HT(2A) receptors for the murine model of the serotonin syndrome.

Introduction: The serotonin (5-HT) syndrome (SS) in man covers side effects of drugs in over dose that increase synaptic 5-HT concentration or directly activate 5-HT receptors. The SS is characterized by mental state alterations, neuromuscular excitation, and autonomic dysregulation. In mice, a set of behavioral and autonomic responses can be induced by the same serotonergic drugs as in man.

The murine serotonin syndrome - evaluation of responses to 5-HT-enhancing drugs in NMRI mice.

In humans, the ingestion of the combination of two or more serotonin (5-HT)-enhancing drugs but also of a single drug in overdose can induce serious adverse effects, which are characteristics of the serotonin syndrome (SS). In mice, acute administration of direct and indirect 5-HT agonists also leads to behavioral and autonomic responses, but in literature different responses are thought to be essential. In order to detect common behavioral SS responses induced by 5-HT-enhancing drugs with different mechanisms of action, we investigated the effects of the 5-HT precursor 5-hydroxy-l-tryptophan (5-HTP), the selective serotonin reuptake inhibitor (SSRI) fluoxetine (FLX), and the monoaminooxidase (MAO) inhibitor tranylcypromine (TCP) in male NMRI mice.

The impact of cafeteria diet feeding on physiology and anxiety-related behaviour in male and female Sprague-Dawley rats of different ages.

There is emerging experimental evidence that hyper-energetic diets not only cause obesity but also impact on behaviour in rodents. A hyper-energetic comfort diet/cafeteria diet (CD) fed during early development programmes anxiety-related behaviour in adult age, but little is known how an obesogenic CD impacts on behaviour when fed at a later age. To this end we fed CD to Sprague-Dawley rats of both sexes at either 6 weeks or 12 months old, for a period of 6 weeks.

Sugammadex as a reversal agent for neuromuscular block: an evidence-based review.

Sugammadex is the first clinical representative of a new class of drugs called selective relaxant binding agents. It has revolutionized the way anesthesiologists think about drug reversal. Sugammadex selectively binds rocuronium or vecuronium, thereby reversing their neuromuscular blocking action.

Animal models of the serotonin syndrome: a systematic review.

The serotonin syndrome (SS) is a potentially life-threatening disorder in humans which is induced by ingestion of an overdose or by combination of two or more serotonin (5-HT)-enhancing drugs. In animals, acute administration of direct and indirect 5-HT agonists also leads to a set of behavioral and autonomic responses. In the current review, we provide an overview of the existing versions of the animal model of the SS.