- Email: [email protected]
Effects of prenatal alcohol exposure on social interaction in early and late adolescent male and female rats
106
Abstracts / Int. J. Devl Neuroscience 47 (2015) 1–131
hypoxia decreases expression of synaptic proteins i.e. synaptophysin, PSD-95and synapsin which further validated by western blotting whereas exposing them in enriched environment ameliorate this synaptic loss. Golgi staining reveals protective effect of enriched environment during HH exposure as evident from increased dendritic arborisation, spine density and morphology. Present study also reveals the role of BDNF/TrkB signalling in EE mediated modulation hippocampal synaptic palsitcity. http://dx.doi.org/10.1016/j.ijdevneu.2015.04.288 ISDN2014 0350 The adverse effects of intrauterine growth restriction on fetal cerebral function development Ba Yi Children’s Hospital Affiliated to Beijing Military General Hospital, China Objective: To explore the adverse effects of intrauterine growth restriction (IUGR) on fetal cerebral function development. Methods: Because of most of IUGR fetus will be small for gestational age (SGA) infants, thus, 60 SGA and 40 appropriate gestational age (AGA) infants with a gestational age from 37 weeks to 40+6 weeks who were hospitalized in BaYi Children’s Hospital Affiliated to Beijing Military General Hospital were included in this study. Those patients with fetal distress,birth asphyxia, hyperspasmia, intracranial hemorrhage, periventricular leukomalacia, intracranial infection, septicemia and congenital abnormalities were excluded from stydy. amplitude-integrated electroencephalography(aEEG) (OLYMPIC CFM6000) was used to monitor the baby’s cerebral function within 3 days after birth. The monitoring time lasted for 2-4 h in every infant. The obvervational index included continuity’ sleep wake cycling (SWC) interburst interval (IBI) minimum voltage and maximum voltage, etc. Student’s t-test, Chi-squared test and analyses of variance were used to compare the difference betweent two groups. Results: (1) The continuity: the frequence of aEEG with continuity in SGA and AGA groups were 15.0%(9/60) and 70%(28/40), respectively (x2 = 31.145, p = 0.000). (2)SWC: the frequence of aEEG with SWC in SGA and AGA groups were 15.0%(9/60) and 70%(28/40), respectively (x2 = 31.145, p = 0.000).(3) IBI: the frequence of IBI in SGA and AGA groups were 14.55 ± 0.75 s and 5.09 ± 0.89 s, respectively(t = 57.209, p = 0.000). (4) The maximum voltage: the maximum voltage in SGA and AGA groups were 10.40 ± 2.61 uv and 16.42 ± 5.53 uv, respectively (t = −6.433, p = 0.000). (5) The minimum voltage:the minimum voltage in SGA and AGA groups were 4.02 ± 1.61 uv and 6.98 ± 3.82 uv, respectively(t = −4.632, p = 0.000). (6) Hypoglycemia (without hypoglycemic encephalopathy) or hyperbilirubinemia (without bilirubin encephalopathy) had no significant influence on fetal cerebral function (p > 0.05). Conclusion: The results showed that SGA infants have a poor continuity absence of SWC longer IBI lower maximum voltage and minimum voltage, which suggested that IUGR will resulted adverse influence on fetal cerebral function development to a degree. This work was supported by the Natural Science Foundation of China (81170577). http://dx.doi.org/10.1016/j.ijdevneu.2015.04.289
ISDN2014 0351 The impact of co-morbid seizure disorder on neuropsychological functioning in children and adolescents with FASD Sukhpreet Tamana 1,∗ , Gail Andrew 1 , James Reynolds 2 , Jacqueline Pei 1 , Carmen Rasmussen 1 1 2
University of Alberta, Canada Queens University, Canada
Introduction: Fetal Alcohol Spectrum Disorders (FASD) describes individuals with neuropsychological and behavioral impairments as a result of maternal alcohol consumption. FASD is associated with several co-morbidities including seizure disorder and epilepsy (Bell et al., 2010), which may have temporary or long-lasting structural and neuropsychological effects. However, it is unknown whether individuals with FASD, with and without seizure history, show different impairments in neuropsychological functions. Goal: to determine whether a seizure co-morbidity is associated with increased neuropsychological deficits in FASD. Method: Participants included 26 children and adolescents with FASD (11 with seizure history and 15 without) and 