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Frontiers In Neuroanatomy[JOURNAL]

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Exploring the microbiota-gut-brain axis: impact on brain structure and function.

Yassin LK, Nakhal MM, Alderei A … +4 more , Almehairbi A, Mydeen AB, Akour A, Hamad MIK

Front Neuroanat · 2025 · PMID 40012737 · Full text

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... 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.

Development of the early fetal human thalamus: from a protomap to emergent thalamic nuclei.

Alhesain M, Alzu'bi A, Sankar N … +5 more , Smith C, Kerwin J, Laws R, Lindsay S, Clowry GJ

Front Neuroanat · 2025 · PMID 39990522 · Full text

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 o... 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 , GBX2, FOXP2 and OTX2 which marked thalamic boundaries but also exhibited opposing gradients with 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+/ + cells of presumed pretectal/midbrain origin. We compared expression of the neurodevelopmental disease susceptibility gene 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.

Opioidergic tuning of social attachment: reciprocal relationship between social deprivation and opioid abuse.

Galiza Soares JA, Sutley-Koury SN, Pomrenze MB … +1 more , Tucciarone JM

Front Neuroanat · 2024 · PMID 39917739 · Full text

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 whic... 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.

Optimal trajectory of the neuroendoscope for third ventricle pavement access.

Sousa J, Silva SM, Alves H … +4 more , Carvalho B, Sousa JM, Ferreira-Pinto MJ, Andrade JP

Front Neuroanat · 2025 · PMID 39911564 · Full text

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 t... 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.

Time-lapse imaging of identified granule cells in the mouse dentate gyrus after entorhinal lesion reveals heterogeneous cellular responses to denervation.

Greco D, Drakew A, Rößler N … +3 more , Jungenitz T, Jedlicka P, Deller T

Front Neuroanat · 2024 · PMID 39906761 · Full text

Denervation of neurons is a network consequence of brain injury. The effects of denervation on neurons can be readily studied using organotypic slice cultures of entorhinal cortex and hippocampus. Following transection... Denervation of neurons is a network consequence of brain injury. The effects of denervation on neurons can be readily studied using organotypic slice cultures of entorhinal cortex and hippocampus. Following transection of the entorhino-dentate projection, granule cells (GCs) are denervated and show on average a transient loss of spines on their denervated distal dendrites but not on their non-denervated proximal dendrites. In the present study, we addressed the question how single GCs and their denervated and non-denervated segments react to entorhinal denervation. Local adeno-associated virus (AAV)-injections were employed to transduce dentate GCs with tdTomato and entorhinal projection neurons with EGFP. This made it possible to visualize both innervating entorhinal fibers and their target neurons and to identify dendritic segments located in the "entorhinal" and the "hippocampal" zone of the dentate gyrus. Confocal time-lapse imaging was used to image distal and proximal segments of single GCs after entorhinal denervation. Time-matched non-denervated cultures served as controls. In line with previous reports, average dendritic spine loss was ~30% (2-4 days post-lesion) in the denervated zone. However, individual GCs showed considerable variability in their response to denervation in both layers, and both decreases as well as increases in spine density were observed at the single cell level. Based on the standard deviations and the effect sizes observed in this study, a computer simulation yielded recommendations for the minimum number of neurons that should be analyzed in future studies using the entorhinal denervation model.

Molecular characterization of chicken DA systems reveals that the avian personality gene, , is expressed in the mitral cells of the olfactory bulb.

