The “Adipo-Cerebral” Dialogue in Childhood Obesity: Focus on Growth and Puberty. Physiopathological and Nutritional Aspects

Overweight and obesity in children and adolescents are overwhelming problems in western countries. Adipocytes, far from being only fat deposits, are capable of endocrine functions, and the endocrine activity of adipose tissue, resumable in adipokines production, seems to be a key modulator of central nervous system function, suggesting the existence of an “adipo-cerebral axis.” This connection exerts a key role in children growth and puberty development, and it is exemplified by the leptin–kisspeptin interaction. The aim of this review was to describe recent advances in the knowledge of adipose tissue endocrine functions and their relations with nutrition and growth. The peculiarities of major adipokines are briefly summarized in the first paragraph; leptin and its interaction with kisspeptin are focused on in the second paragraph; the third paragraph deals with the regulation of the GH-IGF axis, with a special focus on the model represented by growth hormone deficiency (GHD); finally, old and new nutritional aspects are described in the last paragraph.

Cortical spheroids display oscillatory network dynamics

Three-dimensional brain cultures can facilitate the study of central nervous system function and disease, and one of the most important components that they present is neuronal activity on a network level. Here we demonstrate network activity in rodent cortical spheroids while maintaining the networks intact in their 3D state. Networks developed by nine days in culture and became more complex over time. To measure network activity, we imaged neurons in rat and mouse spheroids labelled with a calcium indicator dye, and in mouse spheroids expressing GCaMP. Network activity was evident when we electrically stimulated spheroids, was abolished with glutamatergic blockade, and was altered by GABAergic blockade or partial glutamatergic blockade. We quantified correlations and distances between somas with micron-scale spatial resolution. Spheroids seeded at as few as 4,000 cells gave rise to emergent network events, including oscillations. These results are the first demonstration that self-assembled rat and mouse spheroids exhibit network activity consistent with in vivo network events. These results open the door to experiments on neuronal networks that require fewer animals and enable high throughput experiments on network-perturbing alterations in neurons and glia.

Cortical spheroids display oscillatory network dynamics

Three-dimensional brain cultures can facilitate the study of central nervous system function and disease, and one of the most important components that they present is neuronal activity on a network...

The Continuing Evolution of Insulin-like Growth Factor Signaling

The insulin-like growth factors (IGFs; IGF1/IGF2), known for their regulation of cell and organismal growth and development, are evolutionarily conserved ligands with equivalent peptides present in flies (D. melanogaster), worms (C. elegans) among others. Two receptor tyrosine kinases, the IGF1 receptor and the insulin receptor mediate the actions of these ligands with a family of IGF binding proteins serving as selective inhibitors of IGF1/2. This treatise reviews recent findings on IGF signaling in cancer biology and central nervous system function. This includes overexpression of IGF1 receptors in enhancing tumorigenesis, acquired resistance and contributions to metastasis in multiple cancer types. There is accumulating evidence that insulin resistance, a hallmark of type 2 diabetes, occurs in the central nervous system, independent of systemic insulin resistance and characterized by reduced insulin and IGF1 receptor signaling, and may contribute to dementias including Alzheimer’s Disease and cognitive impairment. Controversy over the role(s) of IGF signaling in cancer and whether its inhibition would be of benefit, still persist and extend to IGF1’s role in longevity and central nervous system function.

Opponens pollicis silent period during a precision motor task with the isometric contraction of the ipsilateral knee extension.

