Frontiers in NeuroanatomyPub Date : 2026-04-10eCollection Date: 2026-01-01DOI: 10.3389/fnana.2026.1801873
Mohammed M Nakhal, Faheema Nafees, Ayishal B Mydeen, Abdulaziz Al Ali, Sarah Baloch, Rawdha Alkhalaf, Hasan M Albalas, Ghassan M Albalas, Gadayer Alharbi, Yauhen Statsenko, Nour Al-Dain Marzouka, Mohammad I K Hamad
{"title":"Maternal gut dysbiosis is associated with altered enteric and cortical inhibitory circuit development.","authors":"Mohammed M Nakhal, Faheema Nafees, Ayishal B Mydeen, Abdulaziz Al Ali, Sarah Baloch, Rawdha Alkhalaf, Hasan M Albalas, Ghassan M Albalas, Gadayer Alharbi, Yauhen Statsenko, Nour Al-Dain Marzouka, Mohammad I K Hamad","doi":"10.3389/fnana.2026.1801873","DOIUrl":"https://doi.org/10.3389/fnana.2026.1801873","url":null,"abstract":"<p><strong>Introduction: </strong>Maternal environmental factors critically influence neural circuit maturation during early development. The maternal gut microbiota has emerged as an important upstream regulator of offspring neurodevelopment, yet its role in shaping the structural organization of enteric and cortical inhibitory circuits remains poorly defined. Here, we examined whether gestational disruption of the maternal gut microbiota is associated with alterations in parallel enteric and cortical inhibitory circuit development.</p><p><strong>Methods: </strong>Maternal gut dysbiosis was induced in pregnant GAD67-GFP mice by oral vancomycin administration during gestation. Maternal and offspring microbiota were analyzed using full-length 16S rRNA gene sequencing to assess microbial diversity and vertical transmission. Offspring were examined at postnatal day 14 for intestinal morphology, altered barrier integrity, and enteric nervous system (ENS) organization. Cortical inhibitory circuits were analyzed by quantifying GAD67-positive interneuron density and performing three-dimensional morphological reconstruction in layers II/III of the somatosensory cortex, motor cortex, medial entorhinal cortex, and CA1 region of the hippocampus.</p><p><strong>Results: </strong>Maternal dysbiosis significantly reduced microbial diversity and disrupted maternal-offspring microbial transmission. These changes were associated with impaired intestinal development, including reduced crypt height, thinning of the muscularis propria, fragmented Claudin-1 expression, and reduced Auerbach's plexus area without changes in neuronal density, indicating altered enteric network organization. In the brain, maternal dysbiosis induced region-specific cortical vulnerability, with reduced dendritic length and branching of GAD67-positive interneurons in the somatosensory and motor cortices, while interneuron morphology in the medial entorhinal cortex and hippocampus was preserved. Interneuron density was selectively reduced in the motor cortex.</p><p><strong>Discussion: </strong>These findings indicate that gestational maternal dysbiosis is associated with co-occurring structural alterations in intestinal and cortical inhibitory systems, selectively affecting inhibitory circuit architecture in sensorimotor regions. While the present model does not isolate microbiota-specific mechanisms from potential antibiotic-induced maternal physiological changes, the data support an association between disrupted maternal microbial ecology and offspring enteric and cortical neuroanatomical development during early postnatal life. These findings should be interpreted as descriptive associations and do not establish mechanistic gut-brain interactions.</p>","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"20 ","pages":"1801873"},"PeriodicalIF":2.3,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13106469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147768915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in NeuroanatomyPub Date : 2026-04-10eCollection Date: 2026-01-01DOI: 10.3389/fnana.2026.1748518
Marwa Abd El-Kader, Eman A E Farrag, Randa El-Gamal, Eman Mohamed El Nashar, Areej M Alshehri, Rashid A Aldahhan, Khulood M Al-Khater, Sara El-Desouky, M W El-Sherbeni, Neven A Ebrahim
{"title":"Folic acid modulates the Notch1/NF-κB pathway in a rat model of lipopolysaccharide-activated hippocampal microglia.","authors":"Marwa Abd El-Kader, Eman A E Farrag, Randa El-Gamal, Eman Mohamed El Nashar, Areej M Alshehri, Rashid A Aldahhan, Khulood M Al-Khater, Sara El-Desouky, M W El-Sherbeni, Neven A Ebrahim","doi":"10.3389/fnana.2026.1748518","DOIUrl":"https://doi.org/10.3389/fnana.2026.1748518","url":null,"abstract":"<p><strong>Introduction: </strong>Lipopolysaccharide (LPS) induces neuronal injury by stimulating microglia, which release pro-inflammatory markers and neurotoxic factors. Folate deficiency induces microglial activation and modulates nuclear factor-κB (NF-κB) p65 and neurogenic locus Notch homolog protein 1 (Notch1) expression in the hippocampus. This study investigated the neuroprotective effect of folic acid against LPS-induced neurotoxicity in rats, focusing on its modulation of microglial activation and the Notch1, NF-κB, and p65 signaling pathways.