Fujita T, Aoki N, Mori C … +2 more , Homma KJ, Yamaguchi S

Front Neuroanat · 2025 · PMID 39886560 · Full text

Animal personalities are stable, context-dependent behavioral differences. Associations between the personality of birds and polymorphisms in the dopamine receptor D4 (DRD4) gene have been repeatedly observed. In mammals... Animal personalities are stable, context-dependent behavioral differences. Associations between the personality of birds and polymorphisms in the dopamine receptor D4 (DRD4) gene have been repeatedly observed. In mammals, our understanding of the role of the dopamine (DA) system in higher cognitive functions and psychiatric disorders is improving, and we are beginning to understand the relationship between the neural circuits modulating the DA system and personality traits. However, to understand the phylogenetic continuity of the neural basis of personality, it is necessary to clarify the neural circuits that process personality in other animals and compare them with those in mammals. In birds, the DA system is anatomically and molecularly similar to that in mammals; however, the function of DRD4 remains largely unknown. In this study, we used chicks as model birds to reveal the expression regions of the DA neuron-related markers β, and , as well as other throughout the forebrain. We found that was selectively expressed in the mitral cells of the olfactory bulb (OB). Furthermore, a detailed comparison of the expression regions of DA neurons and in the OB revealed a cellular composition similar to that of mammals. Our findings suggest that the animal personality gene is important for olfactory information processing in birds, providing a new basis for comparing candidate neural circuits for personality traits between birds and mammals.

Hodological patterning as an organizing principle in vertebrate motor circuitry.

Glover JC

Front Neuroanat · 2024 · PMID 39844798 · Full text

Hodological patterning refers to developmental mechanisms that link the location of neurons in the brain or spinal cord to specific axonal trajectories that direct connectivity to synaptic targets either within the centr... Hodological patterning refers to developmental mechanisms that link the location of neurons in the brain or spinal cord to specific axonal trajectories that direct connectivity to synaptic targets either within the central nervous system or in the periphery. In vertebrate motor circuits, hodological patterning has been demonstrated at different levels, from the final motor output of somatic and preganglionic autonomic neurons targeting peripheral motoneurons and ganglion cells, to premotor inputs from spinal and brainstem neuron populations targeting the somatic motoneurons and preganglionic autonomic neurons, to cortical neurons that delegate movement commands to the brainstem and spinal neurons. In many cases molecular profiling reveals potential underlying mechanisms whereby selective gene expression creates the link between location and axon trajectory. At the cortical level, somatotopic organization suggests a potential underlying hodological patterning, but this has not been proven. This review describes examples of hodological patterning in motor circuits and covers current knowledge about how this patterning arises.

A novel approach to completely alleviate peripheral neuropathic pain in human patients: insights from preclinical data.

Shehab S, Hamad MIK, Emerald BS

Front Neuroanat · 2024 · PMID 39839257 · Full text

Neuropathic pain is a pervasive health concern worldwide, posing significant challenges to both clinicians and neuroscientists. While acute pain serves as a warning signal for potential tissue damage, neuropathic pain re... Neuropathic pain is a pervasive health concern worldwide, posing significant challenges to both clinicians and neuroscientists. While acute pain serves as a warning signal for potential tissue damage, neuropathic pain represents a chronic pathological condition resulting from injury or disease affecting sensory pathways of the nervous system. Neuropathic pain is characterized by long-lasting ipsilateral hyperalgesia (increased sensitivity to pain), allodynia (pain sensation in response to stimuli that are not normally painful), and spontaneous unprovoked pain. Current treatments for neuropathic pain are generally inadequate, and prevention remains elusive. In this review, we provide an overview of current treatments, their limitations, and a discussion on the potential of capsaicin and its analog, resiniferatoxin (RTX), for complete alleviation of nerve injury-induced neuropathic pain. In an animal model of neuropathic pain where the fifth lumbar (L5) spinal nerve is unilaterally ligated and cut, resulting in ipsilateral hyperalgesia, allodynia, and spontaneous pain akin to human neuropathic pain. The application of capsaicin or RTX to the adjacent uninjured L3 and L4 nerves completely alleviated and prevented mechanical and thermal hyperalgesia following the L5 nerve injury. The effects of this treatment were specific to unmyelinated fibers (responsible for pain sensation), while thick myelinated nerve fibers (responsible for touch and mechanoreceptor sensations) remained intact. Here, we propose to translate these promising preclinical results into effective therapeutic interventions in humans by direct application of capsaicin or RTX to adjacent uninjured nerves in patients who suffer from neuropathic pain due to peripheral nerve injury, following surgical interventions, diabetic neuropathy, trauma, vertebral disc herniation, nerve entrapment, ischemia, postherpetic lesion, and spinal cord injury.

The histological development of the fetal human inferior colliculus during the second trimester.

