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1.
Background
The morphological development of neurons is a very complex process involving both genetic and environmental components. Mathematical modelling and numerical simulation are valuable tools in helping us unravel particular aspects of how individual neurons grow their characteristic morphologies and eventually form appropriate networks with each other.Methods
A variety of mathematical models that consider (1) neurite initiation (2) neurite elongation (3) axon pathfinding, and (4) neurite branching and dendritic shape formation are reviewed. The different mathematical techniques employed are also described.Results
Some comparison of modelling results with experimental data is made. A critique of different modelling techniques is given, leading to a proposal for a unified modelling environment for models of neuronal development.Conclusion
A unified mathematical and numerical simulation framework should lead to an expansion of work on models of neuronal development, as has occurred with compartmental models of neuronal electrical activity.2.
Background
Global cerebral ischemia triggers neurodegeneration in the hippocampal CA1 region, but the mechanism of neuronal death remains elusive. The epsilon isoform of protein kinase C (PKCε) has recently been identified as a master switch that controls the nucleocytoplasmic trafficking of ATF2 and the survival of melanoma cells. It is of interest to assess the role of PKCε–ATF2 signaling in neurodegeneration.Results
Phosphorylation of ATF2 at Thr-52 was reduced in the hippocampus of PKCε null mice, suggesting that ATF2 is a phosphorylation substrate of PKCε. PKCε protein concentrations were significantly reduced 4, 24, 48 and 72 h after transient global cerebral ischemia, resulting in translocation of nuclear ATF2 to the mitochondria. Degenerating neurons staining positively with Fluoro-Jade C exhibited cytoplasmic ATF2.Conclusions
Our results support the hypothesis that PKCε regulates phosphorylation and nuclear sequestration of ATF2 in hippocampal neurons during ischemia-induced neurodegeneration.3.
Background
Previous work suggested that macrophage migration inhibitory factor (MIF) may be involved in bladder inflammation. Therefore, the location of MIF was determined immunohistochemically in the bladder, prostate, major pelvic ganglia, sympathetic chain, the L6-S1 dorsal root ganglia (DRG) and the lumbosacral spinal cord of the rat.Results
In the pelvic organs, MIF immunostaining was prominent in the epithelia. MIF was widely present in neurons in the MPG and the sympathetic chain. Some of those neurons also co-localized tyrosine hydroxylase (TH). In the DRGs, some of the neurons that stained for MIF also stained for Substance P. In the lumbosacral spinal cord, MIF immunostaining was observed in the white mater, the dorsal horn, the intermediolateral region and in the area around the central canal. Many cells were intensely stained for MIF and glial fibrillary acidic protein (GFAP) suggesting they were glial cells. However, some cells in the lumbosacral dorsal horn were MIF positive, GFAP negative cells suggestive of neurons.Conclusions
Therefore, MIF, a pro-inflammatory cytokine, is localized to pelvic organs and also in neurons of the peripheral and central nervous tissues that innervate those organs. Changes in MIF's expression at the end organ and at peripheral and central nervous system sites suggest that MIF is involved in pelvic viscera inflammation and may act at several levels to promote inflammatory changes.4.
Purpose
To examine the effect of visual target blurring on accommodation.Methods
We evaluated the objective refraction values when the visual target (asterisk; 8°) was changed from the state without Gaussian blur (15 s) to the state with Gaussian blur adapted [0(without blur)?→?10, 0?→?50, 0?→?100: 15 s each].Results
In Gaussian blur 10, when blurring of the target occurred, refraction value did not change significantly. In Gaussian blur 50 and 100, when blurring of the target occurred, the refraction value became significantly myopic.Conclusion
Blurring of the distant visual target results in intervention of accommodation.5.
