scholarly journals Perinatal Exposure of Bisphenol A Differently Affects Dendritic Spines of Male and Female Grown-Up Adult Hippocampal Neurons

2021 ◽  
Vol 15 ◽  
Author(s):  
Suguru Kawato ◽  
Mari Ogiue-Ikeda ◽  
Mika Soma ◽  
Hinako Yoshino ◽  
Toshihiro Kominami ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Estrous Cycle ◽  
Dendritic Spines ◽  
Hippocampal Neurons ◽  
Lucifer Yellow ◽  
Hippocampal Slices ◽  
Perinatal Exposure ◽  
Spine Density ◽  
Large Head ◽  
Moderate Change

Perinatal exposure to Bisphenol A (BPA) at a very low dose may modulate the development of synapses of the hippocampus during growth to adulthood. Here, we demonstrate that perinatal exposure to 30 μg BPA/kg per mother’s body weight/day significantly altered the dendritic spines of the grownup rat hippocampus. The density of the spine was analyzed by imaging of Lucifer Yellow-injected CA1 glutamatergic neurons in adult hippocampal slices. In offspring 3-month male hippocampus, the total spine density was significantly decreased by BPA exposure from 2.26 spines/μm (control, no BPA exposure) to 1.96 spines/μm (BPA exposure). BPA exposure considerably changed the normal 4-day estrous cycle of offspring 3-month females, resulting in a 4∼5 day estrous cycle with 2-day estrus stages in most of the subjects. In the offspring 3-month female hippocampus, the total spine density was significantly increased by BPA exposure at estrus stage from 2.04 spines/μm (control) to 2.25 spines/μm (BPA exposure). On the other hand, the total spine density at the proestrus stage was moderately decreased from 2.33 spines/μm (control) to 2.19 spines/μm (BPA exposure). Thus, after the perinatal exposure to BPA, the total spine density in males became lower than that in females. Concerning the BPA effect on the morphology of spines, the large-head spine was significantly changed with its significant decrease in males and moderate change in females.

scholarly journals CREB Activation Mediates Plasticity in Cultured Hippocampal Neurons

1998 ◽  
Vol 6 (3) ◽  
pp. 1-7 ◽  
Author(s):  
Menahem Segal ◽  
Diane D. Murphy
Keyword(s):  
Cyclic Amp ◽  
Dendritic Spines ◽  
Hippocampal Neurons ◽  
Long Term Potentiation ◽  
Spine Density ◽  
Creb Phosphorylation ◽  
Molecular Events ◽  
Term Potentiation ◽  
Element Binding Protein ◽  
Responsive Element

Activation of cyclic AMP dependent kinase is believed to mediate slow onset, long-term potentiation (LTP) in central neurons. Cyclic- AMP activates a cascade of molecular events leading to phosphorylation of the nuclear cAMP responsive element binding protein (pCREB). Whereas a variety of stimuli lead to activation of CREB, the molecular processes downstream of CREB, which may be relevant to neuronal plasticity, are yet largely unknown. We have recently found that following exposure to estradiol, pCREB mediates the large increase in dendritic spine density in cultured rat hippocampal neurons. We now extend these observations to include other stimuli, such as bicuculline, that cause the formation of new dendritic spines. Such stimuli share with estradiol the same mechanism of action in that both require activity-dependent CREB phosphorylation. Our observations suggest that CREB phosphorylation is a necessary, but perhaps not sufficient, step in the process leading to the generation of new dendritic spines and perhaps to functional plasticity as well.

Rapid Effects of Estradiol on Dendritic Spines and Synaptic Plasticity in the Male and Female Hippocampus

2020 ◽  
pp. 38-47
Author(s):  
Asami Kato ◽  
Gen Murakami ◽  
Yasushi Hojo ◽  
Sigeo Horie ◽  
Suguru Kawato
Keyword(s):  
Synaptic Plasticity ◽  
Dendritic Spine ◽  
Hippocampal Neurons ◽  
Molecular Mechanisms ◽  
Hippocampal Slices ◽  
Spine Density ◽  
Male And Female ◽  
Dendritic Spine Density ◽  
Male And Female Rats ◽  
Rapid Modulation

