Brain Research. Molecular Brain Research

Although retrograde gene transfer from infected muscles to neurons by viral vectors has been known for years, it is still unknown whether interneuronal gene transportation of viral vectors occurs after retrograde gene transfer. To determine this, we injected adenoviral vectors carrying eGFP gene with or without a neural tracer into the right gastrocnemius muscles of mice. After 7 days, some spinal motor neurons were detected with green fluorescence but without the signal of neural tracer. In addition, nerves with green fluorescence could be noted in the right lumbosacral paraspinal muscles of viral-injected mice...

Current understanding of IGF-I-mediated neuroprotection implies the activation of phosphatidylinositol-3-kinase (PI-3K), which leads to the activation of Akt/Protein Kinase B. In non-neuronal cells, Akt phosphorylates and activates the transcription factor CREB, implicated in the transcription of the anti-apoptotic bcl-2 gene. This paper further analyses the anti-apoptotic IGF-I action in neurons. We show that IGF-I protects cortical neurons against ceramide-induced apoptosis. Ceramide decreases Akt phosphorylation during apoptotic process whereas a simultaneous treatment with IGF-I increases Akt phosphorylation...

Scutellariae radix is a Chinese herbal medicine that has been used to treat disease conditions accompanying inflammation and oxidative stress. In the present study, we examined the effect of Scutellariae radix extracts during acute ethanol exposure in N(2)a neuroblastoma. The Scutellariae radix extracts effectively inhibited ethanol-induced apoptosis and caspase-3/-7 activation. Ethanol induced the expression of caspase-11 that has been known as a dual regulator of pathological apoptosis and inflammatory response...

As estrogens have been implicated in altered cognitive function associated with menopause, the purpose of the present study was to determine the regulatory effects of different estrogen preparations on the expression of estrogen receptor subtypes in the hippocampus and cortex of ovariectomized rats. The expression of estrogen receptor mRNA and protein was determined with RT-PCR and immunohistochemistry, respectively. Two estrogen reagents, Premarin and Progynova, were used in the present study. Premarin, a conjugated equine estrogen, down-regulated ER alpha expression in the hippocampus and cortex of ovariectomized rats and had no effect on levels of ER beta expression in the same two regions...

To assess the molecular effects of the antiepileptic drug clobazam (CLB, 1,5-benzodiazepine), a benzodiazepine effective in the management of epilepsy, we performed a series of experiments using rats with chronic, spontaneous recurrent seizures induced by amygdalar injection of FeCl(3). Experimental animals were treated for 14 days with CLB. We then measured the expression of glutamate and GABA transporter proteins and evaluated the changes that occurred in these proteins using both experimental and control animals...

A constitutive NOS complementary DNA (cDNA) was partially cloned by RT-PCR from the brain of a teleost, the Nile tilapia (Oreochromis niloticus), using degenerate primers against conserved regions of NOS. The predicted 206-long amino acid sequence showed a high degree of identity with other vertebrate neuronal NOS (nNOS) protein sequences. In addition, phylogenetic analysis revealed that Nile tilapia NOS clustered with other known nNOS. Using the coupled reaction of semi-quantitative RT-PCR and Southern blotting, the basal tissue expression pattern of the cloned nNOS gene was investigated in discrete areas of the central nervous system (CNS) and in the heart and skeletal muscle tissue...

Glucocorticoids affect a variety of tissues to enable the organism to adapt to the stress. Hippocampal neurons contain glucocorticoid receptors and respond to elevated glucocorticoid levels by down-regulating the HPA axis. Chronically, however, stress is deleterious to hippocampal neurons. Chronically elevated levels of glucocorticoids result in a decrease in the number of dendritic spines, reduced axonal growth and synaptogenesis, and decreased neurogenesis in the hippocampus. Tolloid-like 1 (Tll-1) is a metalloprotease that potentiates the activity of the bone morphogenetic proteins (BMPs)...

Cocaine is an addictive psychostimulant that induces fos and opioid gene expression by activating the dopamine receptors and the PKA pathways in dopamine D1 and a glutamate NMDA-dependent mechanisms in the striatum. In this study, we show that a single cocaine administration induces ERK phosphorylation in the caudate/putamen of Fischer rats. This increase in Phospho-ERK is diminished by pre-administration of SCH23390, or MK801 but not with pre-administration of eticlopride. Furthermore, this single cocaine administration does not alter the levels of phospho-CREB protein or CREB-DNA bindings in the caudate/putamen protein extracts but does increase phospho-Elk-1 protein levels in the same extracts...

Since 1967, fructose has become the primary commercial sweetener in the food industry. Large amounts of fructose can be toxic and have been correlated with atherosclerosis, malabsorption, hyperuricemia, lactic acidosis, and cataracts. To understand the deleterious and critical role(s) fructose plays in normal metabolism, it is essential to know how and where fructose is metabolized. The fructose transporter, GLUT5, and the specialized enzymes ketohexokinase, aldolase, and triokinase comprise the well-defined fructose-specific metabolic pathway found in liver, kidney, and small intestine...

Allosteric modulation of mouse 5-Hydroxytryptamine(3A) (5-HT(3A)) and 5-HT(3A/B) receptor function by ethanol and trichloroethanol (TCEt) was assessed in HEK293 cells with whole cell patch-clamp electrophysiological recordings. Ethanol enhanced 5-HT(3A) receptor function, but had no effect on mouse 5-HT(3A/B) receptor mediated currents. The enhancing action of trichloroethanol (TCEt) on mouse 5-HT(3A/B) receptor function was much less than that observed in the mouse 5-HT(3A) receptor. Where alcohol-induced increases in peak amplitude were observed, the slope of the 20-80% rising phase of current onset was also enhanced, suggesting that increases in activation rate may be one mechanism through which alcohols enhance function of the 5-HT(3) receptors...

