Acta neurobiologiae experimentalis最新文献

Interhemispheric communication is a fundamental feature of the mammalian brain, supporting the bilateral integration of sensory, motor, cognitive, and emotional processes. While the corpus callosum has long been recognized as the principal commissural pathway, recent advances have illuminated a far more complex molecular and circuit‑level architecture. This review synthesizes evidence from neuroanatomy, electrophysiology, molecular neuroscience, and neuroimaging to outline how interhemispheric signaling is organized and dynamically regulated. Fast excitatory and inhibitory neurotransmission provides the scaffold for callosal transfer, while neuromodulatory systems, including dopaminergic, cholinergic, serotonergic, and noradrenergic pathways, introduce a chemical layer of regulation that tunes excitability, synchrony, and hemispheric dominance. Developmental processes involving axon guidance molecules and neurotrophins shape the establishment of commissural networks, whereas activity‑dependent plasticity refines functional architecture of these networks across the lifespan. Importantly, interhemispheric interactions are not static but fluctuate dynamically according to behavioral demands, as demonstrated by recent models of dynamic laterality. Disruption of these lateralized processes is implicated in a broad spectrum of conditions, including stroke, dyslexia, autism spectrum disorder, schizophrenia, and mood disorders. By bridging cellular, molecular, and systems‑level insights, this review highlights interhemispheric communication as a key organizing principle of brain function and a promising target for therapeutic interventions aimed at restoring interhemispheric balance.

Astrocytes express a set of neurotransmitter receptors (glioreceptors) that enable them to regulate synaptic transmission and neuroplasticity, and to function as integral partners in synaptic signaling and the modification of neural circuits. This review presents the current understanding of how glioreceptors on astrocytes (astro‑gliorecptors) mediate bidirectional communication between neurons and glia across major neurotransmitter systems. The review focuses on receptors for glutamate, GABA, acetylcholine, monoamines, neuropeptides, opioids, and purines. Through these receptors, astrocytes can modulate synaptic strength, LTP and LTD expression, network dynamics, and state‑dependent modulation of arousal and reward circuits. Despite potentially having lower receptor density than neurons, astrocytes can amplify their functional impact through unique structural properties, such as extensive process arborisation, contact with thousands of synapses, and the formation of electrically coupled syncytia that propagate calcium waves across neural networks. Metabolic integration via glycogen regulation, lactate production, and gliotransmitter release modulates neuronal excitability and synaptic strength. Therefore, astrocytes can be viewed as integrators of neuronal activity patterns and gatekeepers of experience‑dependent plasticity, essential for maintaining synaptic homeostasis and enabling adaptive behavioral responses. Astro‑glioreceptors dysfunctions contribute to neurological and psychiatric disorders, including Alzheimer's disease, Parkinson's disease, epilepsy, and depression. Therefore, targeting specific glioreceptor subtypes represents a promising therapeutic strategy for modulating neural circuits while minimizing neuronal side effects.

Peripheral nerve injuries occur due to accidents and in manufacturing every day. Unlike the central nervous system, injured peripheral nerves can self‑regenerate after injury. The study explored changes in gene expression and related biological processes after peripheral nerve injury and regeneration. Male Sprague‑Dawley rats were divided into six groups and underwent sciatic nerve resection followed by recovery for 0, 3, 6, 10, 15, and 20 days; distal sciatic nerve segments were collected for sequencing, real‑time quantitative polymerase chain reaction (RT‑qPCR), and Western blotting. According to DNA microarray analysis, approximately 5,000 genes were differentially expressed, and six biological processes were identified at different time points after nerve transection, with expression mainly observed in the mid and latter stages after injury. Four genes (UDP glycosyltransferase 8 [Ugt8], C‑C motif chemokine ligand 2 [Ccl2], neuregulin 1 [Nrg1], and heme oxygenase‑1 [Hmox1]) with nerve regeneration‑specific function were selected for further verification using RT‑qPCR and Western blot. The results demonstrated that genes such as Ugt8 decreased initially and then peaked at 20 days, whereas Ccl2 and Hmox1 both exhibited two peaks at three and 20 days. Nrg1 showed a gradual increase, peaking around 15 days. The study identified differential gene expression in distal nerve segments during Wallerian degeneration and analyzed the associated dynamic biological changes. The findings provide insights into research on peripheral nerve injury and regeneration, and further studies will involve screening key genes and more detailed investigations.