Although the potent estrogen, 17β‎-estradiol (E2), has long been known to regulate the hippocampal dendritic spine density and synaptic plasticity, the molecular mechanisms through which it does so are less well understood. This chapter discusses the rapid modulation of hippocampal dendritic spine density and synaptic plasticity in male and female rats, with particular attention to studies in hippocampal slices from male rats. Among the mechanisms described are the roles of specific cell-signaling kinases and estrogen receptors in mediating the effects of E2 and progesterone on hippocampal neurons. In addition, dynamic changes of spine structures over time and sex differences in spine regulation are also considered. Finally, the chapter ends by discussing the importance of local hippocampal synthesis of E2 and androgens to hippocampal spine morphology and plasticity.

scholarly journals Hippocampal spine changes across the sleep–wake cycle: corticosterone and kinases

2015 ◽  
Vol 226 (2) ◽  
pp. M13-M27 ◽  
Author(s):  
Muneki Ikeda ◽  
Yasushi Hojo ◽  
Yoshimasa Komatsuzaki ◽  
Masahiro Okamoto ◽  
Asami Kato ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Glucocorticoid Receptors ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Spine Density ◽  
Sleep State ◽  
Ca1 Pyramidal Neurons ◽  
Dendritic Spine Density ◽  
Large Head ◽  
Living State

The corticosterone (CORT) level changes along the circadian rhythm. Hippocampus is sensitive to CORT, since glucocorticoid receptors are highly expressed. In rat hippocampus fixed in a living state every 3 h, we found that the dendritic spine density of CA1 pyramidal neurons increased upon waking (within 3 h), as compared with the spine density in the sleep state. Particularly, the large-head spines increased. The observed change in the spine density may be due to the change in the hippocampal CORT level, since the CORT level at awake state (∼30 nM) in cerebrospinal fluid was higher than that at sleep state (∼3 nM), as observed from our earlier study. In adrenalectomized (ADX) rats, such a wake-induced increase of the spine density disappeared. S.c. administration of CORT into ADX rats rescued the decreased spine density. By using isolated hippocampal slices, we found that the application of 30 nM CORT increased the spine density within 1 h and that the spine increase was mediated via PKA, PKC, ERK MAPK, and LIMK signaling pathways. These findings suggest that the moderately rapid increase of the spine density on waking might mainly be caused by the CORT-driven kinase networks.

scholarly journals A Human-Specific Schizophrenia Risk Tandem Repeat Affects Alternative Splicing of a Human-Unique Isoform AS3MTd2d3 and Mushroom Dendritic Spine Density

2020 ◽  
Author(s):  
Xin Cai ◽  
Zhi-Hui Yang ◽  
Hui-Juan Li ◽  
Xiao Xiao ◽  
Ming Li ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Tandem Repeat ◽  
Dendritic Spines ◽  
Hippocampal Neurons ◽  
Variable Number ◽  
High Linkage Disequilibrium ◽  
Spine Density ◽  
Functional Variation ◽  
Human Specific

Abstract Recent advances in functional genomics have facilitated the identification of multiple genes and isoforms associated with the genetic risk of schizophrenia, yet the causal variations remain largely unclear. A previous study reported that the schizophrenia risk single-nucleotide polymorphism (SNP) rs7085104 at 10q24.32 was in high linkage disequilibrium (LD) with a human-specific variable number of tandem repeat (VNTR), and both were significantly associated with the brain mRNA expression of a human-unique AS3MTd2d3 isoform in Europeans and African Americans. In this study, we have shown the direct regulation of the AS3MTd2d3 mRNA expression by this VNTR through an in vitro minigene splicing assay, suggesting that it is likely a causative functional variation. Intriguingly, we have further confirmed that the VNTR and rs7085104 are significantly associated with AS3MTd2d3 mRNA expression in brains of Han Chinese donors, and rs7085104 is also associated with risk of schizophrenia in East Asians. Finally, the overexpression of AS3MTd2d3 in cultured primary hippocampal neurons results in significantly reduced densities of mushroom dendritic spines, implicating its potential functional impact. Considering the crucial roles of dendritic spines in neuroplasticity, these results reveal the potential regulatory impact of the schizophrenia risk VNTR on AS3MTd2d3 and provide insights into the underlying biological mechanisms.