15 typically developing controls aged 7–16 years, which are a subset from the FASD NeuroDevNet project. Groups were matched on age and gender where possible. All children were assessed on selected subtests from the NEPSY-II that included measures of attention and executive functioning, memory, visual-spatial processing; a math test; as well as two parent rating scales measuring executive functioning (BRIEF) and adaptive behavior (ABAS-II). Results: As expected, the FASD group (with and without seizures) performed worse on most tests compared to controls. Importantly, participants with FASD and seizures performed significantly worse than those without seizures on a measure of inhibition. The FASD/seizure group also showed trends towards greater impairments than those without seizures in some areas involving more complex-inhibition and mathematics, but had similar performance in cognitive flexibility and attention. No group differences were found on the BRIEF and ABAS-II. Implications: These preliminary findings indicate that a seizure co-morbidity in FASD may have an increased effect on some neuropsychological domains, highlighting the critical need for more research in this area. These results also have implications for developing appropriate intervention strategies for individuals with FASD and seizure history. http://dx.doi.org/10.1016/j.ijdevneu.2015.04.290 ISDN2014 0352 Effects of prenatal alcohol exposure on social interaction in early and late adolescent male and female rats P.J. Holman ∗ , L.A. Hill, K. Wind, S. Haghighat, N. Mukhi, L. Takeuchi, G.L. Hammond, J. Weinberg Department of Cellular & Physiological Sciences, University of British Columbia, Vancouver, BC, Canada V6T 1Z3 Social behaviour deficits are a pervasive feature across Fetal Alcohol Spectrum Disorders (FASD). Animal models of prenatal alcohol exposure (PAE) have been useful in demonstrating social neurobehavioural deficits, however, more studies are needed to establish a distinctive social neurobehavioural profile that would distinguish FASD from other developmental disorders with social behaviour impairments, including autism spectrum disorder. Social
Abstracts / Int. J. Devl Neuroscience 47 (2015) 1–131
behaviour deficits emerge early and may become more pronounced around adolescence, a critical period of social behaviour development when the transition to a more complex social environment may exacerbate existing social behaviour impairments. Here, we tested social interaction without and with physical contact during adolescence using a well-established animal model of PAE. Pregnant rat dams were assigned to: 1) PAE: access to liquid ethanol diet ad libitum; 2) Pair-Fed: access to liquid control diet yoked to consumption of a PAE partner; or 3) Control: access to control diet ad libitum. Female and male offspring were tested prior to or following pubertal onset, first using a 2-chamber social interaction test in which one chamber was empty (Non-Social) and the other contained a social stimulus rat within a clear partition (Social). The following day, animals were placed in a testing apparatus and then introduced to a novel social stimulus. Social interaction behaviour without and with physical contact was filmed and later analyzed using video tracking and coding software. PAE animals did not differ from controls on the social interaction test without physical contact. However, results from the social interaction test with physical contact indicated PAE-related sexually dimorphic alterations in social behaviour, including increased olfactory investigation in females and increased pouncing in males. These results suggest that social motivation appears not to play a role in the social behaviour deficits following PAE; rather, PAE alters the normal expression of social behaviour in a sexually dimorphic fashion. Supported by NIH/NIAAA R37 AA007789 and R01 AA022460 and NeuroDevNet (Canadian NCE) to JW; PH is a NeuroDevNet Trainee. http://dx.doi.org/10.1016/j.ijdevneu.2015.04.291 ISDN2014 0353 N-cadherin promotes recruitment and migration of neural progenitor cells from the SVZ stem cell niche into demyelinated lesions Michael Klingener 1,2,∗ , Manideep Chavali 2 , Adan Aguirre 1,2 1