Laure?Verret Romain?Goutagny Patrice?Fort Laurène?Cagnon Denise?Salvert Lucienne?Léger Romuald?Boissard Paul?Salin Christelle?Peyron Pierre-Hervé?Luppi
Background
Peptidergic neurons containing the melanin-concentrating hormone (MCH) and the hypocretins (or orexins) are intermingled in the zona incerta, perifornical nucleus and lateral hypothalamic area. Both types of neurons have been implicated in the integrated regulation of energy homeostasis and body weight. Hypocretin neurons have also been involved in sleep-wake regulation and narcolepsy. We therefore sought to determine whether hypocretin and MCH neurons express Fos in association with enhanced paradoxical sleep (PS or REM sleep) during the rebound following PS deprivation. Next, we compared the effect of MCH and NaCl intracerebroventricular (ICV) administrations on sleep stage quantities to further determine whether MCH neurons play an active role in PS regulation.Results
Here we show that the MCH but not the hypocretin neurons are strongly active during PS, evidenced through combined hypocretin, MCH, and Fos immunostainings in three groups of rats (PS Control, PS Deprived and PS Recovery rats). Further, we show that ICV administration of MCH induces a dose-dependant increase in PS (up to 200%) and slow wave sleep (up to 70%) quantities.Conclusion
These results indicate that MCH is a powerful hypnogenic factor. MCH neurons might play a key role in the state of PS via their widespread projections in the central nervous system.6.
Background
We have developed a culture system for the efficient and directed differentiation of human embryonic stem cells (HESCs) to neural precursors and neurons.HESC were maintained by manual passaging and were differentiated to a morphologically distinct OCT-4+/SSEA-4- monolayer cell type prior to the derivation of embryoid bodies. Embryoid bodies were grown in suspension in serum free conditions, in the presence of 50% conditioned medium from the human hepatocarcinoma cell line HepG2 (MedII).Results
A neural precursor population was observed within HESC derived serum free embryoid bodies cultured in MedII conditioned medium, around 7–10 days after derivation. The neural precursors were organized into rosettes comprised of a central cavity surrounded by ring of cells, 4 to 8 cells in width. The central cells within rosettes were proliferating, as indicated by the presence of condensed mitotic chromosomes and by phosphoHistone H3 immunostaining. When plated and maintained in adherent culture, the rosettes of neural precursors were surrounded by large interwoven networks of neurites. Immunostaining demonstrated the expression of nestin in rosettes and associated non-neuronal cell types, and a radial expression of Map-2 in rosettes. Differentiated neurons expressed the markers Map-2 and Neurofilament H, and a subpopulation of the neurons expressed tyrosine hydroxylase, a marker for dopaminergic neurons.Conclusion
This novel directed differentiation approach led to the efficient derivation of neuronal cultures from HESCs, including the differentiation of tyrosine hydroxylase expressing neurons. HESC were morphologically differentiated to a monolayer OCT-4+ cell type, which was used to derive embryoid bodies directly into serum free conditions. Exposure to the MedII conditioned medium enhanced the derivation of neural precursors, the first example of the effect of this conditioned medium on HESC.7.
Takushi Kawamorita Kimiya Shimizu Rie Hoshikawa Kazutaka Kamiya Nobuyuki Shoji 《Optical Review》2018,25(3):336-339
Purpose
We investigated the relationship between central and peripheral corneal astigmatism in elderly patients.Methods
Seventy-six eyes of 76 elderly subjects (mean age?=?72.6?±?3.0 years) were included in the study. Corneal shape was evaluated using the Pentacam HR (Oculus, Wetzlark, Germany), which is comprised of a rotating Scheimpflug camera and a short-wavelength slit light. The power distribution map was selected and corneal astigmatism was calculated using front K-Readings in zones centered on the pupil. Analyzed zones were 2.0–6.0 mm in diameter.Results
Corneal astigmatism decreased as diameter increased, similar to what was observed in eyes with with-the-rule astigmatism and against-the-rule astigmatism (ANOVA, p?<?0.01). This effect was more pronounced in eyes with a large central corneal astigmatism (Spearman’s rank-correlation coefficient test, r?=?0.51, p?<?0.01). There was no change as to axis of corneal astigmatism (ANOVA, p?=?0.98).Conclusion
These results suggest that the relationship between central and peripheral corneal astigmatism should be taken into consideration to optimize vision when astigmatic correction is needed.8.
