The Sobering Sting: Oleoyl Serotonin Is a Novel Snail Venom-Derived Antagonist of Cannabinoid Receptors That Counteracts Learning and Memory Deficits.

Cannabinoid receptors (CB1 and CB2) are promising targets for a better understanding of neurological diseases. Nevertheless, only a few ligands of CB have reached clinical application so far. Venoms are considered as interesting sources of novel biologically active compounds.

Dopamine-mediated striatal activity and function is enhanced in GlyRα2 knockout animals.

The glycine receptor alpha 2 (GlyRα2) is a ligand-gated ion channel which upon activation induces a chloride conductance. Here, we investigated the role of GlyRα2 in dopamine-stimulated striatal cell activity and behavior. We show that depletion of GlyRα2 enhances dopamine-induced increases in the activity of putative dopamine D1 receptor-expressing striatal projection neurons, but does not alter midbrain dopamine neuron activity.

Neurobeachin haploinsufficient mice display sex-independent alterations in cued and contextual fear conditioning.

Neurobeachin ( NBEA ) is a cytoplasmic protein that regulates receptor trafficking, neurotransmitter and hormone secretion, as well as synaptic connectivity. Recently, hippocampus-dependent contextual extinction, the gradual decrease of a conditioned fear response to a context, was suggested to be specifically impaired in male mice with Nbea deficiency ( Nbea+/- ). The current study examines the role of sex in this effect and whether Nbea also influences cued fear conditioning.

BAMBI: A new method for automated assessment of bidirectional early-life interaction between maternal behavior and pup vocalization in mouse dam-pup dyads.

Vital early-life dyadic interaction in mice requires a pup to signal its needs adequately, and a dam to recognize and respond to the pup's cues accurately and timely. Previous research might have missed important biological and/or environmental elements of this complex bidirectional interaction, because it often focused on one dyadic member only. In laboratory rodents, the Pup Retrieval Test (PRT) is the leading procedure to assess pup-directed maternal care.

Estimating genetics of body dimensions and activity levels in pigs using automated pose estimation.

Pig breeding is changing rapidly due to technological progress and socio-ecological factors. New precision livestock farming technologies such as computer vision systems are crucial for automated phenotyping on a large scale for novel traits, as pigs' robustness and behavior are gaining importance in breeding goals. However, individual identification, data processing and the availability of adequate (open source) software currently pose the main hurdles.

Astrocyte calcium dysfunction causes early network hyperactivity in Alzheimer's disease.

Dysfunctions of network activity and functional connectivity (FC) represent early events in Alzheimer's disease (AD), but the underlying mechanisms remain unclear. Astrocytes regulate local neuronal activity in the healthy brain, but their involvement in early network hyperactivity in AD is unknown. We show increased FC in the human cingulate cortex several years before amyloid deposition.

Automated procedure to assess pup retrieval in laboratory mice.

All mammalian mothers form some sort of caring bond with their infants that is crucial to the development of their offspring. The Pup Retrieval Test (PRT) is the leading procedure to assess pup-directed maternal care in laboratory rodents, used in a wide range of basic and preclinical research applications. Most PRT protocols require manual scoring, which is prone to bias and spatial and temporal inaccuracies.

Prenatal Radiation Exposure Leads to Higher-Order Telencephalic Dysfunctions in Adult Mice That Coincide with Reduced Synaptic Plasticity and Cerebral Hypersynchrony.

Higher-order telencephalic circuitry has been suggested to be especially vulnerable to irradiation or other developmentally toxic impact. This report details the adult effects of prenatal irradiation at a sensitive time point on clinically relevant brain functions controlled by telencephalic regions, hippocampus (HPC), and prefrontal cortex (PFC). Pregnant C57Bl6/J mice were whole-body irradiated at embryonic day 11 (start of neurogenesis) with X-ray intensities of 0.

MEK inhibition ameliorates social behavior phenotypes in a Spred1 knockout mouse model for RASopathy disorders.

Background: RASopathies are a group of disorders that result from mutations in genes coding for proteins involved in regulating the Ras-MAPK signaling pathway, and have an increased incidence of autism spectrum disorder (ASD). Legius syndrome is a rare RASopathy caused by loss-of-function mutations in the SPRED1 gene. The patient phenotype is similar to, but milder than, Neurofibromatosis type 1-another RASopathy caused by loss-of-function mutations in the NF1 gene.

Restoring miR-132 expression rescues adult hippocampal neurogenesis and memory deficits in Alzheimer's disease.

Neural stem cells residing in the hippocampal neurogenic niche sustain lifelong neurogenesis in the adult brain. Adult hippocampal neurogenesis (AHN) is functionally linked to mnemonic and cognitive plasticity in humans and rodents. In Alzheimer's disease (AD), the process of generating new neurons at the hippocampal neurogenic niche is impeded, yet the mechanisms involved are unknown.

Methylene tetrahydrofolate reductase A1298C polymorphisms influence the adult sequelae of chemotherapy in childhood-leukemia survivors.

This retrospective correlation study investigated the putative link between methylene tetrahydrofolate reductase (MTHFR) A1298C mutations and chemotherapy-related brain function changes in adult childhood-leukemia survivors. To this end, we determined the relationship between the particular MTHFR1298 genotype (AA, AC or CC) of 31 adult childhood-leukemia survivors, and (1) their CSF Tau and phosphorylated Tau (pTau) levels at the time of treatment, (2) their adult performance intelligence quotient (PIQ), and (3) their regional brain connectivity using diffusion magnetic resonance imaging (dMRI) and resting-state functional MRI (rsfMRI). We confirmed that neuropathology markers Tau and pTau significantly increased in CSF of children after intrathecal methotrexate administration.