</p><p><strong>Methods: </strong>A total of 24 Sprague-Dawley male rats were assigned to four groups: control, folic acid, LPS, and folic acid + LPS. After sacrifice, the left cerebral hemisphere was subjected to histopathological assessment using hematoxylin and eosin (H&E) staining and immunohistochemical assessment using anti-GFAP, anti-Iba1, anti-cyclooxygenase-2 (COX-2), anti-tumor necrosis factor-<i>α</i> (TNF-α), and anti-NF-κB antibodies. The hippocampus was extracted from the right hemisphere and used to assess the gene expression of Notch1, TNF-α, interleukin-6 (IL-6), and COX-2 markers using real-time reverse transcription PCR.</p><p><strong>Results: </strong>Folic acid ameliorated LPS-induced neuronal damage in the hippocampus, suppressed microglial activation (GFAP and Iba-1), downregulated Notch1 and NF-κB p65, and improved neuroinflammatory responses (TNF-α, IL-6, and COX-2), regardless of the region.</p><p><strong>Conclusion: </strong>Folic acid exerted an equivalent neuroprotective effect in both the CA1 and CA3 regions by suppressing microglial activation and modulating the Notch1/NF-κB signaling pathway, thereby reducing neuroinflammation. These findings suggest that folic acid may serve as a potential adjuvant neuroprotective agent against inflammation-mediated neuronal injury.</p>","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"20 ","pages":"1748518"},"PeriodicalIF":2.3,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13107479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147768950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in NeuroanatomyPub Date : 2026-04-10eCollection Date: 2026-01-01DOI: 10.3389/fnana.2026.1768036
Yun Xing, Jiaxin Liu, Linrui Wu, Ke Zhang, Shengbo Yang
{"title":"A narrative review of motor control dual pathways: the corticospinal and reticulospinal tracts in synergy and differentiation.","authors":"Yun Xing, Jiaxin Liu, Linrui Wu, Ke Zhang, Shengbo Yang","doi":"10.3389/fnana.2026.1768036","DOIUrl":"https://doi.org/10.3389/fnana.2026.1768036","url":null,"abstract":"<p><p>The corticospinal tract (CST) and reticulospinal tract (RST) represent the core descending pathways within the central nervous system for motor control. This review elucidates the anatomical and functional interplay. Anatomically, the CST and RST fibers are spatially proximate within the spinal cord and are integrated into a continuous regulatory axis via the corticoreticular pathway. Functionally, they exhibit both synergy and specialization: the CST primarily governs contralateral distal limb fine motor control, whereas the RST, operating in a bilateral mode, regulates axial and proximal body movements, postural stability, and adaptation to strength training. Notably, following CST damage (e.g., stroke or spinal cord injury), the RST demonstrates remarkable plasticity and serves as a critical substrate for functional compensation and recovery. Furthermore, an imbalance in CST-RST function has been implicated in the pathophysiology of conditions such as post-stroke spasticity and multiple sclerosis. Therapeutic strategies targeting the CST-RST network, including neuromodulation and molecular interventions aimed at promoting axonal regeneration and modulating network excitability, present promising new directions for the treatment of neurological disorders. Future research should focus on deciphering the specific interactions at the spinal interneuron level to advance the development of precise rehabilitation strategies.</p>","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"20 ","pages":"1768036"},"PeriodicalIF":2.3,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13106552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147768901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in NeuroanatomyPub Date : 2026-04-08eCollection Date: 2026-01-01DOI: 10.3389/fnana.2026.1749231
Jian Qi, Chen Chen, Qian Gao
{"title":"The effect of complex double-axis rotation model on GABAergic neurons in caudal ventrolateral medulla of rats along the vestibulo-sympathetic reflex pathway.","authors":"Jian Qi, Chen Chen, Qian Gao","doi":"10.3389/fnana.2026.1749231","DOIUrl":"https://doi.org/10.3389/fnana.2026.1749231","url":null,"abstract":"<p><strong>Introduction: </strong>Motion sickness is a common physiological disorder induced by with unusual movement exposure, characterized by conflicting motion signals that trigger vestibulo-sympathetic reflexes (VSR). These reflexes mediate autonomic responses to motion-induced stress. Previous studies have implicated the vestibular nucleus complex and the caudal ventrolateral medulla (CVLM) in VSR modulation. GABA (γ-aminobutyric acid), the primary inhibitory neurotransmitter in the central nervous system (CNS), plays a key role in both cardiovascular regulation and vestibular function. However, the specific contribution of GABAergic structures to motion sickness-related cardiovascular responses remains unclear.