Background
Axon calibers vary widely among different animals, neuron classes, and even within the same neuron. What determines the diameter of axon branches?Results
We pursue the hypothesis that the axon caliber has evolved to minimize signal propagation delays, while keeping arbor volume to a minimum. For a general cost function, we show that the optimal diameters of mother and daughter branches at a bifurcation satisfy a power law. The derivation relies on the fact that the axon conduction speed scales as a power of axon diameter. Although available data are consistent with the law, there is a large spread in the data. Future experimental tests will determine whether this spread is due to biological variability or measurement error.Conclusions
Minimization of arbor volume and signal propagation delay may have been an important factor in the evolution of the brain.9.
Hung-Chen Wang Kuang-I Cheng Pei-Ru Chen Kuang-Yi Tseng Aij-Lie Kwan Lin-Li Chang 《BMC neuroscience》2018,19(1):72
Background
Glycine receptors (GlyRs) are involved in the development of spinal pain sensitization. The GlyRα3 subunit has recently emerged as a key factor in inflammatory pain pathways in the spinal cord dorsal horn (DH). Our study is to identify the extent of location and cell types expressing different GlyR subunits in spinal cord and dorsal root ganglion (DRGs). To tease out the possible actions of GlyRs on pain transmission, we investigate the effects produced by GlyRs on acute inflammatory pain by behavioral testing using prostaglandin E2 (PGE2) intrathecal injection models. Furthermore, we investigate the changes of GlyR expression in DRGs and spinal cord in rats after the induction of acute inflammatory pain.Results
Compared to the vehicle administration, the PGE2 intrathecal injection model produced significantly higher hyperalgesia, which started 3 h after PGE2 injection and lasted more than 5 h. PGE2 intrathecal injection significantly decreased GlyRα1 and GlyRα3 protein expressions in the L5 DH at 1 h and lasted to 5 h, and similar results were observed in the L5 DRG at 5 h. Confocal microscopic images showed the co-existence of punctate gephyrin and GlyRα3 immunoreactivity (IR) throughout the gray matter of the spinal cord, mainly in DH laminae I–III neurons and in ventral horn neurons. It also showed the co-existence of punctate gephyrin and GlyRα3 IR in DRG neurons.Conclusions
In this study, PGE2 intrathecal injection significantly decreased protein expression of gephyrin, GlyRα1 and GlyRα3 in spinal cord DH and DRG. The gephyrin and GlyRα3 were localized on neuron cells both in the DH and DRG.10.
Purpose
To evaluate the relationship between corneal and ocular higher order wavefront aberrations (HOAs) and age in young subjects aged 20 years or less.Methods
Corneal and ocular HOAs of the right eyes of 87 normal subjects were measured using videokeratography and the Hartmann–Shack wavefront aberrometer (KR-9000PW; Topcon Corp., Tokyo, Japan). The HOAs were calculated using Zernike polynomials up to the sixth order. From the Zernike coefficients, the root mean squares (RMS) of coma and spherical aberration were calculated.Results
Corneal spherical-like aberrations significantly correlated with age (r = 0.420, p < 0.001); however, coma-like aberrations and total HOAs did not significantly correlate with age. None of the ocular HOAs significantly correlated with age. In addition, a gender-wise comparison of the collected data showed that corneal and ocular HOAs did not significantly correlate with age.Conclusion
In children, the corneal and ocular total HOAs did not vary with age. Compared to the previous reports in adults, we found fewer corneal and ocular HOAs in children.11.