Program in Genetics, Stony Brook University, Stony Brook, NY 11794, USA 2 Department of Pharmacology, Stony Brook University, Stony Brook, NY 11794, USA Discrete cellular microenvironments regulate stem cell pools and their development, as well as function in maintaining tissue homeostasis. While the signaling elements modulating neural progenitor cells (NPCs) of the adult subventricular zone (SVZ) niche are fairly well understood, the pathways activated following injury, and the resulting outcomes, are less clear. In the present study, we used mouse models of demyelination and proteomics analysis to identify molecular cues present in the SVZ niche during injury, and analyzed their role on NPCs in the context of promoting myelin repair. Proteomic analysis of SVZ tissue from mice with experimental demyelination identified several proteins that are known to play roles in NPC proliferation, cell adhesion, and migration. Using the findings from this novel approach, we demonstrate a role for N-cadherin as a critical molecular element in promoting recovery following injury. Mechanistically, during the onset of demyelination in the subcortical white matter (SCWM), activation of epidermal growth factor receptor (EGFR) signaling in NPCs of the SVZ stimulates the interaction between N-cadherin and A Disintegrin And Metalloproteinase 10 (ADAM10). Upon cleavage and activation of N-cadherin signaling by ADAM10, NPCs undergo cytoskeletal rearrangement and polarization, enhancing their migration out of the SVZ into demyelinated lesions of the
107
SCWM. Genetically disrupting either EGFR signaling or ADAM10 inhibits this pathway, preventing N-cadherin regulated NPC polarization and migration. Additionally, in vivo experiments employing N-cadherin gain- and loss-of-function approaches demonstrate that N-cadherin enhances the recruitment of SVZ NPCs into demyelinated lesions and rescues the migration deficit observed in Nestin-CreTM /ADAM10fl/fl mice. Our data revealed that EGFRdependent N-cadherin signaling physically initiated by ADAM10 cleavage is a response of the pathological SVZ niche to promote repair of the injured brain. http://dx.doi.org/10.1016/j.ijdevneu.2015.04.292 ISDN2014 0354 The proliferation, lineage and regenerative potential of heterogeneous NG2+ glia cells in the adult cerebral cortex are regulated by continuous environmental cues Fikri Birey 1,2,∗ , Adan Aguirre 2 1
Graduate Program in Genetics, Stony Brook University, Stony Brook, NY 11794, USA 2 Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794, USA E-mail address: fi[email protected] (F. Birey). Abundantly found throughout the developing and mature CNS, NG2-expressing glia (NG2+ glia) are the most proliferative cell type in the CNS and are highly responsive to various kinds of brain injury. It has largely been assumed that NG2+ glia represent a homogenous cell population based on their proliferative and lineage capacities, both under physiological and pathological conditions. Yet, the full lineage and regenerative potential of NG2+ glia remain controversial in the adult cerebral cortex. To unravel cell-intrinsic abilities of NG2+ glia in the adult cerebral cortex, we developed a transgenic line to ablate NG2+ glia and examined the repopulation of NG2+ glia in situ after their massive depletion, therefore capturing the majority of these progenitors in their regenerative-like state as in during early CNS development. During the repopulation of the brain parenchyma, we observed two populations of NG2+ cells based in their proliferative dynamics; an active dividing and a quiescent NG2+ glia population. Interestingly, quiescent NG2+ cells that escape depletion are the principal cells that take charge to repopulate the depleted brain parenchyma. Furthermore, we show that the proliferation, repopulation and tile-like distribution characteristics of NG2+ glia is mediated by the netrin-1 signalling. NG2+ cells displayed a tri-potent lineage potential during this condition, hence generating along with NG2+ cells, oligodendrocytes and small but significant amount of neurons in the cortex. Finally, combining a mouse model of white matter injury and the NG2+ glia depletion system, we demonstrate increased efficiency in remyelination due to increased oligodendrocyte population. Our data demonstrate that the optimal distribution cues regulate heterogeneous NG2+ glia proliferative and lineage potentials in the adult cortex. http://dx.doi.org/10.1016/j.ijdevneu.2015.04.293
