The role of glial autophagy in Alzheimer's disease.

Although Alzheimer's disease is the most pervasive neurodegenerative disorder, the mechanism underlying its development is still not precisely understood. Available data indicate that pathophysiology of this disease may involve impaired autophagy in glial cells. The dysfunction is manifested as reduced ability of astrocytes and microglia to clear abnormal protein aggregates.

Overnight Corticosterone and Gene Expression in Mouse Hippocampus: Time Course during Resting Period.

The aim of the experiment was to test the effect of an elevated level of glucocorticoids on the mouse hippocampal transcriptome after 12 h of treatment with corticosterone that was administered during an active phase of the circadian cycle. Additionally, we also tested the circadian changes in gene expression and the decay time of transcriptomic response to corticosterone. Gene expression was analyzed using microarrays.

Dissection of Mouse Hippocampus with Its Dorsal, Intermediate and Ventral Subdivisions Combined with Molecular Validation.

Many research methods applied in molecular neuroscience require the collection of hippocampal samples, but a still poorly recognized problem is contamination with the choroid plexus during brain dissection. Because of a distinct pattern of gene expression, its inclusion in brain samples can obscure or even confound conclusions drawn from molecular studies. Therefore, we tested our dissection method designed for removal of tissue contamination using expression of the transthyretin gene () as a marker of the choroid plexus.

Stress and the brain transcriptome: Identifying commonalities and clusters in standardized data from published experiments.

Interpretation of transcriptomic experiments is hindered by many problems including false positives/negatives inherent to big-data methods and changes in gene nomenclature. To find the most consistent effect of stress on brain transcriptome, we retrieved data from 79 studies applying animal models and 3 human studies investigating post-traumatic stress disorder (PTSD). The analyzed data were obtained either with microarrays or RNA sequencing applied to samples collected from more than 1887 laboratory animals and from 121 human subjects.

Glucocorticoids, metabolism and brain activity.

The review integrates different experimental approaches including biochemistry, c-Fos expression, microdialysis (glutamate, GABA, noradrenaline and serotonin), electrophysiology and fMRI to better understand the effect of elevated level of glucocorticoids on the brain activity and metabolism. The available data indicate that glucocorticoids alter the dynamics of neuronal activity leading to context-specific changes including both excitation and inhibition and these effects are expected to support the task-related responses. Glucocorticoids also lead to diversification of available sources of energy due to elevated levels of glucose, lactate, pyruvate, mannose and hydroxybutyrate (ketone bodies), which can be used to fuel brain, and facilitate storage and utilization of brain carbohydrate reserves formed by glycogen.

Assessment of Problem-Solving Skills and Inhibitory Control in Mice Using Water Escape Detour Test.

Despite the importance of emotional intelligence, its biological mechanism is still not well understood. For this reason, we have developed a rodent detour task which requires an animal to reach a highly desired object placed directly behind a transparent barrier that blocks the direct route to the target. This apparently simple task is highly dependent on the emotional control that is necessary to inhibit prepotent and counterproductive responses driven by the sight of a desired object.

Scopolamine increases perseveration in mice subjected to the detour test.

Increased perseveration is associated with aging and leads to an impaired ability to cope with problems. Aging is also associated with progressing dysfunction of the cholinergic system which is involved in the regulation of various cognitive processes. Therefore, we tested an effect of an anticholinergic drug on the level of perseveration in mice subjected to the detour test.

Wild Norway Rats Do Not Avoid Predator Scents When Collecting Food in a Familiar Habitat: A Field Study.

The ability to avoid predators is crucial to wild prey animals' survival. Potential danger is signalled, among others, by the presence of predator scents. These odors are used in research both to trigger and to study fear reactions in laboratory animals; they are also employed as repellents against pest rodent species.

Glucocorticoids, genes and brain function.

The identification of key genes in transcriptomic data constitutes a huge challenge. Our review of microarray reports revealed 88 genes whose transcription is consistently regulated by glucocorticoids (GCs), such as cortisol, corticosterone and dexamethasone, in the brain. Replicable transcriptomic data were combined with biochemical and physiological data to create an integrated view of the effects induced by GCs.

Disrupted integration of sensory stimuli with information about the movement of the body as a mechanism explaining LSD-induced experience.

LSD (lysergic acid diethylamide) is a model psychedelic drug used to study mechanism underlying the effects induced by hallucinogens. However, despite advanced knowledge about molecular mechanism responsible for the effects induced by LSD and other related substances acting at serotonergic 5-HT receptors, we still do not understand how these drugs trigger specific sensory experiences. LSD-induced experience is characterised by perception of movement in the environment and by presence of various bodily sensations such as floating in space, merging into surroundings and movement out of the physical body (the out-of-body experience).

Detour Behavior of Mice Trained with Transparent, Semitransparent and Opaque Barriers.

Detour tasks are commonly used to study problem solving skills and inhibitory control in canids and primates. However, there is no comparable detour test designed for rodents despite its significance for studying the development of executive skills. Furthermore, mice offer research opportunities that are not currently possible to achieve when primates are used.

The Effect of Acute and Chronic Social Stress on the Hippocampal Transcriptome in Mice.

Psychogenic stress contributes to the formation of brain pathology. Using gene expression microarrays, we analyzed the hippocampal transcriptome of mice subjected to acute and chronic social stress of different duration. The longest period of social stress altered the expression of the highest number of genes and most of the stress-induced changes in transcription were reversible after 5 days of rest.

Novel candidate genes for alcoholism--transcriptomic analysis of prefrontal medial cortex, hippocampus and nucleus accumbens of Warsaw alcohol-preferring and non-preferring rats.