Background
To determine whether early imitative responses fade out following the maturation of attentional mechanisms, the relationship between primitive imitation behaviors and the development of attention was examined in 4-month-old infants. They were divided into high and low imitators, based on an index of imitation. The status of attention was assessed by studying inhibition of return (IOR). Nine-month-old infants were also tested to confirm the hypothesis.Results
The IOR latency data replicate previous results that infants get faster to produce a covert shift of attention with increasing age. However, those 4-month-olds who showed less imitation had more rapid saccades to the cue before target presentation.Conclusion
The cortical control of saccade planning appears to be related to an apparent drop in early imitation. We interpret the results as suggesting a relationship between the status of imitation and the neural development of attention-related eye movement.12.
Background
The mitogen-activated protein kinases (MAPKs) have been shown to participate in a wide array of cellular functions. A role for some MAPKs (e.g., extracellular signal-regulated kinase, Erk1/2) has been documented in response to certain physiological stimuli, such as ischemia, visceral pain and electroconvulsive shock. We recently demonstrated that restraint stress activates the Erk MAPK pathway, but not c-Jun-N-terminal kinase/stress-activated protein kinase (JNK/SAPK) or p38MAPK, in several rat brain regions. In the present study, we investigated the effects of a different stressor, acute forced swim stress, on the phosphorylation (P) state of these MAPKs in the hippocampus, neocortex, prefrontal cortex, amygdala and striatum. In addition, effects on the phosphorylation state of the upstream activators of the MAPKs, their respective MAPK kinases (MAPKKs; P-MEK1/2, P-MKK4 and P-MKK3/6), were determined. Finally, because the Erk pathway can activate c-AMP response element (CRE) binding (CREB) protein, and swim stress has recently been reported to enhance CREB phosphorylation, changes in P-CREB were also examined.Results
A single 15 min session of forced swimming increased P-Erk2 levels 2–3-fold in the neocortex, prefrontal cortex and striatum, but not in the hippocampus or amygdala. P-JNK levels (P-JNK1 and/or P-JNK2/3) were increased in all brain regions about 2–5-fold, whereas P-p38MAPK levels remained essentially unchanged. Surprisingly, levels of the phosphorylated MAPKKs, P-MEK1/2 and P-MKK4 (activators of the Erk and JNK pathways, respectively) were increased in all five brain regions, and much more dramatically (P-MEK1/2, 4.5 to > 100-fold; P-MKK4, 12 to ~300-fold). Consistent with the lack of forced swim on phosphorylation of p38MAPK, there appeared to be no change in levels of its activator, P-MKK3/6. P-CREB was increased in all but cortical (prefrontal, neocortex) areas.Conclusions
Swim stress specifically and markedly enhanced the phosphorylation of the MAPKKs P-MEK1/2 and P-MKK4 in all brain regions tested without apparent alteration in the phosphorylation of P-MKK3/6. Curiously, phosphorylation of their cognate substrates (Erk and JNK) was increased to a much more modest extent, and in some brain regions was not altered. Similarly, there was a region-specific discrepancy between Erk and CREB phosphorylation. Possible explanations for these findings and comparison with the effects of restraint stress will be discussed.13.
Background
How does the brain repair obliterated speech and cope with acoustically ambivalent situations? A widely discussed possibility is to use top-down information for solving the ambiguity problem. In the case of speech, this may lead to a match of bottom-up sensory input with lexical expectations resulting in resonant states which are reflected in the induced gamma-band activity (GBA).Methods
In the present EEG study, we compared the subject's pre-attentive GBA responses to obliterated speech segments presented after a series of correct words. The words were a minimal pair in German and differed with respect to the degree of specificity of segmental phonological information.Results
The induced GBA was larger when the expected lexical information was phonologically fully specified compared to the underspecified condition. Thus, the degree of specificity of phonological information in the mental lexicon correlates with the intensity of the matching process of bottom-up sensory input with lexical information.Conclusions
These results together with those of a behavioural control experiment support the notion of multi-level mechanisms involved in the repair of deficient speech. The delineated alignment of pre-existing knowledge with sensory input is in accordance with recent ideas about the role of internal forward models in speech perception.14.