</p><p><strong>Methods: </strong>In this study, we combined retrograde tracing and immunofluorescence labeling to investigate GABAergic pathways using complex double-axis rotation model. Fluoro-Gold (FG) was injected into the CVLM, while biotinylated dextran amine (BDA) was delivered to the medial vestibular nuclei (MVe).</p><p><strong>Results: </strong>Our results revealed a bilateral distribution of GABAergic neurons, predominantly within the caudal raphe nuclei. Notably, a subset of these neurons was activated (as indicated by Fos immunoreactivity) and projected to the CVLM (as shown by retrograde labeling with FG) under complex double-axis rotation model. Furthermore, these same neurons also received direct inputs from the MVe, as evidenced by their labeling with BDA.</p><p><strong>Discussion: </strong>Our findings offer morphological evidence that GABAergic neurons in the caudal raphe nuclei participate in the cardiovascular responses evoked by motion sickness in a complex double-axis rotation model.</p>","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"20 ","pages":"1749231"},"PeriodicalIF":2.3,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13099919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147768869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in NeuroanatomyPub Date : 2026-03-30eCollection Date: 2026-01-01DOI: 10.3389/fnana.2026.1779669
Yong-Shin Hong, Young-Seok Park
{"title":"Neuroanatomical organization: the palato-pharyngeal complex as a sensory-motor hub.","authors":"Yong-Shin Hong, Young-Seok Park","doi":"10.3389/fnana.2026.1779669","DOIUrl":"https://doi.org/10.3389/fnana.2026.1779669","url":null,"abstract":"<p><p>The pharynx has traditionally been described as a musculo-membranous conduit involved in respiration and deglutition. From a neuroanatomical perspective, however, this region also represents a multi-nerve interface where somatic afferents of the trigeminal nerve (V) and visceral afferents of the glossopharyngeal (IX) and vagus (X) nerves converge. In this review, we use the term Palato-Pharyngeal Complex (PPC) to describe this anatomically integrated region and discuss its potential role as a sensory-motor interface associated with brainstem circuits involving the nucleus tractus solitarius (NTS) and nucleus ambiguus (NA). We highlight the coordinated activity of the tensor veli palatini (innervated by V3) and the levator veli palatini (innervated by X) as an example of somatic-visceral motor integration within this region. Building on existing models of brainstem central pattern generators, we discuss a hierarchical control framework in which brainstem circuits may be modulated by supranuclear influences from cortical and limbic systems. Within this context, we introduce the concept of a Reflex-Volition Coupling (RVC) zone as a possible functional interface between reflexive brainstem rhythms and volitional or affective control. By integrating comparative and connectomic perspectives, this review outlines how branchial motor circuitry may support a range of behaviors including airway protection, vocalization, and speech. Together, these observations suggest that the PPC may represent an anatomically strategic interface linking peripheral cranial nerve afferents with brainstem integrative networks involved in arousal and behavioral coordination. This framework provides a basis for future studies exploring how oropharyngeal sensory pathways interact with central neural circuits.</p>","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"20 ","pages":"1779669"},"PeriodicalIF":2.3,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13071065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147689432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in NeuroanatomyPub Date : 2026-03-27eCollection Date: 2026-01-01DOI: 10.3389/fnana.2026.1778296
Sandra Isabel Marques, Helena Carmo, Félix Carvalho, João Pedro Silva, Susana Isabel Sá
{"title":"A semi-automated pipeline integrating ImageJ/Fiji and StarDist for the reproducible quantification of cellular and optical density metrics in immunofluorescence images of brain tissue.","authors":"Sandra Isabel Marques, Helena Carmo, Félix Carvalho, João Pedro Silva, Susana Isabel Sá","doi":"10.3389/fnana.2026.1778296","DOIUrl":"https://doi.org/10.3389/fnana.2026.1778296","url":null,"abstract":"<p><p>Quantitative immunofluorescence is widely used to assess molecular expression and cellular distribution across biological tissues, yet the analysis of large image datasets remains time-consuming and prone to user-dependent variability. To address these limitations, we herein developed a semi-automated workflow that integrates ImageJ/Fiji for image processing, StarDist for nuclear segmentation, and spreadsheet- or Python-based routines for data curation. The pipeline standardizes critical