Nanda R, Bota M, Jayakumar J … +8 more , S S, Lata S, Kumar EH, Srinivasan C, Vasudevan S, Jayaraman K, Sivaprakasam M, Verma R

Front Neuroanat · 2024 · PMID 39834653 · Full text

The inferior colliculus (IC) is an important midbrain station of the auditory pathway, as well as an important hub of multisensory integration. The adult mammalian IC can be subdivided into three nuclei, with distinct cy... The inferior colliculus (IC) is an important midbrain station of the auditory pathway, as well as an important hub of multisensory integration. The adult mammalian IC can be subdivided into three nuclei, with distinct cyto- and myeloarchitectonical profiles and distinct calcium binding proteins expression patterns. Despite several studies about its structural and functional development, the knowledge about the human fetal IC is rather limited. In this paper we first systematically describe the histological development of the human fetal IC and its subparts in five stages of the second trimester of pregnancy: 15 gestation weeks (GW), 18 GW, 21 GW, 24 GW, and 27 GW. We 3D reconstruct and calculate the volumetric growth of IC from one stage to another, which increases from 12.85 mm at 15 GW to 34.27 mm at 27 GW in the left hemisphere. The volumetric changes in the IC were further evaluated at the cellular level using serial Nissl-stained sections, as well as glial fibrillary acidic proteins (GFAP) and calretinin immunohistochemistry. We identify stellate-like and round neurons in the central nucleus of the IC (CNIC) at 24 GW and 27 GW, comparable to the adult human IC. Novel in this study, we investigate the differential calretinin expression patterns in the IC subparts, from 15 GW to 27 GW. CR labeling is identified mainly in the cortical IC rather than in the central nucleus. Furthermore, using GFAP, we describe the radial glial fibers patterns in IC, which are dominant at 18 GW and gradually taper off at later developmental stages. Finally, we describe the development of astroglia in each of the five developmental stages. All these results indicate that the human fetal IC development and cellular maturation occur in two major stages during the second trimester.

Minimal differences observed when comparing the morphological profiling of microglia obtained by confocal laser scanning and optical sectioning microscopy.

Godeanu S, Mușat MI, Scheller A … +2 more , Osiac E, Cătălin B

Front Neuroanat · 2024 · PMID 39829733 · Full text

BACKGROUND: While widefield microscopy has long been constrained by out-of-focus scattering, advancements have generated a solution in the form of confocal laser scanning microscopy (cLSM) and optical sectioning microsco... BACKGROUND: While widefield microscopy has long been constrained by out-of-focus scattering, advancements have generated a solution in the form of confocal laser scanning microscopy (cLSM) and optical sectioning microscopy using structured illumination (OSM). In this study, we aim to investigate, using microglia branching, if cLSM and OSM can produce images with comparable morphological characteristics. RESULTS: By imaging the somatosensory microglia from a tissue slice of a 3-week-old mouse and establishing morphological parameters that characterizes the microglial branching pattern, we were able to show that there is no difference in total length of the branch tree, number of branches, mean branch length and number of primary to terminal branches. We did find that area-based parameters such as mean occupied area and mean surveillance area were bigger in cLSM isolated microglia compared to OSM ones. Additionally, by investigating the difference in acquisition time between techniques and personal costs we were able to establish that the amortization could be made in 6.11 ± 2.93 years in the case of countries with a Human Development Index (HDI) = 7-9 and 7.06 ± 3.13 years, respectably, for countries with HDI < 7. As such, OSM systems seem a valid option if one just wants basic histological evaluation, and cLSM should be considered for groups that demand higher resolution or volumetric images.

Cell density quantification of high resolution Nissl images of the juvenile rat brain.

Meystre J, Jacquemier J, Burri O … +7 more , Zsolnai C, Frank N, Vieira JP, Shi Y, Perin R, Keller D, Markram H

Front Neuroanat · 2024 · PMID 39744456 · Full text

Nissl histology underpins our understanding of brain anatomy and architecture. Despite its importance, no high-resolution datasets are currently available in the literature for 14-day-old rats. To remedy this issue and d... Nissl histology underpins our understanding of brain anatomy and architecture. Despite its importance, no high-resolution datasets are currently available in the literature for 14-day-old rats. To remedy this issue and demonstrate the utility of such a dataset, we have acquired over 2000 high-resolution images (0.346 μm per pixel) from eight juvenile rat brains stained with cresyl violet. To analyze this dataset, we developed a semi-automated pipeline using open-source software to perform cell density quantification in the primary somatosensory hindlimb (S1HL) cortical column. In addition, we performed cortical layer annotations both manually and using a machine learning model to expand the number of annotated samples. After training the model, we applied it to 262 images of the S1HL, retroactively assigning segmented cells to specific cortical layers, enabling cell density quantification per layer rather than just for entire brain regions. The pipeline improved the efficiency and reliability of cell density quantification while accurately assigning cortical layer boundaries. Furthermore, the method is adaptable to different brain regions and cell morphologies. The full dataset, annotations, and analysis tools are made publicly available for further research and applications.

Inhibition of neuroinflammation by GIBH-130 (AD-16) reduces neurodegeneration, motor deficits, and proinflammatory cytokines in a hemiparkinsonian model.

Bianchetti ME, Ferreira AFF, Britto LRG

Front Neuroanat · 2024 · PMID 39736920 · Full text

Parkinson's disease (PD) is a neurodegenerative condition characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) of the brain, manifesting itself with both motor and non-motor sympt... Parkinson's disease (PD) is a neurodegenerative condition characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) of the brain, manifesting itself with both motor and non-motor symptoms. A critical element of this pathology is neuroinflammation, which triggers a harmful neurotoxic cycle, exacerbating cell death within the central nervous system. AD-16 (also known as GIBH-130) is a recently identified compound capable of reducing the expression of pro-inflammatory cytokines while increasing the expression of anti-inflammatory cytokines in Alzheimer's disease models. Here, for the first time, we sought to comprehend the potential impact of orally administered AD-16 in mitigating neurodegeneration and subsequent disease progression in PD. To accomplish this, 6- hydroxydopamine (6-OHDA) unilateral striatal injections were employed to induce a PD model in male C57BL/6 mice. Cylinder and apomorphine-induced rotation behavior tests were conducted to assess motor behavior and validate the PD model 3 days after the injection. AD-16 was administered via gavage daily between days 3 and 9 after surgery. On the last day of treatment, motor tests were performed again. All animals were euthanized on day 10 and immunohistochemistry techniques were performed to detect tyrosine hydroxylase (TH) and Iba-1 and thus label dopaminergic neurons and microglia in the SNc and striatum (CPu). These same regions were collected for ELISA assays to assess different cytokine concentrations. Our results revealed an enhancement in the motor function of the AD-16-treated animals, as well as reduced nigrostriatal neurodegeneration. In addition, AD-16 reduced the increase in microglia density and prevented the changes in its morphology observed in the PD animal models. Furthermore, AD-16 was able to avoid the increase of pro-inflammatory cytokines levels that were present in 6-OHDA-injected animals who received vehicle. Consequently, AD-16 emerges as a compound with significant potential for negative modulation of neurodegeneration and neuroinflammation suppression in the 6-OHDA animal model of Parkinson's disease.

Bridging veins: an analysis of surgical anatomy and histology correlated with interhemispheric approaches.

Ye Y, Lan T, Zeng X … +5 more , Yang J, Wei R, Zhu J, Liu M, Zhu X

Front Neuroanat · 2024 · PMID 39669297 · Full text

Damage to bridging veins could lead to disastrous complications during interhemispheric approaches. We investigated the morphological and histological characteristics of bridging veins. A total of 10 cadaveric heads and... Damage to bridging veins could lead to disastrous complications during interhemispheric approaches. We investigated the morphological and histological characteristics of bridging veins. A total of 10 cadaveric heads and 86 patients were analyzed with either anatomic dissection or neuroimaging. The morphological features of the bridging veins and superior sagittal sinus were analyzed by the endoscope. The histology of the junction between the bridging veins and superior sagittal sinus was evaluated under the microscope with staining for H&E, elastic fiber, and Masson's staining. We found three types of bridging vein configurations in the junction between the bridging vein and superior sagittal sinus: direct connection (type A), vein runs a certain distance below the dural wall tightly (type B), and vein runs a certain distance on the lateral sinus (type C). Valvular-like fibrous cords were present on the opening of type A, trabecular in type B, and arachnoid granules in type C. Loose connective tissue connected the venous wall and dura mater in type A, sinus wall forms the inner wall of the bridging vein in type B, bridging vein accompanied by arachnoid granules in the type C. This classification enables surgeons to predict various bridging vein configurations, followed by safely achieving the optimal dissection during interhemispheric approaches.

Differential effects of prolonged post-fixation on immunohistochemical and histochemical staining for postmortem human brains.

Ma W, Frigon EM, Maranzano J … +2 more , Zeighami Y, Dadar M

Front Neuroanat · 2024 · PMID 39611118 · Full text

PURPOSE: Immunohistochemical (IHC) and histochemical (HC) staining techniques are widely used on human brains that are post-fixed in formalin and stored in brain banks worldwide for varying durations, from months to deca... PURPOSE: Immunohistochemical (IHC) and histochemical (HC) staining techniques are widely used on human brains that are post-fixed in formalin and stored in brain banks worldwide for varying durations, from months to decades. Understanding the effects of prolonged post-fixation, postmortem interval (PMI), and age on these staining procedures is important for accurately interpreting their outcomes, thereby improving the diagnosis and research of brain disorders afflicting millions of people worldwide. METHODS: In this study, we conducted both IHC and HC staining on the prefrontal cortex of postmortem human brains post-fixed for 1, 5, 10, 15, and 20 years. For IHC staining, we used two antibodies for each marker: the neuron marker neuronal nuclear antigen (NeuN), the astrocyte marker glial fibrillary acidic protein (GFAP), and the microglia marker ionized calcium-binding adaptor molecule 1 (Iba1). For HC staining, we conducted hematoxylin and eosin Y (H&E), cresyl violet (CV), and Luxol fast blue (LFB) stains to examine neuropils, neurons, and myelin, respectively. RESULTS: We observed that the intensity of NeuN, Iba1, CV, or LFB staining was negatively correlated with post-fixation durations. Conversely, we detected a positive correlation between the intensity of GFAP and H&E staining and post-fixation durations. Moreover, there was no correlation between the intensity of NeuN, GFAP, Iba1, H&E, CV, and LFB staining and PMI. Additionally, no correlation was found between these staining intensities and age, except for the intensity of GFAP immunostained by one antiserum, which was negatively correlated with age. CONCLUSION: Taken together, these findings suggest that prolonged post-fixation has both positive and negative effects, while age and PMI exert limited influence on these IHC and HC parameters. Therefore, it is essential to consider these differential changes when interpreting results derived from tissues with extended post-fixation durations. Furthermore, if feasible, we recommend conducting IHC and HC staining on human brains with the same post-fixation time spans and using the most optimal antibodies to mitigate the impact on subsequent analyses.

Characterization of clock proteins in the substantia nigra and subthalamic nucleus of the primate.

Guissoni Campos LM, Campanari GSDS, Santiago J … +10 more , Santos EVB, Santos ACG, Cabrini ML, Audi M, Costa IB, Evangelista de Araujo VC, Bodra SM, Gualassi MMP, Motta-Teixeira LC, Pinato L

Front Neuroanat · 2024 · PMID 39606564 · Full text

Clock genes, which are essential for suprachiasmatic nucleus (SCN) function, also play critical roles in other brain regions, and their expression have been the subject of various studies. An increasingly deeper understa... Clock genes, which are essential for suprachiasmatic nucleus (SCN) function, also play critical roles in other brain regions, and their expression have been the subject of various studies. An increasingly deeper understanding of the expression of these genes in different species contributes to our knowledge of their functions and the factors influencing their expression. Considering that most studies have been conducted in nocturnal rodents, in this study we investigated the presence of Per1, Per2 and Cry1 in neurons of the substantia nigra (SN) and subthalamic nucleus (STN) in a diurnal primate. The immunoreactivity of Per1, Per2, and Cry1 was analyzed using immunohistochemistry, revealing significant Per1-IR, Per2-IR, and Cry1-IR in the SN. While Per1-IR and Per2-IR were also observed in the STN, no Cry1-IR staining was detected in the STN. These results confirm the presence of proteins that regulate circadian rhythms in areas associated with motor behavior.

Ramón y Cajal's 'lenticular tract' represents infrasubthalamic pyramidal collaterals targeting mesodiencephalic centers: an obscure misunderstood aspect of the motor pathway clarified by Allen Mouse Brain Connectivity data.

Puelles L

Front Neuroanat · 2024 · PMID 41415035 · Full text

Ramón y Cajal repeatedly described a diencephalic tegmental tract in mammals, which he wrongly identified as corresponding to Forel's lenticular tract, while insisting it was formed by fasciculated infrasubthalamic colla... Ramón y Cajal repeatedly described a diencephalic tegmental tract in mammals, which he wrongly identified as corresponding to Forel's lenticular tract, while insisting it was formed by fasciculated infrasubthalamic collaterals of the pyramidal tract. These fibers circulated backwards between the zona incerta and the substantia nigra and were lost in the rubral neighborhood, so that their targets remained unknown. The modern literature does not register these pyramidal collaterals at all. In this report, anterograde axon-tracing experiments with motor cortex EGFP injections available at the Allen Mouse Brain Connectivity database were studied to assess whether Ramón y Cajal's collateral tract exists in the mouse and, in that case, examine the issue of its missing targets. All Allen motor cortex experiments showed straightforwardly the tract described by Ramón y Cajal, which he had lost at midcourse because it diverges into the mesodiencephalic alar plate. Moreover, it was observed to bifurcate as it enters the diencephalon into a deep medial component not distinguished by Ramón y Cajal, which targets diencephalic and mesencephalic preoculomotor cell populations and the deep ZI and Forel's field, and a thicker outer component, the part he described, which ascends through intermediate thalamic and pretectal alar structures (PIL, RETh, JcRt, and CoRt) until it ends densely on the paratectal bed nucleus of the brachium of the superior colliculus (BSC). The latter is frequently misinterpreted as a lateral part of the SC. Other midbrain targets included the rubral area, the MRt, a novel bilateral reticular endorubral field (ERF), and the preisthmic cuneiform nucleus (Cnf).

Anatomical study of single incision contralateral C7 nerve transfer through subdural pathway.

Yao L, Yan Z, Wang X … +3 more , Gu J, Liu H, Zhang H

Front Neuroanat · 2024 · PMID 39539944 · Full text

OBJECTIVE: To explore the feasibility of single incision C7 nerve transfer surgery through the subarachnoid pathway on the healthy side through anatomical research. METHOD: Four fresh frozen cadaver specimens were used f... OBJECTIVE: To explore the feasibility of single incision C7 nerve transfer surgery through the subarachnoid pathway on the healthy side through anatomical research. METHOD: Four fresh frozen cadaver specimens were used for the study. Observe and measure the length of C7 nerve root fibers. Divide the front root into 3 bundles and the rear root into 5 bundles. RESULT: The C7 nerve has a filamentous structure, arranged symmetrically on both sides, and the length of the root fibers gradually shortens from top to bottom. The length of the left anterior root decreased from (12.25 ± 0.68) mm to (9.75 ± 1.40) mm, the length of the right anterior root decreased from (12.95 ± 1.49) mm to (10.00 ± 2.00) mm, the length of the left posterior root decreased from (15.63 ± 1.55) mm to (12.38 ± 0.71) mm, and the length of the right posterior root decreased from (15.48 ± 1.37) mm to (12.30 ± 0.90) mm. The distance from the exit of the C7 nerve from the dura mater to the fusion site in 4 specimens was (10.98 ± 1.21) mm on the left and (10.98 ± 1.391) mm on the right. All four specimens have completed nerve bundle anastomosis. CONCLUSION: From an anatomical perspective, it is feasible to anastomose the healthy side C7 nerve with the affected side root fibers in the dorsal bundle of the spinal cord after cutting off the dura mater.

Parkinson's disease models and death signaling: what do we know until now?

Pedrão LFAT, Medeiros POS, Leandro EC … +1 more , Falquetto B

Front Neuroanat · 2024 · PMID 39533977 · Full text

Parkinson's disease (PD) is the second neurodegenerative disorder most prevalent in the world, characterized by the loss of dopaminergic neurons in the Substantia Nigra (SN). It is well known for its motor and non-motor... Parkinson's disease (PD) is the second neurodegenerative disorder most prevalent in the world, characterized by the loss of dopaminergic neurons in the Substantia Nigra (SN). It is well known for its motor and non-motor symptoms including bradykinesia, resting tremor, psychiatric, cardiorespiratory, and other dysfunctions. Pathological apoptosis contributes to a wide variety of diseases including PD. Various insults and/or cellular phenotypes have been shown to trigger distinct signaling events leading to cell death in neurons affected by PD. The intrinsic or mitochondrial pathway, inflammatory or oxidative stress-induced extrinsic pathways are the main events associated with apoptosis in PD-related neuronal loss. Although SN is the main brain area studied so far, other brain nuclei are also affected by the disease leading to non-classical motor symptoms as well as non-motor symptoms. Among these, the respiratory symptoms are often overlooked, yet they can cause discomfort and may contribute to patients shortened lifespan after disease diagnosis. While animal and models are frequently used to investigate the mechanisms involved in the pathogenesis of PD in both the SN and other brain regions, these models provide only a limited understanding of the disease's actual progression. This review offers a comprehensive overview of some of the most studied forms of cell death, including recent research on potential treatment targets for these pathways. It highlights key findings and milestones in the field, shedding light on the potential role of understanding cell death in the prevention and treatment of the PD. Therefore, unraveling the connection between these pathways and the notable pathological mechanisms observed during PD progression could enhance our comprehension of the disease's origin and provide valuable insights into potential molecular targets for the developing therapeutic interventions.

From Sudoscan to bedside: theory, modalities, and application of electrochemical skin conductance in medical diagnostics.

Vittrant B, Ayoub H, Brunswick P

Front Neuroanat · 2024 · PMID 39529803 · Full text

The human body has two main types of sweat glands: apocrine and eccrine. Eccrine glands are widely distributed across the skin, including areas with hair. While the eccrine glands on palms and soles help improve grip, th... The human body has two main types of sweat glands: apocrine and eccrine. Eccrine glands are widely distributed across the skin, including areas with hair. While the eccrine glands on palms and soles help improve grip, those on the rest of the body primarily aid in thermoregulation. Sudomotor function, which controls sweating, is regulated by the sympathetic division of the autonomic nervous system through cholinergic and adrenergic pathways. The activation of eccrine glands involves intricate processes, including neurotransmitter binding, ion channel modulation, and voltage generation. Sudoscan technology utilizes electrochemical skin conductance (ESC) to non-invasively measure sudomotor function. This method, which has been standardized for accuracy, has established normative benchmarks and has proven reliable across diverse populations. Sudoscan's diagnostic performance is comparable to invasive methods such as intraepidermal nerve fiber density testing, making it a valuable tool for diagnosing small fiber neuropathy. Moreover, it has been shown to correlate with corneal nerve fiber length, providing insights into various neuropathic conditions. Compared to traditional sudomotor function tests, Sudoscan proves superior in terms of its accessibility, simplicity, and reliability, with the potential to replace or complement existing diagnostic methods. It is important to differentiate ESC, as measured by Sudoscan, from other skin conductance measures, such as galvanic skin response (GSR) or electrodermal activity (EDA). Although these methods share a common physiological principle, ESC is specifically designed for diagnosing sudomotor function, unlike GSR/EDA, which is typically used for continuous monitoring. Sudoscan's success has led to its integration into consumer health devices, such as the BodyScan from Withings, showcasing its versatility beyond clinical settings. Future research may explore ESC applications in diverse medical fields, leveraging real-world data from integrated consumer devices. Collaborative efforts between researchers and engineers promise to offer new insights into sudomotor function and its implications for broader health monitoring. This study provides a comprehensive overview of ESC, including topics such as eccrine gland physiology, sudomotor function, Sudoscan technology, normative benchmarks, diagnostic comparisons, and potential future applications.

Editorial: 15 years of frontiers in neuroanatomy: the circuits behind the visual cortex.

Takahata T, Ding SL

Front Neuroanat · 2024 · PMID 39512241 · Full text

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