Myosin VI (MVI) is a unique unconventional myosin which, unlike other myosins, moves towards the minus end of actin filaments. It is involved in numerous cellular processes such as endocytosis and trafficking, cell migration and adhesion, and gene transcription. It is widely expressed in all tissues, including the brain. Its lack in adult murine brains is associated with gliosis and impairment of neuronal transmission. Here, we demonstrate that the MVI level in the total mouse brain and its regions (cerebral cortex, cerebellum, and hippocampus) increases with the animal's age (from newborn up to 12‑month‑old mice). Its lack leads to enlargement of the brain and its examined areas, and an increase of the level of GFAP, the marker of glia cells, in adult mice. The data indicate an involvement of MVI in the brain maturation and possibly in development of an age‑dependent gliosis.

The role of prefrontal somatostatin interneurons in emotion recognition is well characterized. Here, for the first time, we investigated the role of these neurons during remote transfer of emotional information in the safe environment of the home cage. To do that mice with fluorescently labelled somatostatin interneurons were housed in pairs for three weeks, one labelled an Observer, and the other a Demonstrator. In the test session, the Demonstrator was subjected to aversive stimuli outside of the home cage, while the Observer remained there undisturbed. Upon the return of the Demonstrator to the home cage, we recorded the interactions of the two animals. The behavior of both partners, assessed and classified with machine learning algorithms, was clearly affected by the emotional state of the Demonstrator. To assess the role of prefrontal somatostatin interneurons in this process we chemogenetically manipulated their activity in the Observers and found that activation of these cells abolishes the enhanced social investigation of a stressed Demonstrator. This is associated with disinhibition of the prefrontal cortex. The manipulation also affects the neuronal activation patterns in Demonstrators, which seems to reflect the change in the behavior of the Observers.

Angiotensin‑(1‑7) [Ang‑(1‑7)] exerts physiological effects in the brain mediated by its receptor, Mas. Recent studies have successfully demonstrated that Ang‑(1‑7) exerts neuroprotective effects following cerebral ischemia in a rat model. However, prior investigations utilized direct intracerebral cannulation for Ang‑(1‑7) delivery, potentially limiting human application. Hematopoietic stem cells (HSC) have been previously demonstrated to mobilize to the site of cerebral injury in response to stroke. Therefore, we sought to examine the therapeutic potential of HSC transduced via a lentivirus with Ang‑(1‑7) to migrate to the ischemic hemisphere and overexpress Ang‑(1‑7) following stroke. Animals were divided into 3 groups: Stroke + PBS, Stroke + HSC, Stroke + Ang‑(1‑7)‑transduced HSC. Bone marrow from separate animals was harvested and used for injection of the HSC, with or without lentivirus induced Ang‑(1‑7) transduction. A neurological assessment was performed at 72 hours post‑surgery. Ang‑(1‑7) transduced HSC secreted the peptide up to 72 hours post infection, in vitro. Stroked animals injected with the Ang‑(1‑7) infected HSC exhibited reduced behavioral deficits on the Bederson neurological assessment scale. These data suggest that HSC‑mediated delivery of Ang‑(1‑7) to ischemic brain appears to improve post‑stroke outcomes and may offer a novel route of therapeutic agent delivery to the brain.

Diabetes is the most common cause of vision deterioration and subsequent vision loss in people worldwide. Long-term hyperglycemia causes structural, neurovascular and metabolic changes in the eye, leading to a progressive loss of light sensitive retinal cells, degeneration of retinal layers and neuroinflammation of optic nerve fibers and, if not treated, leading to the development of diabetic retinopathy and optic nerve damage. Growing evidence indicates that the pathological changes observed in the retina and optic nerve affected by prolonged hyperglycemia might results from several interconnected molecular events and biochemical signaling cascades such as excessive protein glycation, increased oxidative stress and local inflammation triggered by the receptor for advanced glycation end‑products (RAGE) along with the upregulation of molecules involved in angiogenesis and cytoskeleton modification including vascular endothelial growth factor (VEGF) and RhoA/Diaph1/profilin1 system. In this review, we focus on the latest advances in uncovering major factors involved in the pathogenesis of diabetic retinopathy and discuss novel, non‑invasive treatment options aimed at the cause rather than symptoms of the disease.