Effects of orbitofrontal cortex and ventral hippocampus disconnection on spatial reversal learning.

Behavioural flexibility is a cognition-related function that enables subjects to adapt to a changing environment. Orbitofrontal cortex (OFC) and hippocampus (HC) have been involved in cognitive flexibility, but the interaction between these structures might be of particular functional significance. We applied a disconnection model in C57BL/6JRj mice to investigate the importance of OFC and ventral HC (vHC) interaction.

Folic Acid Fortification Prevents Morphological and Behavioral Consequences of X-Ray Exposure During Neurulation.

Previous studies suggested a causal link between pre-natal exposure to ionizing radiation and birth defects such as microphthalmos and exencephaly. In mice, these defects arise primarily after high-dose X-irradiation during early neurulation. However, the impact of sublethal (low) X-ray doses during this early developmental time window on adult behavior and morphology of central nervous system structures is not known.

Spectrum of social alterations in the Neurobeachin haploinsufficiency mouse model of autism.

Autism spectrum disorder (ASD) is a common and pervasive neurodevelopmental disorder, characterized by sexually divergent social deficits. Its etiology is multifactorial with an important contribution of genetic factors. Neurobeachin (Nbea), a brain-enriched multidomain scaffolding protein, is an ASD candidate gene that was found to be translocated or deleted in ASD patients.

Chronic Sodium Selenate Treatment Restores Deficits in Cognition and Synaptic Plasticity in a Murine Model of Tauopathy.

A major goal in diseases is identifying a potential therapeutic agent that is cost-effective and can remedy some, if not all, disease symptoms. In Alzheimer's disease (AD), aggregation of hyperphosphorylated tau protein is one of the neuropathological hallmarks, and Tau pathology correlates better with cognitive impairments in AD patients than amyloid-β load, supporting a key role of tau-related mechanisms. Selenium is a non-metallic trace element that is incorporated in the brain into selenoproteins.

Aged Tmem106b knockout mice display gait deficits in coincidence with Purkinje cell loss and only limited signs of non-motor dysfunction.

Genetic variants in TMEM106B are a major risk factor for several neurodegenerative diseases including frontotemporal degeneration, limbic-predominant age-related TDP-43 encephalopathy, Parkinson's disease, late-onset-Alzheimer's disease and constitute a genetic determinant of differential aging. TMEM106B encodes an integral lysosomal membrane protein but its precise physiological function in the central nervous system remains enigmatic. Presently, we aimed to increase understanding of TMEM106B contribution to general brain function and aging.

Comparison between touchscreen operant chambers and water maze to detect early prefrontal dysfunction in mice.

The relative lack of sensitive and clinically valid tests of rodent behavior might be one of the reasons for the limited success of the clinical translation of preclinical Alzheimer's disease (AD) research findings. There is a general interest in innovative behavioral methodology, and protocols have been proposed for touchscreen operant chambers that might be superior to existing cognitive assessment methods. We assessed and analyzed touchscreen performance in several novel ways to examine the possible occurrence of early signs of prefrontal (PFC) functional decline in the APP/PS1 mouse model of AD.

The FTLD Risk Factor TMEM106B Regulates the Transport of Lysosomes at the Axon Initial Segment of Motoneurons.

Genetic variations in TMEM106B, coding for a lysosomal membrane protein, affect frontotemporal lobar degeneration (FTLD) in GRN- (coding for progranulin) and C9orf72-expansion carriers and might play a role in aging. To determine the physiological function of TMEM106B, we generated TMEM106B-deficient mice. These mice develop proximal axonal swellings caused by drastically enlarged LAMP1-positive vacuoles, increased retrograde axonal transport of lysosomes, and accumulation of lipofuscin and autophagosomes.

Post-weaning infant-to-mother bonding in nutritionally independent female mice.

Infant-parent attachment is highly selective and continues beyond essential care in primates, most prominently in humans, and the quality of this attachment crucially determines cognitive and emotional development of the infant. Altricial rodent species such as mice (Mus musculus) display mutual recognition and communal nursing in wild and laboratory environments, but parental bonding beyond the nursing period has not been reported. We presently demonstrated that socially and nutritionally independent mice still prefer to interact selectively with their mother dam.

EphA4 loss improves social memory performance and alters dendritic spine morphology without changes in amyloid pathology in a mouse model of Alzheimer's disease.

Background: EphA4 is a receptor of the ephrin system regulating spine morphology and plasticity in the brain. These processes are pivotal in the pathophysiology of Alzheimer's disease (AD), characterized by synapse dysfunction and loss, and the progressive loss of memory and other cognitive functions. Reduced EphA4 signaling has been shown to rescue beta-amyloid-induced dendritic spine loss and long-term potentiation (LTP) deficits in cultured hippocampal slices and primary hippocampal cultures.

Noradrenergic and dopaminergic involvement in novelty modulation of aversive memory generalization of adult rats.

The generalization of aversive memory can be defined as the phenomenon in which a situation similar to (but distinctive from) a previous aversive event triggers an avoidance response. This phenomenon has been suggested to play a role in several psychological disorders. In this study, we investigate the effects of novelty on the generalization of fear memories, and the involvement of noradrenergic and dopaminergic systems in this process.