Abstracts / Int. J. Devl Neuroscience 47 (2015) 1–131
hypoxia decreases expression of synaptic proteins i.e. synaptophysin, PSD-95and synapsin which further validated by western blotting whereas exposing them in enriched environment ameliorate this synaptic loss. Golgi staining reveals protective effect of enriched environment during HH exposure as evident from increased dendritic arborisation, spine density and morphology. Present study also reveals the role of BDNF/TrkB signalling in EE mediated modulation hippocampal synaptic palsitcity. http://dx.doi.org/10.1016/j.ijdevneu.2015.04.288 ISDN2014 0350 The adverse effects of intrauterine growth restriction on fetal cerebral function development Ba Yi Children’s Hospital Affiliated to Beijing Military General Hospital, China Objective: To explore the adverse effects of intrauterine growth restriction (IUGR) on fetal cerebral function development. Methods: Because of most of IUGR fetus will be small for gestational age (SGA) infants, thus, 60 SGA and 40 appropriate gestational age (AGA) infants with a gestational age from 37 weeks to 40+6 weeks who were hospitalized in BaYi Children’s Hospital Affiliated to Beijing Military General Hospital were included in this study. Those patients with fetal distress,birth asphyxia, hyperspasmia, intracranial hemorrhage, periventricular leukomalacia, intracranial infection, septicemia and congenital abnormalities were excluded from stydy. amplitude-integrated electroencephalography(aEEG) (OLYMPIC CFM6000) was used to monitor the baby’s cerebral function within 3 days after birth. The monitoring time lasted for 2-4 h in every infant. The obvervational index included continuity’ sleep wake cycling (SWC) interburst interval (IBI) minimum voltage and maximum voltage, etc. Student’s t-test, Chi-squared test and analyses of variance were used to compare the difference betweent two groups. Results: (1) The continuity: the frequence of aEEG with continuity in SGA and AGA groups were 15.0%(9/60) and 70%(28/40), respectively (x2 = 31.145, p = 0.000). (2)SWC: the frequence of aEEG with SWC in SGA and AGA groups were 15.0%(9/60) and 70%(28/40), respectively (x2 = 31.145, p = 0.000).(3) IBI: the frequence of IBI in SGA and AGA groups were 14.55 ± 0.75 s and 5.09 ± 0.89 s, respectively(t = 57.209, p = 0.000). (4) The maximum voltage: the maximum voltage in SGA and AGA groups were 10.40 ± 2.61 uv and 16.42 ± 5.53 uv, respectively (t = −6.433, p = 0.000). (5) The minimum voltage:the minimum voltage in SGA and AGA groups were 4.02 ± 1.61 uv and 6.98 ± 3.82 uv, respectively(t = −4.632, p = 0.000). (6) Hypoglycemia (without hypoglycemic encephalopathy) or hyperbilirubinemia (without bilirubin encephalopathy) had no significant influence on fetal cerebral function (p > 0.05). Conclusion: The results showed that SGA infants have a poor continuity absence of SWC longer IBI lower maximum voltage and minimum voltage, which suggested that IUGR will resulted adverse influence on fetal cerebral function development to a degree. This work was supported by the Natural Science Foundation of China (81170577). http://dx.doi.org/10.1016/j.ijdevneu.2015.04.289
ISDN2014 0351 The impact of co-morbid seizure disorder on neuropsychological functioning in children and adolescents with FASD Sukhpreet Tamana 1,∗ , Gail Andrew 1 , James Reynolds 2 , Jacqueline Pei 1 , Carmen Rasmussen 1 1 2
University of Alberta, Canada Queens University, Canada
Introduction: Fetal Alcohol Spectrum Disorders (FASD) describes individuals with neuropsychological and behavioral impairments as a result of maternal alcohol consumption. FASD is associated with several co-morbidities including seizure disorder and epilepsy (Bell et al., 2010), which may have temporary or long-lasting structural and neuropsychological effects. However, it is unknown whether individuals with FASD, with and without seizure history, show different impairments in neuropsychological functions. Goal: to determine whether a seizure co-morbidity is associated with increased neuropsychological deficits in FASD. Method: Participants included 26 children and adolescents with FASD (11 with seizure history and 15 without) and 15 typically developing controls aged 7–16 years, which are a subset