Background
To learn, a motor system needs to know its sensitivity derivatives, which quantify how its neural commands affect motor error. But are these derivatives themselves learned, or are they known solely innately? Here we test a recent theory that the brain's estimates of sensitivity derivatives are revisable based on sensory feedback. In its simplest form, the theory says that each control system has a single, adjustable estimate of its sensitivity derivatives which affects all aspects of its task, e.g. if you learn to reach to mirror-reversed targets then your revised estimate should reverse not only your initial aiming but also your online course adjustments when the target jumps in mid-movement.Methods
Human subjects bent a joystick to move a cursor to a target on a computer screen, but the cursor's motion was reversed relative to the joystick's. The target jumped once during each movement. Subjects had up to 4000 trials to practice aiming and responding to target jumps.Results
All subjects learned to reverse both initial aiming and course adjustments.Conclusions
Our study confirms that sensitivity derivatives can be relearned. It is consistent with the idea of a single, all-purpose estimate of those derivatives; and it suggests that the estimate is a function of context, as one would expect given that the true sensitivity derivatives may vary with the state of the controlled system, the target, and the motor commands.15.
Background
While it is well known that bradykinin B2 agonists increase plasma protein extravasation (PPE) in brain tumors, the bradykinin B1 agonists tested thus far are unable to produce this effect. Here we examine the effect of the selective B1 agonist bradykinin (BK) Sar-[D-Phe8]des-Arg9BK (SAR), a compound resistant to enzymatic degradation with prolonged activity on PPE in the blood circulation in the C6 rat glioma model.Results
SAR administration significantly enhanced PPE in C6 rat brain glioma compared to saline or BK (p < 0.01). Pre-administration of the bradykinin B1 antagonist [Leu8]-des-Arg (100 nmol/Kg) blocked the SAR-induced PPE in the tumor area.Conclusions
Our data suggest that the B1 receptor modulates PPE in the blood tumor barrier of C6 glioma. A possible role for the use of SAR in the chemotherapy of gliomas deserves further study.16.
Sheng Wei Meng Ren Jieqiong Wang Jie Gao Yinghui Guo Kaiyong Xu Fang Li Dehao Zhu Hao Zhang Rongju Lv Mingqi Qiao 《BMC neuroscience》2018,19(1):61
Background
Epidemiological surveys and studies with animal models have established a relationship between maternal stress and affective disorders in their offspring. However, whether maternal depression before pregnancy influences behaviour and related neurobiological mechanisms in the offspring has not been studied.Results
A social defeat stress (SDS) maternal rat model was established using the resident-intruder paradigm with female specific pathogen-free Wistar rats and evaluated with behavioural tests. SDS maternal rats showed a significant reduction in sucrose preference and locomotor and exploratory activities after 4 weeks of stress. In the third week of the experiment, a reduction in body weight gain was observed in SDS animals. Sucrose preference, open field, the elevated-plus maze, light–dark box, object recognition, the Morris water maze, and forced swimming tests were performed using the 2-month-old male offspring of the female SDS rats. Offspring subjected to pre-gestational SDS displayed enhanced anxiety-like behaviours, reduced exploratory behaviours, reduced sucrose preference, and atypical despair behaviours. With regard to cognition, the offspring showed significant impairments in the retention phase of the object recognition test, but no effect was observed in the acquisition phase. These animals also showed impairments in recognition memory, as the discrimination index in the Morris water maze test in this group was significantly lower for both 1 h and 24 h memory retention compared to controls. Corticosterone, adrenocorticotropic hormone, and monoamine neurotransmitters levels were determined using enzyme immunoassays or radioimmunoassays in plasma, hypothalamus, left hippocampus, and left prefrontal cortex samples from the offspring of the SDS rats. These markers of hypothalamic–pituitary–adrenal axis responsiveness and the monoaminergic system were significantly altered in pre-gestationally stressed offspring. Brain-derived neurotrophic factor (BDNF), cyclic adenosine monophosphate response element binding protein (CREB), phosphorylated CREB (pCREB), and serotonin transporter (SERT) protein levels were evaluated using western blotting with right hippocampus and right prefrontal cortex samples. Expression levels of BDNF, pCREB, and SERT in the offspring were also altered in the hippocampus and in the prefrontal cortex; however, there was no effect on CREB.Conclusion
We conclude that SDS before pregnancy might induce depressive-like behaviours, cognitive deficits, and neurobiological alterations in the offspring.17.
