Molecular Brain Research最新文献

Expression of agouti-related peptide, neuropeptide Y, pro-opiomelanocortin and leptin receptor isoforms were found in fetal mouse brain at embryonic day 12 (E12). Levels of expression for these genes were altered in brains of E12 fetuses from pregnant dams on a protein-restricted diet, suggesting that the fetal brain is responsive to changes in maternal nutrition prior to birth.

Recent studies have shown that GluR6 is involved in the modulation of neuronal cell death. It has been shown that PKA can phosphorylate recombinant GluR6 homomeric receptors and that this phosphorylation of GluR6 was suggested to underlie an enhancement of whole-cell current responses. Here, we try to find out whether brain ischemia and reperfusion could induce any change in the serine phosphorylation of GluR6. Our results showed that the serine phosphorylation of GluR6 increased in hippocampus during brain ischemia and early reperfusion period. Then, we used several drugs to investigate the mechanism of modulating the serine phosphorylation of GluR6. KT5720, a specific cell-permeable inhibitor of protein kinase A (PKA), had no effect on the increase in serine phosphorylation of GluR6 induced by brain ischemia or reperfusion. On the other hand, KN-62, a selective inhibitor of rat brain Ca²⁺/calmodulin-dependent protein kinase II (CaMKII), diminished the increase in serine phosphorylation of GluR6. Moreover, our results showed that either MK801 (a NMDA receptor antagonist) or Nifedipine (a L-type Ca²⁺ channel (L-VGCC) blocker) decreased the increase in serine phosphorylation. In conclusion, our results suggest that CaMKII, activated through NMDA receptors and L-VGCCs, mediated the serine phosphorylation of GluR6 during brain ischemia and early reperfusion period.

Excitotoxic lesions of the left entorhinal cortex (EC) cause dopamine supersensitivity. In order to determine if these lesions selectively alter the high-affinity state of dopamine D2 receptors (D2^High), these high-affinity states were measured by competition between dopamine and [³H]domperidone in striata from lesioned rats and sham-operated animals. The proportion of D2^High sites was significantly elevated by 200% in the EC-lesioned rats while that of the D1^High sites, measured by dopamine/[³H]SCH23390 competition, was unaltered. These results provide a biochemical basis for behavioral supersensitivity in rats with EC lesions.

The aromatase knockout (ArKO) mouse is estrogen deficient. Using reverse-transcription and real-time PCR, we showed that transcript levels of the N-methyl-d-aspartate (NMDA) receptor subunit NR2B are significantly higher in the hippocampus of female ArKO mice compared to wild-type (WT) littermates. Expression levels of NR1, NR2A, but not NR2C, also tended to be higher in ArKO mice. In the Morris watermaze test for spatial memory, both genotypes displayed equal significant improvement in the latency in locating the invisible platform over the 5-day training period. These findings show that selective loss of estrogen synthesis is associated with changes in NMDA receptor subunit expression in the hippocampus but little change in spatial learning ability.

Data from animal studies and from genetic scans in humans suggest that brain-derived neurotrophic factor (BDNF), a member of the neurotrophic factor family, may be involved in the mechanisms underlying substance abuse. The present study tested the hypothesis that the BDNF-gene Val66Met polymorphism is associated with substance abuse. We studied this polymorphism in 103 methamphetamine- and 200 heroin-dependent cases and 122 normal controls. We also considered the association of this polymorphism with age of onset of substance abuse in the heroin-dependent cases. Significant differences in BDNF Val66Met genotype distribution were found between subjects dependent on methamphetamine (P = 0.046) or heroin (P = 0.045) and controls, suggesting that the lower 66Met carrier frequency is associated with substance abuse. Furthermore, in the heroin-dependent group, the Val/Val homozygotes had a later onset of substance abuse compared with the Met allele carriers. The results suggest that the BDNF Val66Met polymorphism or a nearby locus may be involved in the pathogenesis of substance abuse. Our findings support previous genetic scan results showing that BDNF may contribute to substance abuse vulnerability.

Both phencyclidine (PCP) and methamphetamine (MAP) can cause schizophrenia-like symptoms. To identify the molecules relating to the drug-induced psychotic state, we used serial analysis of gene expression in rodent cerebral cortices isolated 1 h after intraperitoneal injection of saline, PCP (10 mg/kg), or MAP (4 mg/kg). We analyzed a total of 150,000 tags and found significantly up- or down-regulated genes. The number of MAP-, PCP-, and MAP and PCP-reactive tags were 229, 215, and 41, respectively.

Key pathological processes in Alzheimer's disease (AD) include the accumulation of amyloid beta peptide (Aβ) which, in excess, triggers pathological cascades including widespread inflammation, partly reflected by chronic microglial activation.

It has previously been suggested that CD40/CD40L interaction promotes AD like pathology in transgenic mice. Thus, amyloid burden, gliosis and hyperphosphorylation of tau are all reduced in transgenic models of AD lacking functional CD40L.

We therefore hypothesized that cellular events leading to altered APP metabolism, inflammation and increased tau phosphorylation underlying these observations would be regulated at the genomic level.

In the present report, we used the Affymetrix (GeneChip™) oligonucleotide microarray U133A to gain insight into the global and simultaneous transcriptomic changes in response to microglia activation after CD40/CD40L ligation.

As expected, regulation of elements of the NF-κB signaling, chemokine and B cell signaling pathways was observed. Taken together, our data also suggest that CD40 ligation in human microglia specifically perturbs many genes associated with APP processing.

Distribution of neurons immunopositive to antibodies against the “command neuron peptides” (CNPs) encoded by the snail Helix Command-Specific 2 (HCS2) gene was investigated in the nervous system of medicinal leech Hirudo. Immunopositive neurons were found in the leech segmental ganglia, brain and tail ganglionic masses, and peripheral ganglia. The CNPs immunopositive fibers were observed in neuropils of all ganglia and in some nerves. The role of CNPs immunopositive cells in animal behavior and the putative functions of the CNPs neuropeptide family are discussed.

It is firmly established that the onset of maternal behavior in the female rat is stimulated by a combination of hormones that include prolactin (PRL), estradiol (E₂), and progesterone (P₄). Specifically, nulliparous rats display short latencies to respond to foster young when primed with Silastic capsules filled with P₄ and E₂ and then administered PRL centrally to the medial preoptic area (MPOA), an area integrally involved in the expression of maternal behavior in this species. PRL or P₄ treatments alone are ineffective in stimulating the expression of maternal care. Since the actions of PRL in the MPOA appear to be mediated by PRL receptors, it was of interest to determine whether and how treatment with P₄ and E₂ together or separately might alter mRNA expression of the long form of the PRL receptor (PRL-R_L) in the MPOA. Using in situ hybridization histochemistry (ISHH), mRNA expression of the PRL-R_L was measured in the MPOA of ovariectomized, nulliparous rats treated with various combinations of P₄ and E₂. Treatment of animals with P₄ alone for 10 days or with P₄ followed by E₂ for 1 or 4 days resulted in reductions in PRL receptor mRNA expression in the MPOA when compared with the expression in animals treated with E₂ alone or blank capsules. The actions of P₄ on mRNA expression of the PRL-R_L were more pronounced in the dorsal MPOA. Circulating PRL levels collected at the time of sacrifice were elevated in all groups treated with E₂, but no association between PRL levels and receptor mRNA expression within the MPOA was evident. These findings indicate that the dorsal MPOA may be one site of progesterone's action in facilitating prolactin-mediated maternal behavior.