from the FASD NeuroDevNet project. Groups were matched on age and gender where possible. All children were assessed on selected subtests from the NEPSY-II that included measures of attention and executive functioning, memory, visual-spatial processing; a math test; as well as two parent rating scales measuring executive functioning (BRIEF) and adaptive behavior (ABAS-II). Results: As expected, the FASD group (with and without seizures) performed worse on most tests compared to controls. Importantly, participants with FASD and seizures performed significantly worse than those without seizures on a measure of inhibition. The FASD/seizure group also showed trends towards greater impairments than those without seizures in some areas involving more complex-inhibition and mathematics, but had similar performance in cognitive flexibility and attention. No group differences were found on the BRIEF and ABAS-II. Implications: These preliminary findings indicate that a seizure co-morbidity in FASD may have an increased effect on some neuropsychological domains, highlighting the critical need for more research in this area. These results also have implications for developing appropriate intervention strategies for individuals with FASD and seizure history. http://dx.doi.org/10.1016/j.ijdevneu.2015.04.290 ISDN2014 0352 Effects of prenatal alcohol exposure on social interaction in early and late adolescent male and female rats P.J. Holman ∗ , L.A. Hill, K. Wind, S. Haghighat, N. Mukhi, L. Takeuchi, G.L. Hammond, J. Weinberg Department of Cellular & Physiological Sciences, University of British Columbia, Vancouver, BC, Canada V6T 1Z3 Social behaviour deficits are a pervasive feature across Fetal Alcohol Spectrum Disorders (FASD). Animal models of prenatal alcohol exposure (PAE) have been useful in demonstrating social neurobehavioural deficits, however, more studies are needed to establish a distinctive social neurobehavioural profile that would distinguish FASD from other developmental disorders with social behaviour impairments, including autism spectrum disorder. Social
Abstracts / Int. J. Devl Neuroscience 47 (2015) 1–131
behaviour deficits emerge early and may become more pronounced around adolescence, a critical period of social behaviour development when the transition to a more complex social environment may exacerbate existing social behaviour impairments. Here, we tested social interaction without and with physical contact during adolescence using a well-established animal model of PAE. Pregnant rat dams were assigned to: 1) PAE: access to liquid ethanol diet ad libitum; 2) Pair-Fed: access to liquid control diet yoked to consumption of a PAE partner; or 3) Control: access to control diet ad libitum. Female and male offspring were tested prior to or following pubertal onset, first using a 2-chamber social interaction test in which one chamber was empty (Non-Social) and the other contained a social stimulus rat within a clear partition (Social). The following day, animals were placed in a testing apparatus and then introduced to a novel social stimulus. Social interaction behaviour without and with physical contact was filmed and later analyzed using video tracking and coding software. PAE animals did not differ from controls on the social interaction test without physical contact. However, results from the social interaction test with physical contact indicated PAE-related sexually dimorphic alterations in social behaviour, including increased olfactory investigation in females and increased pouncing in males. These results suggest that social motivation appears not to play a role in the social behaviour deficits following PAE; rather, PAE alters the normal expression of social behaviour in a sexually dimorphic fashion. Supported by NIH/NIAAA R37 AA007789 and R01 AA022460 and NeuroDevNet (Canadian NCE) to JW; PH is a NeuroDevNet Trainee. http://dx.doi.org/10.1016/j.ijdevneu.2015.04.291 ISDN2014 0353 N-cadherin promotes recruitment and migration of neural progenitor cells from the SVZ stem cell niche into demyelinated lesions Michael Klingener 1,2,∗ , Manideep Chavali 2 , Adan Aguirre 1,2 1