Objective: Animal models provide opportunity to study neurobiological aspects of human alcoholism. Changes in gene expression have been implicated in mediating brain functions, including reward system and addiction. The current study aimed to identify genes that may underlie differential ethanol preference in Warsaw High Preferring (WHP) and Warsaw Low Preferring (WLP) rats.

Genetic and Epigenetic Mechanisms Linking Pain and Psychiatric Disorders.

The neurophysiological link between neuropathic pain and depression remains unknown despite evident high comorbidity of these two disorders. However, there is convincing evidence that genotype plays a role in both pain and depression. Using various types of genetic analysis - population genetics, cytogenetics and molecular technologies - specific genes have been implicated in mediating almost all aspects of nociception and mood disorders.

Social stress increases expression of hemoglobin genes in mouse prefrontal cortex.

Background: In order to better understand the effects of social stress on the prefrontal cortex, we investigated gene expression in mice subjected to acute and repeated social encounters of different duration using microarrays.

Results: The most important finding was identification of hemoglobin genes (Hbb-b1, Hbb-b2, Hba-a1, Hba-a2, Beta-S) as potential markers of chronic social stress in mice. Expression of these genes was progressively increased in animals subjected to 8 and 13 days of repeated stress and was correlated with altered expression of Mgp (Mglap), Fbln1, 1500015O10Rik (Ecrg4), SLC16A10, and Mndal.

Grand-paternal age and the development of autism-like symptoms in mice progeny.

Advanced paternal age (APA) contributes to the risk of autism spectrum disorders (ASDs) in children. In this study, we used a mouse model to investigate the effects of APA on behavioral features related to autistic syndromes (that is, social deficits, communication impairments and stereotypic/repetitive behaviors). We also examined whether such effects are transmitted across generations.

Stress susceptibility-specific phenotype associated with different hippocampal transcriptomic responses to chronic tricyclic antidepressant treatment in mice.

Background: The effects of chronic treatment with tricyclic antidepressant (desipramine, DMI) on the hippocampal transcriptome in mice displaying high and low swim stress-induced analgesia (HA and LA lines) were studied. These mice displayed different depression-like behavioral responses to DMI: stress-sensitive HA animals responded to DMI, while LA animals did not.

Results: To investigate the effects of DMI treatment on gene expression profiling, whole-genome Illumina Expression BeadChip arrays and qPCR were used.

Recreational use of D-lysergamide from the seeds of Argyreia nervosa, Ipomoea tricolor, Ipomoea violacea, and Ipomoea purpurea in Poland.

Recently, there are important changes in recreational drug use. The aim of the present study was to analyse reports published on a recreational web site by drug users who ingested seeds of plants belonging to the Convolvulaceae family and to compare them with available medical case reports. We have also included reports describing the effects induced by "druids fantasy," which is a new drug allegedly containing the same alkaloid as the seeds of A.

Molecular background of novel silent RHCE alleles.

Background: The absence of expression of C/c and E/e antigens has been associated with rare variant RHCE alleles, referred to as silent RHCE alleles, classically identified among individuals with a rare D- - or Rhnull phenotype. This work reports on different molecular mechanisms identified in three novel silent RHCE alleles.

Study Design And Methods: Samples from D- - or Rhnull individuals and their family members, from families for whom Rh phenotype and/or serologic data were unexplained by inheritance of conventional RH alleles, were analyzed.

Effects of chronic stress on prefrontal cortex transcriptome in mice displaying different genetic backgrounds.

There is increasing evidence that depression derives from the impact of environmental pressure on genetically susceptible individuals. We analyzed the effects of chronic mild stress (CMS) on prefrontal cortex transcriptome of two strains of mice bred for high (HA)and low (LA) swim stress-induced analgesia that differ in basal transcriptomic profiles and depression-like behaviors. We found that CMS affected 96 and 92 genes in HA and LA mice, respectively.

RHD*DOL1 and RHD*DOL2 encode a partial D antigen and are in cis with the rare RHCE*ceBI allele in people of African descent.

Background: Several studies showed in people of African descent the existence of a genetic linkage between RHD alleles encoding a variant D antigen and a given altered RHCE*ce allele. RHCE*ceBI is a rare allele encountered in people of African descent, that encodes a Hr- hr(S) - Rhce protein. Our study shows that RHCE*ceBI appears to be genetically linked to two very similar variant RHD alleles, RHD*DOL1 and RHD*DOL2, and demonstrates for the first time that DOL-2 is a partial D antigen.

Desensitization of GABAergic receptors as a mechanism of zolpidem-induced somnambulism.

Sleepwalking is a frequently reported side effect of zolpidem which is a short-acting hypnotic drug potentiating activity of GABA(A) receptors. Paradoxically, the most commonly used medications for somnambulism are benzodiazepines, especially clonazepam, which also potentiate activity of GABA(A) receptors. It is proposed that zolpidem-induced sleepwalking can be explained by the desensitization of GABAergic receptors located on serotonergic neurons.

Analysis of RhCE variants among 806 individuals in France: considerations for transfusion safety, with emphasis on patients with sickle cell disease.

Background: DNA testing has enabled the documenting of numerous variants of RHCE alleles, especially in individuals of African origin. The risk for production of clinically significant alloantibodies to Rh antigens of patients carrying variant RHCE alleles has led us to analyze the different RhCE variants investigated by molecular biology. Alloimmunization was analyzed regarding the RHCE genetic profile.

Effect of chronic mild stress on hippocampal transcriptome in mice selected for high and low stress-induced analgesia and displaying different emotional behaviors.

There is increasing evidence that mood disorders may derive from the impact of environmental pressure on genetically susceptible individuals. Stress-induced hippocampal plasticity has been implicated in depression. We studied hippocampal transcriptomes in strains of mice that display high (HA) and low (LA) swim stress-induced analgesia and that differ in emotional behaviors and responses to different classes of antidepressants.