Developmental Brain Research

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.

Kirstie H. Stansfield

Cheryl L. Kirstein

Brain Res Dev Brain Res

Neurochemical effects of cocaine in adolescence compared to adulthood

青春期与成年期可卡因的神经化学效应比较

The effects of a single course of antenatal betamethasone on S100B protein concentration were investigated in Fisher 344 rats. On day 20 of gestation, pregnant rats were injected twice 8 h apart with either (1) 170 microg kg(-1) body weight betamethasone ("clinically-equivalent dose", equivalent to 12 mg twice, 24 h apart in humans), (2) half of this dose (equivalent to 6 mg) or (3) vehicle. We report reference values for S100B protein in the serum and different brain regions in both genders at 1, 2, and 21 days after birth. Interestingly, S100B concentration showed a time-dependent and brain region-specific pattern of expression. At P1, S100B was higher in the serum of males compared to females. In addition, we show that both doses of betamethasone decreased S100B concentration in the serum of males at P1, whereas in the hippocampus, it was reduced by the clinically-equivalent dose only. This suggests that lowering the dose of antenatal betamethasone may be less detrimental for brain maturation and therefore we reiterate the need for clinical trials with a low dose regimen.

Matteo Bruschettini

Daniël L.A. van den Hove

Diego Gazzolo

Pierluigi Bruschettini

Carlos E. Blanco

Harry W.M. Steinbusch

A single course of antenatal betamethasone reduces neurotrophic factor S100B concentration in the hippocampus and serum in the neonatal rat

单疗程产前倍他米松降低新生大鼠海马和血清中神经营养因子S100B浓度

Perinatal brain injury is associated with the release of amino acids, principally glutamate and GABA, resulting in massive increases in intracellular calcium and eventual cell death. We have previously demonstrated that independent administration of kainic acid (KA), an AMPA/kainate receptor agonist, or muscimol, a GABA(A) receptor agonist, to newborn rats results in hippocampal damage [Hilton, G.D., Ndubuizu, A., and McCarthy, M.M., 2004. Neuroprotective effects of estradiol in newborn female rat hippocampus. Dev. Brain Res. 150, 191-198; Hilton, G. D., Nunez, J.L. and McCarthy, M.M., 2003. Sex differences in response to kainic acid and estradiol in the hippocampus of newborn rats. Neuroscience. 116, 383-391; Nunez, J.L. and McCarthy, M.M., 2003. Estradiol exacerbates hippocampal damage in a model of preterm infant brain injury. Endocrinology. 144, 2350-2359; Nunez, J.L., Alt, J.J. and McCarthy, M.M., 2003. A new model for prenatal brain damage. I. GABA(A) receptor activation induces cell death in developing rat hippocampus. Exp. Neurol. 181, 258-269]. We now report that KA or muscimol alone administered to immature hippocampal neurons in culture induces significant cell death as evidenced by TUNEL assay. Surprisingly, simultaneous administration of equimolar quantities of these two agonists blocks the effect of either one alone. Moreover, treatment of newborn pups results in less damage compared to either muscimol or KA alone. We further observed that immunoreactivity for the calcium-binding protein, calbindin D(28K), is increased in the brains of pups simultaneously administered KA and muscimol as compared to either alone.

Genell D. Hilton

Adanma Ndubuizu

Joseph L. Nunez

Margaret M. McCarthy

Simultaneous glutamate and GABAA receptor agonist administration increases calbindin levels and prevents hippocampal damage induced by either agent alone in a model of perinatal brain injury

同时给予谷氨酸和GABAA受体激动剂增加钙结合蛋白水平并预防围产期脑损伤模型中单个药物诱导的海马损伤

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 microg/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.

Yiğit Uyanıkgil

Mehmet Turgut

Utku Ateş

Meral Baka

Mine E. Yurtseven

Beneficial effects of melatonin on morphological changes in postnatal cerebellar tissue owing to epileptiform activity during pregnancy in rats: Light and immunohistochemical study

褪黑素对妊娠期癫痫样活动引起的大鼠产后小脑组织形态学改变的有益作用：光镜和免疫组化研究

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.

Satoshi Nagamine

Seiichi Koike

Kazuko Keino-Masu

Masayuki Masu

Expression of a heparan sulfate remodeling enzyme, heparan sulfate 6-O-endosulfatase sulfatase FP2, in the rat nervous system

大鼠神经系统中硫酸乙酰肝素重塑酶，硫酸乙酰肝素6-O-内硫酸酯酶FP2的表达

Mathias V. Schmidt

Melly S. Oitzl

Seymour Levine

E. Ronald de Kloet

Corrigendum to “The HPA system during the postnatal development of CD1 mice and the effects of maternal deprivation” [Dev. Brain Res. 139 (2002) 39–49]

“CD1小鼠产后发育过程中的HPA系统及母体剥夺的影响”一文的勘误 [Dev. Brain Res. 139 (2002) 39–49]