Objectives: To clarify the excitability of the central nervous system function via a difference in the feedback method, we examined the alterations in the duration of the silent period recorded from the opponens pollicis muscle during a precision motor task. This task involved isometric knee extension using visual feedback and verbal conduction. Design: Cross-sectional study with an A-B-A task-order design. Methods: 12 healthy adults (7 males and 5 females; mean age: 23.7 ± 2.1 years) participated in this study. SP was recorded from the opponens pollicis muscle during a precision motor task involving with isometric contraction during ipsilateral knee extension with constant torque by two kinds of feedback. The precision motor task was carried out as follows; Subjects maintained knee extension torque at a constant strength using the BIODEX SYSTEM 3 with 60° of knee flexion. The knee extension torque was set at 25% of individual maximum effort. We monitored the torque using two methods. The first method used subjects’ own visual feedback with gazing at the BIODEX screen (Task A). The second task featured torque adjustment by the examiner’s verbal instruction. Subjects’ eyes were bandaged to eliminate visual feedback (Task B). Silent period was recorded from the opponens pollicis muscle while subjects maintained ipsilateral isometric knee extension during an A-B-A task order. As a stimulus condition, a constant current rectangular wave with a frequency of 0.5 Hz and a duration of 0.2 ms, was added 16 times in the median nerve at the wrist with the intensity of supra-maximum, which maximal M wave was evoked. We compared the duration of silent period between tasks in each dominant and non-dominant side. Results: The duration of silent period on the dominant leg was 109.1 ± 5.2 ms (Task A), 105.2 ± 7.2 ms (Task B), and 107.6 ± 6.7 ms (Task A). And that on the non-dominant leg was 111.3 ± 6.1 ms (Task A), 105.9 ± 4.4 ms (Task B), and 109.3 ± 4.4 ms (Task A). There was no significant difference on the dominant leg side. However, during Task B on the non-dominant leg side, the duration of silent period was shortened (Tukey’s test, p = 0.01, 0.08). Conclusion: During less-skilled motor adjustment using the non-dominant leg, the motor control with verbal conduction and no visual feedback requires more afferent activation. In these cases, central nervous system function excitability associated with ipsilateral upper extremity increases, even if the task involves the lower extremity.

Intraoperative Monitoring of Central Neurophysiology

This chapter covers neurophysiological intraoperative monitoring (NIOM). It describes the relevant neurophysiological signals, their anatomical sources, the techniques used to record them, the manner in which they are assessed, and possible causes of intraoperative signal changes. Techniques used include electroencephalography (EEG), electromyography, and auditory, somatosensory, and motor evoked potentials. Some of these techniques can be used to localize and identify areas of cerebral cortex or the corticospinal tract. Recording of the electromyogram generated by reflex activity can be used to evaluate central nervous system function in some circumstances. EEG can be used to assess depth of anesthesia. Signals can be affected by anesthesia, and the chapter discusses various anesthetic agents, their effects on signals, and considerations for anesthetic management during NIOM. Personnel performing NIOM must be knowledgeable about the anatomy and physiology underlying the signals, the technology used to record them, and the factors (including anesthesia) that can affect them.

Inducible Knockout of Mouse Zfhx3 Emphasizes Its Key Role in Setting the Pace and Amplitude of the Adult Circadian Clock

The transcription factor zinc finger homeobox 3 (ZFHX3) plays a key role in coupling intracellular transcriptional-translational oscillations with intercellular synchrony in mouse suprachiasmatic nucleus (SCN). However, like many key players in central nervous system function, ZFHX3 serves an important role in neurulation and neuronal terminal differentiation while retaining discrete additional functions in the adult SCN. Recently, using a dominant missense mutation in mouse Zfhx3, we established that this gene can modify circadian period and sleep in adult animals. Nevertheless, we were still concerned that the neurodevelopmental consequences of ZFHX3 dysfunction in this mutant may interfere with, or confound, its critical adult-specific roles in SCN circadian function. To circumvent the developmental consequences of Zfhx3 deletion, we crossed a conditional null Zfhx3 mutant to an inducible, ubiquitously expressed Cre line (B6.Cg-Tg(UBC-cre/ERT2)1Ejb/J). This enabled us to assess circadian behavior in the same adult animals both before and after Cre-mediated excision of the critical Zfhx3 exons using tamoxifen treatment. Remarkably, we found a strong and significant alteration in circadian behavior in tamoxifen-treated homozygous animals with no phenotypic changes in heterozygous or control animals. Cre-mediated excision of Zfhx3 critical exons in adult animals resulted in shortening of the period of wheel-running in constant darkness by more than 1 h in the majority of homozygotes while, in 30% of animals, excision resulted in complete behavioral arrhythmicity. In addition, we found that homozygous animals reentrain almost immediately to 6-h phase advances in the light-dark cycle. No additional overt phenotypic changes were evident in treated homozygous animals. These findings confirm a sustained and significant role for ZFHX3 in maintaining rhythmicity in the adult mammalian circadian system.