The <Emphasis Type="Italic">recombination activation gene 1</Emphasis> (<Emphasis Type="Italic">Rag1</Emphasis>) is expressed in a subset of zebrafish olfactory neurons but is not essential for axon targeting or amino acid detection

Background  

Rag1 (Recombination activation gene-1) mediates genomic rearrangement and is essential for adaptive immunity in vertebrates. This gene is also expressed in the olfactory epithelium, but its function there is unknown.     

Adrenalectomy promotes a permanent decrease of plasma corticoid levels and a transient increase of apoptosis and the expression of Transforming Growth Factor β1 (TGF-β1) in hippocampus: effect of a TGF-β1 oligo-antisense

Background  

Corticosterone reduction produced by adrenalectomy (ADX) induces apoptosis in dentate gyrus (DG) of the hippocampus, an effect related to an increase in the expression of the pro-apoptotic gene bax. However it has been reported that there is also an increase of the anti-apoptotic gene bcl-2, suggesting the promotion of a neuroprotective phenomenon, perhaps related to the expression of transforming growth factor β1 (TGF-β1). Thus, we have investigated whether TGF-β1 levels are induced by ADX, and whether apoptosis is increased by blocking the expression of TGF-β1 with an antisense oligonucleotide (ASO) administered intracerebrally in corticosterone depleted rats.     

Transcriptome analysis in primary neural stem cells using a tag cDNA amplification method

Background  

Neural stem cells (NSCs) can be isolated from the adult mammalian brain and expanded in culture, in the form of cellular aggregates called neurospheres. Neurospheres provide an in vitro model for studying NSC behaviour and give information on the factors and mechanisms that govern their proliferation and differentiation. They are also a promising source for cell replacement therapies of the central nervous system. Neurospheres are complex structures consisting of several cell types of varying degrees of differentiation. One way of characterising neurospheres is to analyse their gene expression profiles. The value of such studies is however uncertain since they are heterogeneous structures and different populations of neurospheres may vary significantly in their gene expression.     

Both 5' and 3' flanks regulate Zebrafish brain-derived neurotrophic factor gene expression

Background  

Precise control of developmental and cell-specific expression of the brain-derived neurotrophic factor (BDNF) gene is essential for normal neuronal development and the diverse functions of BDNF in the adult organism. We previously showed that the zebrafish BDNF gene has multiple promoters. The complexity of the promoter structure and the mechanisms that mediate developmental and cell-specific expression are still incompletely understood.     

A non-circadian role for clock-genes in sleep homeostasis:a strain comparison

Background  

We have previously reported that the expression of circadian clock-genes increases in the cerebral cortex after sleep deprivation (SD) and that the sleep rebound following SD is attenuated in mice deficient for one or more clock-genes. We hypothesized that besides generating circadian rhythms, clock-genes also play a role in the homeostatic regulation of sleep. Here we follow the time course of the forebrain changes in the expression of the clock-genes period (per)-1, per2, and of the clock-controlled gene albumin D-binding protein (dbp) during a 6 h SD and subsequent recovery sleep in three inbred strains of mice for which the homeostatic sleep rebound following SD differs. We reasoned that if clock genes are functionally implicated in sleep homeostasis then the SD-induced changes in gene expression should vary according to the genotypic differences in the sleep rebound.     

Genes within the serotonergic system are differentially expressed in human brain

Background  

Serotonin is an important neurotransmitter with wide-ranging functions throughout the central nervous system. There is strong evidence to suggest that regulation of serotonergic gene expression might be related to genetic variability, and several studies have focused on understanding the functional effects of specific polymorphisms within these genes on expression levels. However, the combination of genotype together with gender and brain region could have an overall effect on gene expression. In this study, we report expression patterns of five serotonergic genes (TPH1, TPH2, 5-HT2A, 5-HT2C, 5-HTT) in seven different human post-mortem brain regions (superior frontal gyrus, superior temporal gyrus, striatum, cerebellum, hippocampus, midbrain and thalamus) using TaqMan™ real-time quantitative PCR. In addition, the effect of genotype and gender on their expression levels was determined.     

Tissue-specific and neural activity-regulated expression of human BDNF gene in BAC transgenic mice

Background  

Brain-derived neurotrophic factor (BDNF) is a small secreted protein that has important roles in the developing and adult nervous system. Altered expression or changes in the regulation of the BDNF gene have been implicated in a variety of human nervous system disorders. Although regulation of the rodent BDNF gene has been extensively investigated, in vivo studies regarding the human BDNF gene are largely limited to postmortem analysis. Bacterial artificial chromosome (BAC) transgenic mice harboring the human BDNF gene and its regulatory flanking sequences constitute a useful tool for studying human BDNF gene regulation and for identification of therapeutic compounds modulating BDNF expression.     

Motor coordination deficits in Alpk1 mutant mice with the inserted piggyBac transposon

Background  

ALPK1 (α-kinase 1) is a member of an unconventional alpha-kinase family, and its biological function remains largely unknown. Here we report the phenotypic characterization of one mutant line, in which the piggyBac (PB) transposon is inserted into the Alpk1 gene.     