Using cultured rat retinal glial cells, the changes in the expression of glutamate transporters (GLTs) under such conditions as the degree of confluence of the cells, hypoxia, glutamate loading, and potassium loading, were assessed. After the retinal glial cells were isolated from 3-day-old Sprague-Dawley rats, GLAST, GLT-1, and EAAC1 mRNA expression was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and their protein expression was confirmed by Western blot analysis and immunostaining...

The aim of this study was to investigate the expression of cytokines, tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1beta), interleukin-6 (IL-6) and transforming growth factor-beta 1 (TGF-beta1) and chemokines, fractalkine, monocyte chemoattractant protein 1 (MCP-1) and stromal cell-derived factor 1 (SDF-1) in the dorsal motor nucleus of the vagus nerve (DMV) after right vagotomy. Results showed that the immunoreactivities of IL-1beta, IL-6, TGF-beta1, fractalkine and MCP-1 were upregulated in the DMV at 14 days and the upregulation persisted at least until 28 days following right vagotomy...

Hippocampal N-methyl-D-aspartate receptors (NMDARs) contribute to the expression of certain types of synaptic plasticity, such as long-term potentiation (LTP). It is well documented that tyrosine kinases increase NMDAR phosphorylation and potentiate NMDAR function. However, it is unclear how these phosphorylation changes result in enhanced NMDAR activity. We previously reported that NMDAR surface expression can be increased by LTP-inducing stimulation via tyrosine kinase-dependent mechanisms in the adult hippocampus [D...

Estrogen and progesterone play important roles during pregnancy in stimulating the onset of maternal behavior at parturition. The status of receptor expression of these hormones during pregnancy in neural regions that regulate maternal behavior is unclear. The objective of the present study is to characterize changes in neural gene expression of the estrogen receptors alpha and beta (ERalpha and ERbeta) and the progesterone receptor (PR) during the latter part of pregnancy. Brains from primigravid Sprague-Dawley rats were collected on days 15 and 21 of pregnancy...

The mas-related gene (Mrg) family is a large family of G-protein-coupled receptors which are variable in number depending on species. The so-called sensory-neuron-specific receptors (SNSRs) make up a subset of the Mrg family, and several of these have been implicated in nociceptive processes. To verify their specific localization in sensory ganglia, we have determined the expression patterns of two of them, rMrgA and rMrgC, in a panel of rat tissues. The quantitative PCR results in the rat tissue panel indicate that, while several non-neuronal tissues contain significant levels of mRNA for both receptors, these two receptors are most highly expressed in dorsal root ganglia and trigeminal ganglia...

Functional kainate receptors are expressed in the spinal cord substantia gelatinosa region, and their activation contributes to bi-directional regulation of excitatory synaptic transmission at primary afferent synapses with spinal cord substantia gelatinosa neurons. However, no study has reported a role(s) for kainate receptor subtypes in long-term synaptic plasticity phenomena in this region. Using gene-targeted mice lacking glutamate receptor 5 (GLU(K5)) or GLU(K6) subunit, we here show that GLU(K6) subunit, but not GLU(K5) subunit, is involved in the induction of long-term potentiation of excitatory postsynaptic potentials, evoked by two different protocols: (1) high-frequency primary afferent stimulation (100 Hz, 3 s) and (2) low-frequency spike-timing stimulation (1 Hz, 200 pulses)...

Multiple intracellular and extracellular regulatory factors affect transcription of the tyrosine hydroxylase (TH) gene encoding the rate-limiting enzyme in the biosynthesis of the neurotransmitters dopamine, norepinephrine and epinephrine. Short chain fatty acids like butyrate are known to alter TH gene expression, but the mechanism of action is unknown. In this report, transient transfection assays identified the proximal TH promoter to contain sufficient genetic information to confer butyrate responsiveness to a reporter gene...

Tetrahydrobiopterin is a necessary cofactor for the synthesis of nitric oxide by the hemeprotein enzyme, NO-synthase (NOS). It is widely thought that inadequate levels of tetrahydrobiopterin lead to tissue injury and organ dysfunction due, in part, to formation of superoxide from pterin-deficient NOS. In the course of studies on the ubiquitylation of neuronal NOS (nNOS), we have found that certain substrate analogs, such as N(G)-nitro-L-arginine, stabilize the dimeric form of nNOS and protect the enzyme from ubiquitylation...

Behavioral studies have demonstrated that chronic food restriction augments the rewarding and motor-activating effects of centrally injected psychostimulants and direct dopamine (DA) receptor agonists. Recently, it has been shown that intracerebroventricular (i.c.v.) injection of the D-1 DA receptor agonist, SKF-82958, produces an enhanced locomotor-activating effect as well as increased activation of striatal ERK 1/2 MAP kinase, CaM kinase II, CREB, and c-fos in food-restricted (FR) relative to ad libitum fed (AL) rats...

The genetically dystonic rat (SD-dt:JFL) is an autosomal recessive model of generalized dystonia. Without cerebellectomy, the dt rat dies prior to Postnatal Day 40. The dt locus was mapped to a 4.2 Mb region on Chr 7q11 and candidate genes were screened with semi-quantitative RT-PCR. Then, Southern blotting and genomic DNA sequencing identified the 3'-long terminal repeat portion of an intracisternal A particle element inserted into Intron 1 of Atcay, the gene which encodes caytaxin. Northern and Western blotting and quantitative real-time RT-PCR defined the Atcay allele in dt rats (Atcay(dt)) as hypomorphic...