K-Cl Cotransporter 2–mediated Cl− Extrusion Determines Developmental Stage–dependent Impact of Propofol Anesthesia on Dendritic Spines

2017 ◽  
Vol 126 (5) ◽  
pp. 855-867 ◽  
Author(s):  
Martin Puskarjov ◽  
Hubert Fiumelli ◽  
Adrian Briner ◽  
Timea Bodogan ◽  
Kornel Demeter ◽  
...  
Keyword(s):  
Dendritic Spines ◽  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Lucifer Yellow ◽  
Spine Density ◽  
General Anesthetics ◽  
Early Postnatal Development ◽  
Age Dependent ◽  
Opposite Action ◽  
Rat Somatosensory Cortex

Abstract Background General anesthetics potentiating γ-aminobutyric acid (GABA)–mediated signaling are known to induce a persistent decrement in excitatory synapse number in the cerebral cortex when applied during early postnatal development, while an opposite action is produced at later stages. Here, the authors test the hypothesis that the effect of general anesthetics on synaptogenesis depends upon the efficacy of GABA receptor type A (GABAA)–mediated inhibition controlled by the developmental up-regulation of the potassium-chloride (K-Cl) cotransporter 2 (KCC2). Methods In utero electroporation of KCC2 was used to prematurely increase the efficacy of (GABAA)–mediated inhibition in layer 2/3 pyramidal neurons in the immature rat somatosensory cortex. Parallel experiments with expression of the inward-rectifier potassium channel Kir2.1 were done to reduce intrinsic neuronal excitability. The effects of these genetic manipulations (n = 3 to 4 animals per experimental group) were evaluated using iontophoretic injection of Lucifer Yellow (n = 8 to 12 cells per animal). The total number of spines analyzed per group ranged between 907 and 3,371. Results The authors found a robust effect of the developmental up-regulation of KCC2–mediated Cl− transport on the age-dependent action of propofol on dendritic spines. Premature expression of KCC2, unlike expression of a transport-inactive KCC2 variant, prevented a propofol-induced decrease in spine density. In line with a reduction in neuronal excitability, the above result was qualitatively replicated by overexpression of Kir2.1. Conclusions The KCC2–dependent developmental increase in the efficacy of GABAA–mediated inhibition is a major determinant of the age-dependent actions of propofol on dendritic spinogenesis.

Nanomolar dose of bisphenol A rapidly modulates spinogenesis in adult hippocampal neurons

2012 ◽  
Vol 351 (2) ◽  
pp. 317-325 ◽  
Author(s):  
Nobuaki Tanabe ◽  
Hinako Yoshino ◽  
Tetsuya Kimoto ◽  
Yasushi Hojo ◽  
Mari Ogiue-Ikeda ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Hippocampal Neurons

scholarly journals Zinc Enhances the Inhibitory Effects of Strychnine-Sensitive Glycine Receptors in Mouse Hippocampal Neurons

2007 ◽  
Vol 98 (6) ◽  
pp. 3666-3676 ◽  
Author(s):  
Hai Xia Zhang ◽  
Liu Lin Thio
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Hippocampal Neurons ◽  
Neuronal Excitability ◽  
Hippocampal Slices ◽  
Glycine Receptors ◽  
Inhibitory Effects ◽  
Action Potential Firing ◽  
Embryonic Mouse ◽  
Potential Firing