Program in Genetics, Stony Brook University, Stony Brook, NY 11794, USA 2 Department of Pharmacology, Stony Brook University, Stony Brook, NY 11794, USA Discrete cellular microenvironments regulate stem cell pools and their development, as well as function in maintaining tissue homeostasis. While the signaling elements modulating neural progenitor cells (NPCs) of the adult subventricular zone (SVZ) niche are fairly well understood, the pathways activated following injury, and the resulting outcomes, are less clear. In the present study, we used mouse models of demyelination and proteomics analysis to identify molecular cues present in the SVZ niche during injury, and analyzed their role on NPCs in the context of promoting myelin repair. Proteomic analysis of SVZ tissue from mice with experimental demyelination identified several proteins that are known to play roles in NPC proliferation, cell adhesion, and migration. Using the findings from this novel approach, we demonstrate a role for N-cadherin as a critical molecular element in promoting recovery following injury. Mechanistically, during the onset of demyelination in the subcortical white matter (SCWM), activation of epidermal growth factor receptor (EGFR) signaling in NPCs of the SVZ stimulates the interaction between N-cadherin and A Disintegrin And Metalloproteinase 10 (ADAM10). Upon cleavage and activation of N-cadherin signaling by ADAM10, NPCs undergo cytoskeletal rearrangement and polarization, enhancing their migration out of the SVZ into demyelinated lesions of the
107
SCWM. Genetically disrupting either EGFR signaling or ADAM10 inhibits this pathway, preventing N-cadherin regulated NPC polarization and migration. Additionally, in vivo experiments employing N-cadherin gain- and loss-of-function approaches demonstrate that N-cadherin enhances the recruitment of SVZ NPCs into demyelinated lesions and rescues the migration deficit observed in Nestin-CreTM /ADAM10fl/fl mice. Our data revealed that EGFRdependent N-cadherin signaling physically initiated by ADAM10 cleavage is a response of the pathological SVZ niche to promote repair of the injured brain. http://dx.doi.org/10.1016/j.ijdevneu.2015.04.292 ISDN2014 0354 The proliferation, lineage and regenerative potential of heterogeneous NG2+ glia cells in the adult cerebral cortex are regulated by continuous environmental cues Fikri Birey 1,2,∗ , Adan Aguirre 2 1
Graduate Program in Genetics, Stony Brook University, Stony Brook, NY 11794, USA 2 Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794, USA E-mail address: fi[email protected] (F. Birey). Abundantly found throughout the developing and mature CNS, NG2-expressing glia (NG2+ glia) are the most proliferative cell type in the CNS and are highly responsive to various kinds of brain injury. It has largely been assumed that NG2+ glia represent a homogenous cell population based on their proliferative and lineage capacities, both under physiological and pathological conditions. Yet, the full lineage and regenerative potential of NG2+ glia remain controversial in the adult cerebral cortex. To unravel cell-intrinsic abilities of NG2+ glia in the adult cerebral cortex, we developed a transgenic line to ablate NG2+ glia and examined the repopulation of NG2+ glia in situ after their massive depletion, therefore capturing the majority of these progenitors in their regenerative-like state as in during early CNS development. During the repopulation of the brain parenchyma, we observed two populations of NG2+ cells based in their proliferative dynamics; an active dividing and a quiescent NG2+ glia population. Interestingly, quiescent NG2+ cells that escape depletion are the principal cells that take charge to repopulate the depleted brain parenchyma. Furthermore, we show that the proliferation, repopulation and tile-like distribution characteristics of NG2+ glia is mediated by the netrin-1 signalling. NG2+ cells displayed a tri-potent lineage potential during this condition, hence generating along with NG2+ cells, oligodendrocytes and small but significant amount of neurons in the cortex. Finally, combining a mouse model of white matter injury and the NG2+ glia depletion system, we demonstrate increased efficiency in remyelination due to increased oligodendrocyte population. Our data demonstrate that the optimal distribution cues regulate heterogeneous NG2+ glia proliferative and lineage potentials in the adult cortex. http://dx.doi.org/10.1016/j.ijdevneu.2015.04.293