Andrea De Giorgio

Early Exposure to Alcohol Leads to Permanent Impairment of Dendritic Excitability in Neocortical Pyramidal Neurons

Exposure to alcohol in utero is a well known cause of mental retardation in humans. Using experimental models of fetal alcohol spectrum disorder, it has been demonstrated that cortical pyramidal neurons and their projections are profoundly and permanently impaired. Yet, how the functional features of these cells are modified and how such modifications impact cognitive processes is still unknown. To address this, we studied the intrinsic electrophysiological properties of pyramidal neurons in young adult rats (P30–P60) exposed to ethanol inhalation during the first week of postnatal life (P2–P6). Dual whole-cell recordings from the soma and distal apical dendrites were performed and, following the injection of depolarizing current into the dendrites, layer 5 neurons from ethanol-treated (Et) animals displayed a lower number and a shorter duration of dendritic spikes, attributable to a downregulation of calcium electrogenesis. As a consequence, the mean number of action potentials recorded at the soma after dendritic current injection was also lower in Et animals. No significant differences between Et and controls were observed in the firing pattern elicited in layer 5 neurons by steps of depolarizing somatic current, even though the firing rate was significantly lower in Et animals. The firing pattern and the firing rate of layer 2/3 neurons were not affected by alcohol exposure.

Long-term alterations of striatal parvalbumin interneurons in a rat model of early exposure to alcohol

BackgroundExposure to alcohol in utero is a known cause of mental retardation. Although a certain degree of motor impairment is always associated with fetal alcohol spectrum disorder, little is known about the neurobiological basis of the defective motor control. We have studied the striatal interneurons containing parvalbumin in a rat model of fetal alcohol spectrum disorder.MethodsNewborn rats received ethanol by inhalation from postnatal day two through six and parvalbumin striatal neurons were labeled by immunohistochemistry on postnatal day 60. The spatial distribution of parvalbumin interneurons was studied using Voronoi spatial tessellation and their dendritic trees were completely reconstructed.ResultsParvalbumin interneurons of ethanol-treated animals showed a clustered spatial distribution similar to that observed in control animals. The dendritic tree of parvalbumin interneurons was significantly reduced in ethanol-treated animals, as compared with controls.ConclusionsStriatal parvalbumin interneurons are crucial components of the brain network serving motor control. Therefore, the shrinkage of their dendrites could contribute to the motor and cognitive symptoms observed in fetal alcohol spectrum disorder.Exposure to alcohol in utero is a known cause of mental retardation. Although a certain degree of motor impairment is always associated with fetal alcohol spectrum disorder, little is known about the neurobiological basis of the defective motor control. We have studied the striatal interneurons containing parvalbumin in a rat model of fetal alcohol spectrum disorder. Newborn rats received ethanol by inhalation from postnatal day two through six and parvalbumin striatal neurons were labeled by immunohistochemistry on postnatal day 60. The spatial distribution of parvalbumin interneurons was studied using Voronoi spatial tessellation and their dendritic trees were completely reconstructed. Parvalbumin interneurons of ethanol-treated animals showed a clustered spatial distribution similar to that observed in control animals. The dendritic tree of parvalbumin interneurons was significantly reduced in ethanol-treated animals, as compared with controls. Striatal parvalbumin interneurons are crucial components of the brain network serving motor control. Therefore, the shrinkage of their dendrites could contribute to the motor and cognitive symptoms observed in fetal alcohol spectrum disorder.

Reduced density of dendritic spines in pyramidal neurons of rats exposed to alcohol during early postnatal life

Dendritic spines are the main postsynaptic sites of excitatory connections of neocortical pyramidal neurons. Alterations of spine shape, number, and density can be observed in different mental diseases, including those caused by developmental alcohol exposure. Pyramidal neurons of layer 2/3 are the most abundant cells of the neocortex and represent the main source of associative cortico‐cortical connections. These neurons are essential for higher functions mediated by the cortex such as feature selection and perceptual grouping. Furthermore, their connections have been shown to be altered in experimental models of fetal alcohol spectrum disorders.

Selective underexpression of Kv3.2 and Kv3.4 channels in the cortex of rats exposed to ethanol during early postnatal life

The expression of voltage-gated potassium channels belonging to the Kv3 family has been studied in the sensori-motor cortex of rats exposed to alcohol inhalation during the first postnatal week (P2–P6). The study was carried out using comparative RT-PCR. At P9, a significant reduction of the expression of Kv3.2 and Kv3.4 subunits occurred in alcohol-treated animals, as compared with controls. The expression of the Kv3.4a splicing variant, which is thought to be critically involved in the high-frequency firing of some cortical interneurons, was also correspondingly reduced. The downregulation of Kv3.2 and Kv3.4a subunits represented a long-lasting effect of alcohol exposure, since it was also observed in P24 animals. The expression of both Kv3.1 and Kv3.3 channels appeared to be not significantly affected by alcohol exposure. An increased susceptibility to apoptotic neuronal death after early postnatal exposure to ethanol was confirmed by the lower bcl-2/bax ratio observed in alcohol-treated animals. Although Kv3.4 subunits are thought to trigger apoptosis, the lack of upregulation in our model argues against their involvement in the mechanism leading to alcohol-induced apoptosis. The possible consequences of the selective downregulation of Kv3 subunits on the cortical function, as well as their relevance for the genesis of fetal alcohol effects, are discussed.