Expression of Cre recombinase in dopaminoceptive neurons

Background  

Dopamine-activated signaling regulates locomotor and emotional responses and alterations in dopamine-signaling are responsible of several psychomotor disorders. In order to identify specific functions of these pathways, the Cre/loxP system has been used. Here, we describe the generation and the characterization of a transgenic mouse line expressing the Cre recombinase in dopaminoceptive neurons. To this purpose, we used as expression vector a 140 kb yeast artificial chromosome (YAC) containing the dopamine D1 receptor gene (Drd1a).     

Foxo3a induces motoneuron death through the Fas pathway in cooperation with JNK

Background  

Programmed cell death of motoneurons in the developing spinal cord is thought to be regulated through the availability of target-derived neurotrophic factors. When deprived of trophic support, embryonic spinal motoneurons in vitro over-express FasL, a ligand activating a Fas-mediated death pathway. How trophic factors regulate the expression of FasL is presently unclear, but two regulators of FasL, FOXO3a (FKHRL1) and JNK have been described to play a role in other cell types. Thus, their potential function in motoneurons was investigated in this study.     

The neurotrophin receptor p75NTR mediates early anti-inflammatory effects of estrogen in the forebrain of young adult rats

Background  

Estrogen suppresses microglial activation and extravasation of circulating monocytes in young animals, supporting an anti-inflammatory role for this hormone. However, the mechanisms underlying estrogen's anti-inflammatory effects, especially in vivo, are not well understood. The present study tests the hypothesis that anti-inflammatory effects of estrogen are mediated by the pan-neurotrophin receptor p75NTR. Previously, we reported that estrogen attenuated local increases of interleukin(IL)-1β in the NMDA-lesioned olfactory bulb, while further increasing NGF expression.     

Genetic analysis of the GRIK2 modifier effect in Huntington's disease

Background  

In Huntington's disease (HD), age at neurological onset is inversely correlated with the length of the CAG trinucleotide repeat mutation, but can be modified by genetic factors beyond the HD gene. Association of a relatively infrequent 16 TAA allele of a trinucleotide repeat polymorphism in the GRIK2 3'UTR with earlier than expected age at neurological onset has been suggested to reflect linkage disequilibrium with a functional polymorphism in GRIK2 or an adjacent gene.     

Proteomic assessment of a cell model of spinal muscular atrophy

Background  

Deletion or mutation(s) of the survival motor neuron 1 (SMN1) gene causes spinal muscular atrophy (SMA), a neuromuscular disease characterized by spinal motor neuron death and muscle paralysis. Complete loss of the SMN protein is embryonically lethal, yet reduced levels of this protein result in selective death of motor neurons. Why motor neurons are specifically targeted by SMN deficiency remains to be determined. In this study, embryonic stem (ES) cells derived from a severe SMA mouse model were differentiated into motor neurons in vitro by addition of retinoic acid and sonic hedgehog agonist. Proteomic and western blot analyses were used to probe protein expression alterations in this cell-culture model of SMA that could be relevant to the disease.     

Transient change in GABAA receptor subunit mRNA expression in Lurcher cerebellar nuclei during Purkinje cell degeneration

Background  

Lurcher mice suffer from a complete Purkinje cell (PC) loss in the first four postnatal weeks. Parallel to this degeneration, GABAergic synapses in the deep cerebellar nuclei (DCN), the major recipient of the inhibitory PC projection, increase synaptic conductance. Here, we further investigated this phenomenon, using real-time RT-PCR to assess GABA_A receptor subunit gene expression during PC degeneration.     

Dynamic and redundant regulation of LRRK2 and LRRK1 expression

Background  

Mutations within the leucine-rich repeat kinase 2 (LRRK2) gene account for a significant proportion of autosomal-dominant and some late-onset sporadic Parkinson's disease. Elucidation of LRRK2 protein function in health and disease provides an opportunity for deciphering molecular pathways important in neurodegeneration. In mammals, LRRK1 and LRRK2 protein comprise a unique family encoding a GTPase domain that controls intrinsic kinase activity. The expression profiles of the murine LRRK proteins have not been fully described and insufficiently characterized antibodies have produced conflicting results in the literature.     

Chronic NMDA administration to rats increases brain pro-apoptotic factors while decreasing anti-Apoptotic factors and causes cell death

Background  

Chronic N-Methyl-D-aspartate (NMDA) administration to rats is reported to increase arachidonic acid signaling and upregulate neuroinflammatory markers in rat brain. These changes may damage brain cells. In this study, we determined if chronic NMDA administration (25 mg/kg i.p., 21 days) to rats would alter expression of pro- and anti-apoptotic factors in frontal cortex, compared with vehicle control.     

Neural stem cells express melatonin receptors and neurotrophic factors: colocalization of the MT<Subscript>1</Subscript>receptor with neuronal and glial markers

Background  

In order to optimize the potential benefits of neural stem cell (NSC) transplantation for the treatment of neurodegenerative disorders, it is necessary to understand their biological characteristics. Although neurotrophin transduction strategies are promising, alternative approaches such as the modulation of intrinsic neurotrophin expression by NSCs, could also be beneficial. Therefore, utilizing the C17.2 neural stem cell line, we have examined the expression of selected neurotrophic factors under different in vitro conditions. In view of recent evidence suggesting a role for the pineal hormone melatonin in vertebrate development, it was also of interest to determine whether its G protein-coupled MT₁ and MT₂ receptors are expressed in NSCs.