Although extracellular Zn2+ is an endogenous biphasic modulator of strychnine-sensitive glycine receptors (GlyRs), the physiological significance of this modulation remains poorly understood. Zn2+ modulation of GlyR may be especially important in the hippocampus where presynaptic Zn2+ is abundant. Using cultured embryonic mouse hippocampal neurons, we examined whether 1 μM Zn2+, a potentiating concentration, enhances the inhibitory effects of GlyRs activated by sustained glycine applications. Sustained 20 μM glycine (EC25) applications alone did not decrease the number of action potentials evoked by depolarizing steps, but they did in 1 μM Zn2+. At least part of this effect resulted from Zn2+ enhancing the GlyR-induced decrease in input resistance. Sustained 20 μM glycine applications alone did not alter neuronal bursting, a form of hyperexcitability induced by omitting extracellular Mg2+. However, sustained 20 μM glycine applications depressed neuronal bursting in 1 μM Zn2+. Zn2+ did not enhance the inhibitory effects of sustained 60 μM glycine (EC70) applications in these paradigms. These results suggest that tonic GlyR activation could decrease neuronal excitability. To test this possibility, we examined the effect of the GlyR antagonist strychnine and the Zn2+ chelator tricine on action potential firing by CA1 pyramidal neurons in mouse hippocampal slices. Co-applying strychnine and tricine slightly but significantly increased the number of action potentials fired during a depolarizing current step and decreased the rheobase for action potential firing. Thus Zn2+ may modulate neuronal excitability normally and in pathological conditions such as seizures by potentiating GlyRs tonically activated by low agonist concentrations.

Developmental study of benzodiazepine effects on monosynaptic GABAA-mediated IPSPs of rat hippocampal neurons

1993 ◽  
Vol 70 (3) ◽  
pp. 1076-1085 ◽  
Author(s):  
C. Rovira ◽  
Y. Ben-Ari
Keyword(s):  
Hippocampal Neurons ◽  
Receptor Agonist ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Developmental Study ◽  
Type I ◽  
Gamma Aminobutyric Acid ◽  
Adult Rats ◽  
Young Rats ◽  
In Cells

1. The effects of type I (BZ1) and type II (BZ2) benzodiazepine receptor ligands on monosynaptic gamma-aminobutyric acid (GABA)A-mediated inhibitory postsynaptic potentials (IPSPs) and on responses to exogenously applied GABA were studied using intracellular recordings from CA3 pyramidal cells of rat hippocampal slices taken at different postnatal stages [postnatal day 4 (P4)-P35)]. 2. The effects of midazolam, a BZ1 and BZ2 receptor agonist, were tested on the monosynaptic IPSPs at different stages. Monosynaptic, bicuculline-sensitive IPSPs were evoked by hilar stimulation in presence of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) antagonists [6-cyano-7-nitroquinoxaline-2,3-dione (10 microM) and D(-)2-amino-5-phosphonopentanoic acid (50 microM)]. Midazolam at 300 nM maximally increased the duration and amplitude of monosynaptic GABAA-mediated IPSPs in neurons from pups (P4-P6, n = 6) and young (P7-P12, n = 8) and adult (P25-P35, n = 9) rats. All the effects of midazolam on IPSPs were reversed by the antagonist Ro 15-1788 (10 microM). 3. The effect of midazolam was also tested on the response to exogenously applied GABA (5 mM) in the presence of tetrodotoxine [TTX (1 microM)]. In neurons from young rats (n = 9), midazolam (1 nM-1 microM) did not change the responses to exogenously applied GABA, whereas in adult rats (n = 8) midazolam maximally increased GABA currents at 30 nM. 4. The effect of zolpidem, a BZ1 receptor agonist, was tested on monosynaptic IPSPs and GABA currents at different stages. Zolpidem (10 nM-1 microM) was inactive in cells from young rats (n = 12). In neurons from adult rats, zolpidem maximally increased the duration and amplitude of the monosynaptic IPSPs at 300 nM (n = 5) and the amplitude of GABA current at 30-100 nM (n = 5). 5. Methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) (300 nM), an inverse agonist of BZ1 and BZ2 receptors, decreased the amplitude and duration of monosynaptic IPSPs in neurons from pups (n = 3) and young (n = 4) and adult (n = 5) rats. In all cases, full recovery was obtained after exposure to R0 15-1788 (10 microM). DMCM (300 nM-10 microM) failed to reduce GABA responses in cells from young (n = 3) or adult (n = 7) rats. 6. Results indicate that the regulation by benzodiazepine of GABAA-mediated IPSPs varies with the developmental stage.(ABSTRACT TRUNCATED AT 400 WORDS)

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