Alterations of neocortical pyramidal neurons: turning points in the genesis of mental retardation

Pyramidal neurons (PNs) represent the majority of neocortical cells and their involvement in cognitive functions is decisive. Therefore, they are the most obvious target of developmental disorders characterized by mental retardation. Genetic and non-genetic forms of intellectual disability share a few basic pathogenetic signatures that result in the anomalous function of PNs. Here, we review the key mechanisms impairing these neurons and their participation in the cortical network, with special focus on experimental models of fetal exposure to alcohol. Due to the heterogeneity of PNs, some alterations affect selectively a given cell population, which may also differ depending on the considered pathology. These specific features open new possibilities for the interpretation of cognitive defects observed in mental retardation syndromes, as well as for novel therapeutic interventions.

I performed experiments and I have results. Wow, and now?

Writing a scientific article is not an easy task, but it is definitely a great satisfaction to be able to conclude and publish it. Indeed, each publication is a service we make to the entire scientific community and to the advancement of science even before our personal career. There is and there will not be a final book/article for writing a scientific paper. Therefore, some knowledge is a decisive factor to increase the chances of our work being accepted by a specialized scientific journal. The purpose of this editorial is to trace an ideal path, based on our personal experience, useful to properly structure a scientific article, from bibliographic research to cover letter. Articles should not be written in a polished way to gratify ones own ego, but they must be written for anyone who can read and understand them. Level of evidence V.

Enhancing motor learning of young soccer players through preventing an internal focus of attention: The effect of shoes colour

The purpose of this research was to assess how the motor learning skills in 7-years old soccer players can be improved by preventing an internal focus of attention via the use coloured shoes. We painted the classic black soccer shoes in six areas corresponding to six regions of the foot with which it is possible to interact with the ball. Thirty-four 7-years-old soccer players were randomized to two groups (Coloured n = 17 and Black, n = 17) to perform four basic football manoeuvres/tasks: reception (RECP), passing (PASS), ball management (MAGT), and shooting (SHOT). We found highly significant differences (P<0.001) in all four performance tests: mean(sd) RECP: 0.82(0.07) vs. 0.45(0.12); PASS: 0.85(0.07) vs. 0.47(0.09); MAGT: 0.91(0.09); SHOT: 1.00(1.00) vs. 0.44(0.16). Colored shoes appear to draw children’s attention away from body centered cues without explicit verbal communications. We propose that this cognitive adaptation enhanced the technical gesture by preventing the negative processes associated with action constraining when adopting an internal focus attention (perhaps by allowing the foot to adapt to surfaces and movements more naturally than conditions that promote a focus on the body movement). Consequently, this type of coloured footwear could be used during childhood to allow children to enhance the performance of basic football exercises through preventing action constraining and promoting intuitive (non-body centered) action knowledge.

When mathematics meets physical activity in the school-aged child: The effect of an integrated motor and cognitive approach to learning geometry

Mathematics is a science which can lead to both anxiety in children and teaching difficulties in teachers. Together, these two difficulties can increase the time spent in teaching and learning mathematics. The aim of this study is to examine the efficiency of a new integrated mathematics/geometry and physical activity program, specifically structured for increasing learning in fourth-grade pupils. Thirty-six children (age 10.36±0.55) were divided into an experimental (n1 = 19) group and a control (n2 = 17) group. The experimental group of subjects learned mathematics and geometry via the integrated teaching method, while the control group of subjects learned these subjects via traditional teaching methods. We administered two ad hoc tests, before and after the intervention, in order to study its effect. One test was on geometry knowledge and the other on mathematics, in which there were questions about the implemented teaching topics: rectangles, squares and their perimeters. Using a factorial 2×2 ANOVA, the results after four weeks indicated that the group of subjects who gained their mathematics and geometry knowledge through our intervention program were significantly more successful (P<0.05) than the control group. Our results suggest that the integrated teaching method proposed here could be considered a useful and efficient method for teaching mathematics and geometry based on motor tasks.

Letter to the Editor concerning “Effects of lumbosacral orthoses on postural control in individuals with or without non-specific low back pain” by J. Mi et al. (Eur Spine J; 2017: DOI 10.1007/s00586-017-5355-5)

According to the literature low back pain is one of the most costly and common healthcare problems [1]. To date, writing ‘low back pain [tiab]’ on PubMed.gov we can find 22,695 articles. For these reasons, it is very important to take into account a solid statistical approach in order to publish an article on this topic. Several letters or technical notes on statistics approach and scientific terminologies [2] were published in scientific journals in the last years to prompt best practices about statistics in scientific writing. In our opinion, the article entitled “Effects of lumbosacral orthoses on postural control in individuals with or without non‐specific low back pain” [3] shown several flaws that may change the conclusions. The aim of this letter is to highlight essential errors and/or omissions we think this paper has. Some points will be addressed in this letter to better explain the state of the art regarding the topic described in the analyzed article.

Comments on “Camptocormia as presenting in lower motor neuron disease with TARDBP mutation: case report”

Recently, Camptocormia raised some interest as a motor neuron disease symptom as shown in a recent letter [1]. We read on the Neurological Sciences journal that piece, entitled BCamptocormia as presenting in lower motor neuron disease with TARDBP mutation: case report^. We think that this letter, reporting a case report, is worthy of stronger methodological support. Some reflections on this piece point out what is yet necessary to do to support authoritatively the effectiveness of its approach. Particularly, the methodological approach shows some severe flaws, which might undermine result interpretation. Therefore, this letter aims at suggesting the study’s improvements to achieve stronger conclusions on the treated matter. In introduction, the authors wrote: BMutations in the TARDBP gene were detected in 1%...^, but this result was not confirmed by Scotter et al. [2], despite the authors citing their article. Not to mention the fact that in some cases such a small percent value could be mistaken for a Bsignal^ while being more likely a Bnoise^ [3]. Furthermore, the authors omit to provide any data about: