Frontiers in Neuroanatomy最新文献

Pío Del Río Hortega (1882-1945) was a giant of modern neuroscience and perhaps the most impactful member of Cajal's School. His contributions to clarifying the structure of the nervous system were key to understanding the brain beyond neurons. He uncovered microglia and oligodendrocytes, the latter until then named mesoglia. Most importantly, the characterization of oligodendroglia subtypes he made has stood the omics revolution that added molecular details relevant to comprehend their biological properties. Astounding as it may seem on today's eyes, he postulated a century ago that oligodendrocytes provide trophic support to axons, an idea that is now beyond doubt and under scrutiny as dysfunction at the axon-myelin unit is key to neurodegeneration. Here, we revised recent key advancements in oligodendrocyte biology that shed light on Hortega's ideas a century ago.

The enteric nervous system (ENS) has garnered increasing scientific interest due to its pivotal role in digestive processes and its involvement in various gastrointestinal and central nervous system (CNS) disorders, including Crohn's disease, Parkinson's disease, and autism. Despite its significance, the ENS remains relatively underexplored by neurobiologists, primarily because its structure and function are less understood compared to the CNS. This review examines both pioneering methodologies that initially revealed the intricate layered structure of the ENS and recent advancements in studying its three-dimensional (3-D) organization, both in fixed samples and at a functional level, ex-vivo or in-vivo. Traditionally, imaging the ENS relied on histological techniques involving sequential tissue sectioning, staining, and microscopic imaging of single sections. However, this method has limitations representing the full complexity of the ENS's 3-D meshwork, which led to the development of more intact preparations, such as whole-mount preparation, as well as the use of volume imaging techniques. Advancements in 3-D imaging, particularly methods like spinning-disk confocal, 2-photon, and light-sheet microscopies, combined with tissue-clearing techniques, have revolutionized our understanding of the ENS's fine structure. These approaches offer detailed views of its cellular architecture, including interactions among various cell types, blood vessels, and lymphatic vessels. They have also enhanced our comprehension of ENS-related pathologies, such as inflammatory bowel disease, Hirschsprung's disease (HSCR), and the ENS's involvement in neurodegenerative disorders like Parkinson's (PD) and Alzheimer's diseases (AD). More recently, 2-photon or confocal in-vivo imaging, combined with transgenic approaches for calcium imaging, or confocal laser endomicroscopy, have opened new avenues for functional studies of the ENS. These methods enable real-time observation of enteric neuronal and glial activity and their interactions. While routinely used in CNS studies, their application to understanding local circuits and signals in the ENS is relatively recent and presents unique challenges, such as accommodating peristaltic movements. Advancements in 3-D in-vivo functional imaging are expected to significantly deepen our understanding of the ENS and its roles in gastrointestinal and neurological diseases, potentially leading to improved diagnostic and therapeutic strategies.

Introduction: A growing body of evidence suggests that the gut microbiome may contribute to changes in brain morphology. The microbiota-gut-brain axis (MGBA) has been shown to influence neurogenesis, axon myelination, and synapse structure. However, it remains unclear whether the MGBA can influence the morphology and density of inhibitory GABAergic interneurons. The aim of this study was to determine whether antibiotic-induced dysbiosis (AID) is associated with alterations in dendritic morphology of GABAergic inhibitory interneurons in the medial entorhinal cortex (mEC), somatosensory cortex (SSC), motor cortex (MC), and hippocampus (Hp).

Methods: A cohort of six-month-old GAD-67-EGFP transgenic mice was treated with an antibiotic cocktail for two weeks, resulting in gut dysbiosis as validated by collecting stool samples at baseline and after treatment, then using next-generation sequencing of 16S ribosomal RNA.

Results: The results demonstrate that the proposed model effectively exhibited the defining features of gut dysbiosis, including a significant reduction in microbiome diversity, expansion of pathobionts, and loss of beneficial microbes. The AID group showed alterations in density and morphology of GABAergic interneurons in different brain areas. The mean dendritic length and mean dendritic segments of the SSC and Hp were found to be significantly decreased, while no such decrease was observed in the mEC or MC. Furthermore, the density of interneurons was decreased in the mEC, Hp, and SSC areas, while no change was observed in the MC area.

Discussion: The interneuron dysfunction plays a role in the pathogenesis of neurological disease. The findings of this study suggest that AID potentially influences the density and morphology of the interneurons, which may contribute to the development of neurological disorders.

