miR-483-5p offsets functional and behavioural effects of stress in male mice through synapse-targeted repression of Pgap2 in the basolateral amygdala.

Severe psychological trauma triggers genetic, biochemical and morphological changes in amygdala neurons, which underpin the development of stress-induced behavioural abnormalities, such as high levels of anxiety. miRNAs are small, non-coding RNA fragments that orchestrate complex neuronal responses by simultaneous transcriptional/translational repression of multiple target genes. Here we show that miR-483-5p in the amygdala of male mice counterbalances the structural, functional and behavioural consequences of stress to promote a reduction in anxiety-like behaviour.

Modulation of brain cation-Cl cotransport via the SPAK kinase inhibitor ZT-1a.

The SLC12A cation-Cl cotransporters (CCC), including NKCC1 and the KCCs, are important determinants of brain ionic homeostasis. SPAK kinase (STK39) is the CCC master regulator, which stimulates NKCC1 ionic influx and inhibits KCC-mediated efflux via phosphorylation at conserved, shared motifs. Upregulation of SPAK-dependent CCC phosphorylation has been implicated in several neurological diseases.

Novel Genetic, Clinical, and Pathomechanistic Insights into TFG-Associated Hereditary Spastic Paraplegia.

Hereditary spastic paraplegias (HSPs) are genetically and clinically heterogeneous axonopathies primarily affecting upper motor neurons and, in complex forms, additional neurons. Here, we report two families with distinct recessive mutations in TFG, previously suggested to cause HSP based on findings in a single small family with complex HSP. The first carried a homozygous c.

Mutations in KPTN cause macrocephaly, neurodevelopmental delay, and seizures.

The proper development of neuronal circuits during neuromorphogenesis and neuronal-network formation is critically dependent on a coordinated and intricate series of molecular and cellular cues and responses. Although the cortical actin cytoskeleton is known to play a key role in neuromorphogenesis, relatively little is known about the specific molecules important for this process. Using linkage analysis and whole-exome sequencing on samples from families from the Amish community of Ohio, we have demonstrated that mutations in KPTN, encoding kaptin, cause a syndrome typified by macrocephaly, neurodevelopmental delay, and seizures.

Stress-induced lipocalin-2 controls dendritic spine formation and neuronal activity in the amygdala.

Behavioural adaptation to psychological stress is dependent on neuronal plasticity and dysfunction at this cellular level may underlie the pathogenesis of affective disorders such as depression and post-traumatic stress disorder. Taking advantage of genome-wide microarray assay, we performed detailed studies of stress-affected transcripts in the amygdala - an area which forms part of the innate fear circuit in mammals. Having previously demonstrated the role of lipocalin-2 (Lcn-2) in promoting stress-induced changes in dendritic spine morphology/function and neuronal excitability in the mouse hippocampus, we show here that the Lcn-2 gene is one of the most highly upregulated transcripts detected by microarray analysis in the amygdala after acute restraint-induced psychological stress.

Lipocalin-2 controls neuronal excitability and anxiety by regulating dendritic spine formation and maturation.

Psychological stress causes adaptive changes in the nervous system directed toward maintaining homoeostasis. These biochemical and structural mechanisms regulate animal behavior, and their malfunction may result in various forms of affective disorders. Here we found that the lipocalin-2 (Lcn2) gene, encoding a secreted protein of unknown neuronal function, was up-regulated in mouse hippocampus following psychological stress.

Neuropsin cleaves EphB2 in the amygdala to control anxiety.

A minority of individuals experiencing traumatic events develop anxiety disorders. The reason for the lack of correspondence between the prevalence of exposure to psychological trauma and the development of anxiety is unknown. Extracellular proteolysis contributes to fear-associated responses by facilitating neuronal plasticity at the neuron-matrix interface.

Plasmin-mediated degradation of laminin gamma-1 is critical for ethanol-induced neurodegeneration.

Background: Alcoholism may result in severe neurological deficits and cognitive impairments. Many of the central effects of ethanol (EtOH) can be explained by upregulation of N-methyl-D-aspartate (NMDA) and downregulation of gamma-aminobutyric acid (GABA) A receptors (GABAA) in response to long-term EtOH consumption. Abrupt ethanol withdrawal (EW) may result in neuronal hyperexcitability leading to hallucinations, seizures, neurodegeneration, and sometimes death.

Initial segment Kv2.2 channels mediate a slow delayed rectifier and maintain high frequency action potential firing in medial nucleus of the trapezoid body neurons.

The medial nucleus of the trapezoid body (MNTB) is specialized for high frequency firing by expression of Kv3 channels, which minimize action potential (AP) duration, and Kv1 channels, which suppress multiple AP firing, during each calyceal giant EPSC. However, the outward K(+) current in MNTB neurons is dominated by another unidentified delayed rectifier. It has slow kinetics and a peak conductance of approximately 37 nS; it is half-activated at -9.

Ethanol-withdrawal seizures are controlled by tissue plasminogen activator via modulation of NR2B-containing NMDA receptors.

Chronic ethanol abuse causes up-regulation of NMDA receptors, which underlies seizures and brain damage upon ethanol withdrawal (EW). Here we show that tissue-plasminogen activator (tPA), a protease implicated in neuronal plasticity and seizures, is induced in the limbic system by chronic ethanol consumption, temporally coinciding with up-regulation of NMDA receptors. tPA interacts with NR2B-containing NMDA receptors and is required for up-regulation of the NR2B subunit in response to ethanol.

Ethanol-induced neurotoxicity is counterbalanced by increased cell proliferation in mouse dentate gyrus.

Chronic ethanol abuse leads to degenerative changes in the hippocampus, which may result in subsequent cognitive impairment. Since the hippocampus retains the ability to produce neurons through adulthood, in the present study we examined if ethanol-induced neuronal loss could be counterbalanced by cell proliferation in mouse dentate gyrus (DG). A total of 14 days of ethanol administration resulted in marked increase in cells positive for TdT-mediated dUTP nick-end labeling in all hippocampal regions studied, indicating that neurons die throughout the hippocampus by apoptotic mechanism.