In cat visual cortex, neurons acquire progressively mature functional properties during the first postnatal months. The aim of this study was to analyze the development of astrocytes during this period. The patterns of expression of the glial fibrillary acidic protein (GFAP) as well as of two gap junction proteins expressed in astrocytes, connexin43 (Cx43) and connexin30 (Cx30), were investigated by immunohistochemistry and optical density measurements, in visual cortical areas 17 and 18 at four different ages: 2 weeks (postnatal days 12 to 15, P12-15), 1 month (P27-31), 2 months (P60-62) and beyond 1 year. Since visual experience is a key factor for neural development, the patterns of expression of these three proteins were studied both in normally-reared and monocularly deprived animals. Interestingly, the distribution of GFAP, Cx43 and Cx30 was found to change dramatically but independently of visual experience, during postnatal development, even beyond P60. During the first postnatal month, GFAP and Cx43 were mainly localized in the white matter underlying the visual cortical areas 17 and 18. Then, their distributions evolved similarly with a progressive decrease of their density in the white matter associated with an increase in the cortex. Connexin30 expression appeared only from the second postnatal month, strictly in the cortex and with a laminar distribution which was similar to that of Cx43 at the same age. In adults, a specific laminar distribution was observed, that was identical for GFAP, Cx43 and Cx30: their density was higher in layers II/III and V than in the other cortical layers.

N. Rochefort

N. Quenech'du

P. Ezan

C. Giaume

C. Milleret

Postnatal development of GFAP, connexin43 and connexin30 in cat visual cortex

猫视觉皮层中GFAP、连接蛋白43和连接蛋白30的产后发育

GABA and its receptors show particular ontogenic distributions in different rat brain areas. Recently, GABAB receptors (GBR) have been described to assemble as heterodimers formed by a GBR1a/b and a GBR2 subunit. Here, the ontogeny of rat GBRs and the pattern of subunit expression in both sexes were determined in the hypothalamus, a critical area for homeostatic regulation. Male and female rats were sacrificed at 1, 4, 12, 20, 28, 38 days of life and at adulthood and hypothalami were removed and frozen. Western blots analysis for GBR1 and GBR2 subunits showed that both were expressed in male and female hypothalamic membranes from day 1 to adulthood. In females, both GBR1a and GBR1b were maximally expressed in newborns and decreased towards adulthood. At birth, expression of GBR1a was significantly higher than GBR1b, while at 38 days, GBR1b was more abundant. In males, GBR1a and GBR1b expression was higher in young animals and decreased gradually showing adult levels between the second and third weeks of age without differences between isoforms. Comparing GBR1 variants levels in hypothalamus between sexes, GBR1a was significantly more abundant in females at birth while at 38 days its expression was higher in males; GBR1b showed no sex differences along development. GBR2 was detected in hypothalami of females and males at all ages; maximum levels were observed at 12 days and adult levels were attained at 38 days, without sex differences. This is the first report on the ontogeny of hypothalamic GABAB receptors in male and female rats, with a particular developmental pattern of subunit and isoform expression and presenting some sex differences.

María S. Bianchi

Victoria A. Lux-Lantos

Bernhard Bettler

Carlos Libertun

Expression of gamma-aminobutyric acid B receptor subunits in hypothalamus of male and female developing rats

雄性和雌性发育期大鼠下丘脑中γ-氨基丁酸B受体亚基的表达

Deficits in social behavior are found in several neuro-psychiatric disorders with a presumed developmental origin. The aim of the present study is to determine if prenatal stress at a given day of gestation alters social behavior in adult offspring. Pregnant rats were exposed to an acute stress (presence of a cat) either at the 10th (S10), the 14th (S14) or the 19th (S19) gestational day. When adult, their offsprings were studied in anxiety, neophobic and social behaviors. The results showed that S10 and S19 rats were more anxious and less aggressive than control rats, while the anxious and aggressive behavior of S14 rats was similar to that of the control ones. It is suggested that day 14 of pregnancy is a hyposensitive period to stressful agents due to an important plasticity of the developing gross nervous structures.

V. Patin

B Lordi

A. Vincent

J. Caston

Effects of prenatal stress on anxiety and social interactions in adult rats

孕期应激对成年大鼠焦虑及社会交往的影响

The present work was conducted to study the cellular composition and developmental capacity of retinal neurospheres. Furthermore, the ability of grafted neurospheres to integrate into adult retinal tissue was studied in an in vitro model. Retinal progenitor cells isolated from rat embryos were expanded into neurospheres in vitro in the presence of basic fibroblast growth factor (bFGF), epidermal growth factor (EGF) and leukemia inhibitory factor (LIF). Neurospheres labeled with a lipophilic dye were placed onto explants, and tissue interactions were analyzed after 2–6 days of culture. Immunocytochemical analysis of neurospheres revealed the presence of neuronal and glial cells. Proliferating neuronal and glial cells were observed after 2 weeks, whereas the neuronal cell proliferation declined considerably after 4 weeks. Few apoptotic cells were observed in the neurospheres. Neurospheres cultured on explanted adult retina engrafted with the surrounding tissue, but progenitor cell migration into the explants was low. However, the grafted neurospheres appeared to limit the experimentally induced photoreceptor apoptosis in the surrounding explant tissue.

Ingela Liljekvist-Larsson

Kjell Johansson

Retinal neurospheres prepared as tissue for transplantation

视网膜神经球作为移植组织制备

Publication Information	Publisher: Elsevier B.V.，Publishing cycle: ，Journal Type: journal，Open Access Journals: No
Basic data	Year of publication: 1981，Proportion of original research papers: ，Self Citation Rate:， Gold OA Rate:

Developmental Brain Research

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