Healthy brain development hinges on proper myelination, with disruption contributing to a wide array of neurological disorders. Immunohistochemical analysis of myelin basic protein (MBP) is a fundamental technique for investigating myelination and related disorders. However, despite decades of MBP research, detailed accounts of normal MBP progression in the developing mouse brain have been lacking. This study aims to address this gap by providing a detailed spatiotemporal account of MBP distribution across 13 developmental ages from postnatal day 2 to 60. We used an optimized immunohistochemistry protocol to overcome the challenges of myelin's unique lipid-rich composition, enabling more consistent staining across diverse brain structures and developmental stages, offering a robust baseline for typical myelination patterns, and enabling comparisons with pathological models. To support and potentially accelerate research into myelination disorders, we have made >1,400 high-resolution micrographs accessible online under the Creative Commons license.

Introduction: The striatum (St) integrates cognitive, motor, and limbic functions and plays a critical role in processing emotions, motivation, and rewards. It may undergo several morphophysiological changes in neuropsychiatric diseases. Depression, a complex psychiatric disorder, affects millions of people around the world and leads to an increased risk of suicide, decreased quality of life, and functional impairment. Conventional treatments require prolonged use, leading to drug resistance; thus, new treatments and therapeutic strategies have been widely studied. Ayahuasca results from the joint infusion of the Banisteriopsis caapi vine and Psychotria viridis leaves have psychoactive properties, and its use in depression has shown promising results. Our objective was to morphoquantitatively evaluate the effects of ayahuasca on the St in an already validated model of juvenile depression induced in a non-human primate.

Methods: Six marmosets were divided into three groups of two animals each. One group was kept in family life (FG), and two groups were socially isolated (IG). Isolation was carried out by separating the animal from all others in the colony. One of the isolated groups received doses of ayahuasca tea (AG) 3 days before and two times during the isolation period, while the other groups received the same dose of placebo. After 13 weeks of experimentation, euthanasia, and transcardiac perfusion were performed. The brains were sectioned and stained with thionin using the Nissl method. We employed stereological techniques to assess the striatum and investigate potential alterations in neuronal volume in socially isolated animals treated with ayahuasca. Equidistant sections of the caudate and putamen were analyzed for all measurements and selected by systematic and uniform sampling.

Results and discussion: Striatal neurons in the IG group exhibited significantly smaller volumes compared to those in the FG and AG groups. Our findings suggest that ayahuasca may prevent extensive neuronal volume loss, as observed in the IG, by acting as a prophylactic agent and buffering neural structural changes during chronical social isolation.

The microbiota-gut-brain axis (MGBA) plays a significant role in the maintenance of brain structure and function. The MGBA serves as a conduit between the CNS and the ENS, facilitating communication between the emotional and cognitive centers of the brain via diverse pathways. In the initial stages of this review, we will examine the way how MGBA affects neurogenesis, neuronal dendritic morphology, axonal myelination, microglia structure, brain blood barrier (BBB) structure and permeability, and synaptic structure. Furthermore, we will review the potential mechanistic pathways of neuroplasticity through MGBA influence. The short-chain fatty acids (SCFAs) play a pivotal role in the MGBA, where they can modify the BBB. We will therefore discuss how SCFAs can influence microglia, neuronal, and astrocyte function, as well as their role in brain disorders such as Alzheimer's disease (AD), and Parkinson's disease (PD). Subsequently, we will examine the technical strategies employed to study MGBA interactions, including using germ-free (GF) animals, probiotics, fecal microbiota transplantation (FMT), and antibiotics-induced dysbiosis. Finally, we will examine how particular bacterial strains can affect brain structure and function. By gaining a deeper understanding of the MGBA, it may be possible to facilitate research into microbial-based pharmacological interventions and therapeutic strategies for neurological diseases.

Previous studies on changes in the distribution of GABAergic interneurons and excitation/inhibition (E/I) balance in Alzheimer's disease (AD) and aging were mainly conducted in the neocortex and hippocampus. However, the limbic system is the primary and crucial location for AD progression. Therefore, in this study, we utilized AD and aging mouse models to investigate the E/I balance and the distribution of parvalbumin (PV)- and somatostatin (SST)-expressing cells in S1BF (barrel field of primary somatosensory cortex, barrel cortex), CA1 hippocampal area and brain regions beyond the neocortex and hippocampus, including retrosplenial cortex (RSC, which is composed of RSG and RSA), piriform cortex (Pir), amygdala (BMA), and hypothalamus (DM). We discovered that amyloidosis may disrupt the alignment of excitatory pre- and postsynaptic quantities. Amyloidosis reduces the quantity of synapses and SST cells, but does not impact the counts of PV cells. By contrast, aging is linked to a decline in synapses, I/E ratios, SST and PV cells. Amyloidosis affects the S1BF and BMA, while aging may harm all studied regions, including the S1BF, RSC, hippocampus, Pir, BMA, and DM. Aging mostly affects synapses and I/E ratios in Pir, BMA, and DM, and PV and SST interneurons in the hippocampus.

