Developmental Brain Research最新文献

Neurological symptoms are often found in patients with systemic lupus erythematosus, an autoimmune disease. We found an enhanced aggression in young autoimmune-prone NZB mice before expression of autoimmune hemolytic anemia, which was accompanied by an increase in neural activity in the accessory olfactory bulb. The performance of aggressive behavior was correlated with serum IgM level. These results indicate that IgM class autoantibodies could be implicated in brain dysfunction without apparent pathological changes of autoimmune disease.

A new class of sulfatases, SulfFP1/sulf-1 and SulfFP2/sulf-2, has been implicated in the modulation of extracellular signaling by remodeling heparan sulfate through 6-O-endosulfatase activity. Here, we isolated rat SulfFP2 cDNA and examined its expression by in situ hybridization. SulfFP2 expression is abundant and dynamically regulated in the nervous system during development, whereas it is confined to the cerebral cortex, hippocampal CA3 region, and medial habenular nucleus in the adult brain.

Although it has been demonstrated that maternal epilepsy has some harmful effects on newborn individuals, current data concerning the effects of epileptic phenomena in pregnant mothers on newborn pups are still limited. This study was undertaken to investigate the changes in the cerebellum of newborns of pinealectomized rats subjected to experimental epilepsy during pregnancy. In our study, the rats were randomly divided into six groups: intact control group, anesthesia control group, epilepsy group, melatonin-treated epileptic group, surgical pinealectomy group, and group of melatonin treatment following pinealectomy procedure. At 1 month after pinealectomy, an acute grand mal epileptic seizure was induced by 400 IU penicillin-G administration into their intrahippocampal CA3 region during the 13th day of their pregnancy in all animals except intact control group. On the neonatal first day, pups were perfused transcardially and the cerebellums removed were processed for light microscopic and immunohistochemical studies. Normal migration and maturation were determined in the postnatal rat cerebellum in both intact control and anesthesia (ketamine–xylazine) control groups, but the morphological structure of cerebellum in the epilepsy control group corresponded to the early embryonal period. It was found that experimental epilepsy or pinealectomy procedure enhanced nestin immunoreactivity, but exogenous melatonin treatment (30 μg/100 g body weight, i.p.) following pinealectomy inhibited increased nestin expression induced by melatonin deprival in vermis region of newborn rat cerebellum (P < 0.001). Our results confirm that epileptic seizures during pregnancy may impair neurogenesis and neuronal maturation in newborns, which are more dramatic in the presence of melatonin deficiency during pregnancy, explaining more harmful effects of epileptic seizures to embryos of aged mothers. To the best of our knowledge, this is the first study reporting the effects of maternal epilepsy during pregnancy in pinealectomized rats on nestin immunoexpression in the newborn rat cerebellum.

Adolescence is a time of high risk behavior and increased exploration. This developmental period is marked by a greater probability to initiate drug use and is associated with an increased risk to develop addiction and adulthood dependency. Human adolescents are predisposed toward an increased likelihood of risk taking behaviors [M. Zuckerman, Sensation-seeking and the endogenous deficit theory of drug abuse. NIDA Res Monogr. 74 (1986) 59-70.], including drug use or initiation. In the present study, adolescent and adult animals were first tested on several behavioral measures (novel environment exploratory behavior, novel object preference, novelty-induced impulsivity and novelty-induced exploration) which were used to categorize them as high- (HR) or low-responders (LR). The purpose of the present study was to characterize the neurochemical responsivity of the nucleus accumbens septi (NAcc) in HR and LR adolescent and adult animals in response to a systemic challenge of cocaine. Regardless of age, animals that were more reactive when placed in a novel environment had greater cocaine-induced increases in dopamine (DA). Several important and complex neurochemical differences existed between adolescent and adult animals. Adolescent animals that rapidly approached the novel object (i.e., HR) were the only group to show greater cocaine-induced responsivity. However, adult animals that spent less time near the novel object (i.e., LR) were the only group to have greater cocaine-induced responsivity. Adolescent animals that approached a novel object faster (HR) showed an increased dopaminergic (DAergic) response to an acute cocaine challenge. In contrast, adolescent animals that spent less time with the novel object had an increased cocaine-induced DAergic response compared to HR adults. Adults that approached the object less had a greater cocaine-induced DA response relative to HR adults. Finally, cocaine yielded a greater DA response in adolescent animals that showed a high novelty-induced exploration and impulsivity response, whereas the opposite was true for adults. The differences in response to cocaine between ages and groups are likely due to ontogenetic differences in brain regions that are involved in reward and/or stress responsivity.