Marie-Laure Beaud Eric Schmidlin Thierry Wannier Patrick Freund Jocelyne Bloch Anis Mir Martin E Schwab Eric M Rouiller 《BMC neuroscience》2008,9(1):5
Background
After unilateral cervical cord lesion at the C7/C8 border interrupting the dorsolateral funiculus in adult monkeys, neutralization of Nogo-A using a specific monoclonal antibody promoted sprouting of corticospinal (CS) axons rostral and caudal to the lesion and, in parallel, improved functional recovery. In monkeys lesioned but not treated with the anti-Nogo-A antibody, the CS neurons in the contralesional primary motor cortex (M1) survived to the axotomy, but their soma shrank. Because the anti-Nogo-A treatment induces regeneration and/or sprouting of CS axons, it may improve access to neurotrophic factors. The question therefore arises as to whether anti-Nogo-A treatment prevents the soma shrinkage observed in the contralesional M1?Results
Using the marker SMI-32, a quantitative and qualitative anatomical assessment of the pyramidal neurons in the layer V (thus including the CS cells) in M1 was performed and compared across three groups of animals: intact monkeys (n = 5); monkeys subjected to the cervical cord lesion and treated with a control antibody (n = 4); monkeys with the cervical lesion and treated with anti-Nogo-A antibody (n = 5). SMI-32 positive neurons on the side contralateral to the lesion were generally less well stained than those on the ipsilesional hemisphere, suggesting that they expressed less neurofilaments. Nevertheless, in all three groups of monkeys, the amount of SMI-32 positive neurons in both hemispheres was generally comparable, confirming the notion that most axotomized CS neurons survived. However, shrinkage of CS cell body area was observed in the contralesional hemisphere in the two groups of lesioned monkeys. The cell surface shrinkage was found to be of the same magnitude in the monkeys treated with the anti-Nogo-A antibody as in the control antibody treated monkeys.Conclusion
The anti-Nogo-A antibody treatment did not preserve the axotomized CS cells from soma shrinkage, indicating that the anti-Nogo-A antibody treatment affects morphologically the axotomized CS neurons mainly at distal levels, especially the axon collateralization in the cervical cord, and little or not at all at the level of their soma.18.
Background
How do listeners manage to recognize words in an unfamiliar language? The physical continuity of the signal, in which real silent pauses between words are lacking, makes it a difficult task. However, there are multiple cues that can be exploited to localize word boundaries and to segment the acoustic signal. In the present study, word-stress was manipulated with statistical information and placed in different syllables within trisyllabic nonsense words to explore the result of the combination of the cues in an online word segmentation task.Results
The behavioral results showed that words were segmented better when stress was placed on the final syllables than when it was placed on the middle or first syllable. The electrophysiological results showed an increase in the amplitude of the P2 component, which seemed to be sensitive to word-stress and its location within words.Conclusion
The results demonstrated that listeners can integrate specific prosodic and distributional cues when segmenting speech. An ERP component related to word-stress cues was identified: stressed syllables elicited larger amplitudes in the P2 component than unstressed ones.19.