Annals of Neurosciences最新文献

Background: It is currently accepted that sign languages and spoken languages have significant processing commonalities. The evidence supporting this often merely investigates frontotemporal pathways, perisylvian language areas, hemispheric lateralization, and event-related potentials in typical settings. However, recent evidence has explored beyond this and uncovered numerous modality-dependent processing differences between sign languages and spoken languages by accounting for confounds that previously invalidated processing comparisons and by delving into the specific conditions in which they arise. However, these processing differences are often shallowly dismissed as unspecific to language.

Summary: This review examined recent neuroscientific evidence for processing differences between sign and spoken language modalities and the arguments against these differences' importance. Key distinctions exist in the topography of the left anterior negativity (LAN) and with modulations of event-related potential (ERP) components like the N400. There is also differential activation of typical spoken language processing areas, such as the conditional role of the temporal areas in sign language (SL) processing. Importantly, sign language processing uniquely recruits parietal areas for processing phonology and syntax and requires the mapping of spatial information to internal representations. Additionally, modality-specific feedback mechanisms distinctively involve proprioceptive post-output monitoring in sign languages, contrary to spoken languages' auditory and visual feedback mechanisms. The only study to find ERP differences post-production revealed earlier lexical access in sign than spoken languages. Themes of temporality, the validity of an analogous anatomical mechanisms viewpoint, and the comprehensiveness of current language models were also discussed to suggest improvements for future research.

Key message: Current neuroscience evidence suggests various ways in which processing differs between sign and spoken language modalities that extend beyond simple differences between languages. Consideration and further exploration of these differences will be integral in developing a more comprehensive view of language in the brain.

Background: Sympathetic innervation of lymphoid organs, and the presence of 17β-estradiol (estrogen or E2) and adrenergic receptors (ARs) on lymphocytes, suggests that sympathetic stimulation and hormonal activation may influence immune functions.

Purpose: Modeling and simulating these pathways may help to understand the dynamics of neuroendocrine-immune modulation at the cellular and molecular levels.

Methods: Dose- and receptor-dependent effects of E2 and AR subtype-specific agonists were established in vitro on lymphocytes from young male Sprague-Dawley rats and were modeled in silico using the MATLAB Simbiology toolbox. Kinetic principles were assigned to define receptor-ligand dynamics, and concentration/time plots were obtained using Ode15s solvers at different time intervals for key regulatory molecules. Comparisons were drawn between in silico and in vitro data for validating the constructed model with sensitivity analysis of key regulatory molecules to assess their individual impacts on the dynamics of the system. Finally, docking studies were conducted with key ligands E2 and norepinephrine (NE) to understand the mechanistic principles underlying their interactions.

Results: Adrenergic activation triggered proapoptotic signals, while E2 enhanced survival signals, showing opposing effects as observed in vitro. Treatment of lymphocytes with E2 shows a 10-fold increase in survival signals in a dose-dependent manner. Cyclic adenosine monophosphate (cAMP) activation is crucial for the activation of survival signals through extracellular signal-regulated kinase (p-ERK) and cAMP responsive element binding (p-CREB) protein. Docking studies showed the direct inhibition of ERK by NE and β2-AR by E2 explaining how estrogen signaling overrides NE-mediated immunosuppression in vitro.

Conclusion: The cross-talk between E2 and adrenergic signaling pathways determines lymphocyte functions in a receptor subtype and coactivation-dependent manner in health and disease.

Background: Human neurodegenerative diseases occur as a result of various factors. Regardless of the variety in the etiology of development, many of these diseases are characterized by the accumulation of pathological, misfolded proteins; hence, such diseases are considered as proteinopathies. While plenty of research study has been conducted in order to identify the pathophysiology of these proteinopathies, there is still a lack of understanding in terms of potential therapeutic targets.

Summary: Molecular chaperones present the main workforce for cellular protection and stress response. Therefore, considering these functions, molecular chaperones present a promising target for research within the field of conformational diseases that arise from proteinopathies. Since the association between neurodegenerative disorders and their long-term consequences is well documented, the need for the development of new therapeutic strategies becomes even more critical.

Key message: In this review, we summarized the molecular function of heat shock proteins and recent progress on their role, involvement, and other mechanisms related to neurodegeneration caused by different etiological factors. Based on the relevant scientific data, we will highlight the functional classification of heat shock proteins, regulation, and their therapeutic potential for neurodegenerative disorders.

Background: Absence seizures (petit mal seizures) are characterized by a brief loss of consciousness without loss of postural tone. The disease is diagnosed by an electroencephalogram (EEG) showing spike-wave discharges (SWD) caused by hypersynchronous thalamocortical (TC) oscillations. There has been an explosion of research highlighting the role of astrocytes in supporting and modulating neuronal activity. Despite established in vitro evidence, astrocytes' influence on the TC network remains to be elucidated in vivo in the absence epilepsy (AE).

Purpose: In this study, we investigated the role of astrocytes in the generation and modulation of SWDs. We hypothesize that disturbances in astrocytes' function may affect the pathomechanism of AE.

Methods: To direct the expression of channelrhodopsin-2 (ChR2) rAAV8-GFAP-ChR2(H134R)-EYFP or to control the effect of surgical intervention, AAV-CaMKIIa-EYFP was injected into the ventrobasal nucleus (VB) of the thalamus of 18 animals. After four weeks following the injection, rats were stimulated using blue light (~473 nm) and, simultaneously, the electrophysiological activity of the frontal cortical neurons was recorded for three consecutive days. The animals were then perfused, and the brain tissue was analyzed by confocal microscopy.

Results: A significant increase in the duration of SWD without affecting the number of SWD in genetic absence epileptic rats from Strasbourg (GAERS) compared to control injections was observed. The duration of the SWD was increased from 12.50 ± 4.41 s to 17.44 ± 6.07 following optogenetic stimulation in GAERS. The excitation of the astrocytes in Wistar Albino Glaxo Rijswijk (WAG-Rij) did not change the duration of SWD; however, stimulation resulted in a significant increase in the number of SWD from 18.52 ± 11.46 bursts/30 min to 30.17 ± 18.43 bursts/30 min. Whereas in control injection, the duration and the number of SWDs were similar at pre- and poststimulus. Both the background and poststimulus average firing rates of the SWD in WAG-Rij were significantly higher than the firing recorded in GAERS.

Conclusion: These findings suggest that VB astrocytes play a role in modulating the SWD generation in both rat models with distinct mechanisms and can present an essential target for the possible therapeutic approach for AE.