Introduction: Most of what is known about thalamic development comes from rodent studies, however, the increased proportion of human association cortex has co-evolved with increased thalamocortical connectivity. Higher order thalamic nuclei, relaying information between cortical regions and important in higher cognitive function, are greatly expanded.

Methods: This study mapped the emergence of thalamic nuclei in human fetal development (8-16 post conceptional weeks; PCW) by revealing gene expression patterns using in situ hybridization and immunohistochemistry for previously established thalamic development markers.

Results: In the proliferative thalamic ventricular zone, OLIG3 and NR2F1 immunoreactivity marked the extent of the thalamus, whereas PAX6 and NR2F2 were expressed in gradients, suggesting an early protomap. This was also the case for post-mitotic transcription factors ZIC4, GBX2, FOXP2 and OTX2 which marked thalamic boundaries but also exhibited opposing gradients with ZIC4 expression higher anterior/lateral, and GBX2, FOXP2 and OTX2 higher in posterior/medial. Expression patterns became increasingly compartmentalized as development progressed and by 14 PCW recognizable thalamic nuclei were observed with, for instance, the centromedian nucleus being characterized by high FOXP2 and absent GBX2 expression. SP8-like immunoreactivity was expressed in distinct thalamic locations other than the reticular formation which has not been previously reported. Markers for GABAergic neurons and their precursors revealed the location of the prethalamus and its development into the reticular formation and zona incerta. No GAD67+ neurons were observed in the thalamus at 10 PCW, but by 14 PCW the medial posterior quadrant of the thalamus at various levels was infiltrated by GAD67+/ SOX14+ cells of presumed pretectal/midbrain origin. We compared expression of the neurodevelopmental disease susceptibility gene CNTNAP2 to these patterns. It was highly expressed by glutamatergic neurons in many thalamic regions by 14 PCW, sometimes but not always in conjunction with its upstream expression regulator FOXP2.

Conclusion: In human discrete thalamic nuclei exhibiting discrete gene expression patterns emerge relatively early from a protomap of gene expression. The migration of GABAergic neurons into the thalamus occurs over a protracted period, first from the midbrain. Disruption of CNTNAP2 activity and function could be hypothezised to have a variety of effects upon thalamic development.

Individuals misusing opioids often report heightened feelings of loneliness and decreased ability to maintain social connections. This disruption in social functioning further promotes addiction, creating a cycle in which increasing isolation drives drug use. Social factors also appear to impact susceptibility and progression of opioid dependence. In particular, increasing evidence suggests that poor early social bond formation and social environments may increase the risk of opioid abuse later in life. The brain opioid theory of social attachment suggests that endogenous opioids are key to forming and sustaining social bonds. Growing literature describes the opioid system as a powerful modulator of social separation distress and attachment formation in rodents and primates. In this framework, disruptions in opioidergic signaling due to opioid abuse may mediate social reward processing and behavior. While changes in endogenous opioid peptides and receptors have been reported in these early-life adversity models, the underlying mechanisms remain poorly understood. This review addresses the apparent bidirectional causal relationship between social deprivation and opioid addiction susceptibility, investigating the role of opioid transmission in attachment bond formation and prosocial behavior. We propose that early social deprivation disrupts the neurobiological substrates associated with opioid transmission, leading to deficits in social attachment and reinforcing addictive behaviors. By examining the literature, we discuss potential overlapping neural pathways between social isolation and opioid addiction, focusing on major reward-aversion substrates known to respond to opioids.

Background and aim: Endoscopic Third Ventriculostomy (ETV) is used to treat hydrocephalus, an abnormal cerebrospinal fluid accumulation in brain ventricles. By defining a new trajectory and entry point interval, we aim to establish a standardized approach for FreeHand ETV, a vital technique when specialized tools are unavailable, or during emergencies.

Methods: 187 MRIs were analyzed, with 30 having hydrocephalus. A pathway crossing the cranial bone, interventricular foramen (of Monro) and tuber cinereum was outlined. Measurements involved distances to cranial sutures, pathway angles and depths, and distances to important anatomical landmarks. Comparisons between hydrocephalic and non-hydrocephalic patients were made while assessing variations linked to age, sex and Evan's index.

Results: Significant differences were found, notably for depth (93.520 ± 7.228 mm), coronal plane angulation (10.982° ± 6.119°), distance to the sagittal suture (18.957 ± 8.608 mm), and distance to the superior frontal sulcus (7.00 mm). Other variables did not differ significantly between groups, including for the sagittal plane angulation (2.549° ± 3.576°) and the distances to the precentral sulcus (19.93 ± 7.955 mm), and to the coronal suture (10.55 mm).

Conclusion: The new approach, situated close to cranial sutures and distant to the precentral and superior frontal sulcus, shows promise in enhancing surgical precision and outcomes for hydrocephalus management.