Epidemiological studies indicate a relationship between water disinfectant by-products (DBP) and adverse pregnancy outcomes (APO) including neural tube defects. These studies suggest that fetal brain may be vulnerable to DBP during early stages of development. Therefore, we examined several molecular markers commonly known to indicate chemical-induced neurotoxicity during fetal brain development following prenatal exposure to the DBP; chloroacetonitrile (CAN).

Pregnant mice, at gestation day 6 (GD6), were treated with a daily oral dose of CAN (25 mg/kg). At GD12, two groups of animals were treated with an i.v. tracer dose of [2-¹⁴C]-CAN. These animals were sacrificed at 1 and 24 h after treatment and processed for quantitative in situ micro-whole-body autoradiography. The remaining groups of animals continued to receive CAN. At GD18, control and treated animals were weighed, anesthetized, and fetuses were obtained and their brains were removed for biochemical and immunohistochemical analyses.

Whole-body autoradiography studies indicate a significant uptake and retention of [2-¹⁴C]-CAN/metabolites (M) in fetal brain (cerebral cortex, hippocampus, cerebellum) at 1 and 24 h. There was a 20% reduction in body weight and a 22% reduction in brain weight of fetuses exposed to CAN compared to controls. A significant increase in oxidative stress markers was observed in various fetal brain regions in animals exposed to CAN compared to controls. This was indicated by a 3- to 4-fold decrease in the ratio of the reduced to oxidized form of glutathione (GSH/GSSG), increased lipid peroxidation (1.3-fold), and increased 8-hydroxy-2-deoxyguanosine levels (1.4-fold). Cupric silver staining indicated a significant increase in the number of degenerating neurons in cortical regions in exposed animals. In animals exposed to CAN there was increase in nuclear DNA fragmentation (TUNEL staining) detected in the cerebral cortex and cerebellum (2-fold increase in apoptotic indices). Caspase-3 activity in cerebral cortex and cerebellum of treated animals were also increased (1.7- and 1.5-fold, respectively). In conclusion, this study indicates that CAN/M crossed the placenta and accumulated in fetal brain tissues where it caused oxidative stress and neuronal apoptosis. These events could predispose the fetus to altered brain development leading to APO as well as behavioral and learning and memory deficits.

Although injured neurons of inferior colliculus (IC) display a robust axonal outgrowth through a lesion site at postnatal day six (P6) in vitro, and are capable to re-innervate their target cells, injured neurons from P10 IC are unable to regenerate their axons across the lesion site. This axonal regenerative failure has been attributed to an increase of expression of inhibitory molecules in endogenous tissue, during development. As a first step to identify such inhibitory molecules, the present study reports the isolation of molecules differentially expressed in the IC during development. A two-directional (forward and backward) suppression subtractive hybridization (SSH) was performed on IC tissue between P6 and P10 stages. One hundred cDNAs from P6 (P6−P10) and 200 cDNAs from P10 (P10−P6)-subtracted libraries were randomly sequenced. A dot-blot screening of sequenced cDNAs revealed the differential expression for the majority of these cDNAs at their respective developmental stage. Then, the analysis of sequenced clones showed that P6 library was highly enriched in molecules expressed early in the development, such as GAP43 or vimentin proteins. By contrast, the P10 library contained mostly molecules expressed at later stages of development in the central nervous system, such as myelin-related proteins. Our results show that SSH is a suitable method for identifying differentially expressed genes in the developing IC. In addition, these results provide a foundation for further studies dealing with molecules involved in the IC development before and at the onset of hearing, some of which being probably involved in the axonal outgrowth mechanism.

We have generated 362 bp and 547 bp partial sequences for Rana pipiens ephrin-A2 and ephrin-A5 mRNA, respectively. Translation homologies for the comparable segments of cDNA of chicken, mouse and human are 90.8, 86.9 and 84.4% for the ephrin-A2 sequence and 85.7, 85.0 and 85.0% for the ephrin-A5 sequence. Digoxigenin-labeled riboprobes were prepared and applied by means of in situ hybridization to whole-mounts of the brains of mature adults and expression patterns in tadpoles were also explored. The RNA probes revealed similar posterior (high) to anterior (low) expression gradients in the adult tectum, demonstrating that both ephrin-As are expressed in the adult Ranid frog tectum. Only the ephrin-A2 probe was tested on tadpole brain, yielding an appropriately graded expression pattern similar to the adult.