The present study aims to elucidate the role of the Sigma‑1 receptor in the pathogenesis of neuropathic pain and evaluate its potential therapeutic implications. To systematically assess the effects of the Sigma‑1 receptor, neuropathic pain was induced in rats using the chronic constriction injury (CCI) model. Subjects were subsequently divided into three groups: Sham, CCI, and CCI+BD1047 (where BD1047 is a Sigma‑1 receptor antagonist). Following intrathecal administration of the respective agents, thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) were measured. Additionally, Western blotting was utilized to examine Sigma‑1 receptor, phosphorylated protein kinase Cα (p‑PKCα), and P2X3 receptor expression in the dorsal root ganglia (DRG). Immunofluorescence techniques were employed to examine p‑PKCα and P2X3 receptor expression. The results indicate a direct correlation between Sigma‑1 receptor activity and pain perception, evidenced by changes in TWL and MWT. In the CCI group, both TWL and MWT were significantly reduced compared to the Sham group. Furthermore, protein levels of the Sigma‑1 receptor, p‑PKCα, and P2X3 receptor in the DRG were elevated, and immunofluorescence expression of p‑PKCα and the P2X3 receptor also increased. Conversely, in the CCI+BD1047 group, TWL and MWT were significantly enhanced. Additionally, protein levels of the Sigma‑1 receptor, p‑PKCα, and P2X3 receptor in the DRG decreased, along with reduced immunofluorescence expression of p‑PKCα and P2X3 receptor. The findings indicate that neuropathic pain is intricately associated with the Sigma‑1 receptor, p‑PKCα, and P2X3 receptor in the dorsal root ganglia. Notably, the Sigma‑1 receptor regulates the expression of p‑PKCα and P2X3 receptor, presenting a novel therapeutic target for neuropathic pain management.

The aim of the study was to investigate if body balance control deficits in dyslexia are present in dyslexic adults and if unstable binocular fixation relates to impaired body balance. Fifteen dyslexics adults and 15 age‑matched non‑dyslexics participated in the study. Posturography data were collected in two sessions: during quiet standing (single‑task) and while performing a mental task while standing on the platform (dual‑task). Each session was conducted under three distinct visual conditions: monocular fixation, binocular fixation, and eyes closed. Four parameters of the center of pressure (CoP) signal were analysed: medio‑lateral sway (XSD), antero‑posterior sway (YSD), sway area (Area95) and mean CoP velocity (Vavg). A psycho‑physical tests with Wesson card and a modified Mallett test were used to measure fixation disparity (FD). Slight underconvergence at the fixation point results in exo‑FD, and conversely, overconvergence results in eso‑FD. The results indicated that in dyslexics, the exo‑FD values were higher than in controls. In both groups, body stabilization was better with binocular fixation compared to eyes closed (lowest value of Vavg and CoP sway). Moreover, dyslexic adults demonstrated impaired body balance. The posturographic deficits remained unaltered by the viewing conditions, indicating that binocular fixation did not contribute to body instability, despite the higher incidence of fixation disparity in the dyslexic group. The existence of both posturographic deficits and the presence of FD may reflect deficits at the cerebellar level.

Opioid dependence is strongly associated with moderate to severe depression and anxiety. The primary objective of this investigation was to determine whether coenzyme Q10 (CoQ10) has the capacity to increase the level of glial cell line‑derived neurotrophic factor (GDNF), with the aim of ameliorating anxiety‑ and depression‑like behaviors in morphine (MOP)‑dependent rats. In this study, 40 male Wistar rats were randomly divided into five experimental groups: Oil group, MOP+Oil group, MOP+Q10‑100 group, MOP+Q10‑200 group, and MOP+Q10‑400 group. Rats received escalating doses of MOP (25 to 100 mg/kg, s.c.) once daily. After 21 days of drug dependency, CoQ10 was administered orally at doses of 100, 200, and 400 mg/kg once daily for four weeks. Behavioral assessments were conducted using the open field test, elevated plus maze, and forced swim test. GDNF expression in the hippocampus was evaluated using immunohistochemistry. Four weeks of CoQ10 treatment significantly improved anxiety‑ and depression‑like behaviors induced by MOP administration. Furthermore, CoQ10 significantly increased GDNF expression in the hippocampus. Oral administration of CoQ10 at doses of 100, 200, and 400 mg/kg over four weeks significantly reduced depressive‑ and anxiety‑related behaviors associated with prolonged MOP exposure. These behavioral improvements were accompanied by increased hippocampal GDNF expression.