analytical steps, including scale calibration, region-of-interest (ROI) definition, channel selection, and z-stack handling, while preserving essential metadata through a structured file-naming system. Optical density and cell-number metrics are exported automatically in a consistent format, enabling efficient consolidation into a unified dataset. Subsequent curation can be performed either manually in a spreadsheet software or fully automatically through custom Python scripts, allowing extraction of sample identifiers, regions, and markers, as well as calculation of normalized intensity values. Comparison with existing protocols proved that this workflow adheres to widely accepted quantification principles while markedly improving reproducibility, consistency, and analytical throughput. This method offers a straightforward, transparent, and scalable solution for fluorescence-based quantification suitable for laboratories with varying levels of computational expertise.</p>","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"20 ","pages":"1778296"},"PeriodicalIF":2.3,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13066318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147672420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in NeuroanatomyPub Date : 2026-03-18eCollection Date: 2026-01-01DOI: 10.3389/fnana.2026.1754934
Isabel Gonzalo-Fonrodona
{"title":"Justo Gonzalo (1910-1986): a pioneer of brain dynamics.","authors":"Isabel Gonzalo-Fonrodona","doi":"10.3389/fnana.2026.1754934","DOIUrl":"https://doi.org/10.3389/fnana.2026.1754934","url":null,"abstract":"<p><p>The present work offers an overview of the pioneering contributions of the neuroscientist Justo Gonzalo to the study of the human cerebral cortex, within the historical context of his time and in relation to current research. Gonzalo initially trained under Gonzalo Rodríguez Lafora (a disciple of Santiago Ramón y Cajal) and always maintained a close relationship with him and his circle, connecting him to the Spanish Neurological School (Cajal's school). He also trained in neurology in Austria and Germany (1933-1935). The research he called <i>brain dynamics</i> began during the Spanish Civil War (1936-1939) in a military hospital in Valencia, based on the study of patients with war-related brain injuries. Based on physiological criteria, Gonzalo described what he termed <i>central syndrome</i> of the cortex: a multisensory and bilaterally symmetrical disorder caused by a unilateral parieto-occipital cortical lesion in an associative area. He brought to light singular perceptual phenomena, and was the first to study inverted or tilted perception (visual, tactile, and auditory), the improvement of perception through increased stimulus intensity or the presence of additional stimuli, as well as other phenomena that remain little known today. These findings and the study of different cortical syndromes led Gonzalo to propose that the specificity of brain functions is gradually distributed throughout the cerebral cortex, giving rise to cortical gradients, whose overlap would result in fairly nonspecific or multisensory adaptive regions. This unitary approach went beyond the rigid cortical parcellation for the anatomical localization of brain functions, and is closely aligned with current studies. The interpretation of the <i>central syndrome</i> as analogous to the normal case, but with reduced excitability, led Gonzalo to apply scaling concepts that enabled him to develop formalizations and generalizations. He conducted this research in Spain, under very difficult conditions, with the support of the Cajal Institute. Despite the excellent international reception of his works in Spanish during the 1940s and 1950s, his contributions are scarcely known today due to the lack of timely publications in other languages. The publication of his works in English in 2023 has partially filled this gap.</p>","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"20 ","pages":"1754934"},"PeriodicalIF":2.3,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13038907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147608670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in NeuroanatomyPub Date : 2026-03-11eCollection Date: 2026-01-01DOI: 10.3389/fnana.2026.1783101
Eriko Fujita-Jimbo, Genri Kawahara, Takashi Momoi
{"title":"Foxp2 mutations and abnormal brain and gastrointestinal development: insights from animal models of speech-language and autism spectrum disorders.","authors":"Eriko Fujita-Jimbo, Genri Kawahara, Takashi Momoi","doi":"10.3389/fnana.2026.1783101","DOIUrl":"10.3389/fnana.2026.1783101","url":null,"abstract":"<p><p>Autism spectrum disorder (ASD) and speech and language disorder (SLD) are distinct neurodevelopmental conditions, yet both share overlapping communication impairments. <i>Forkhead box P2</i> (<i>FOXP2</i>), a key transcription factor involved in speech and language development, harbors pathogenic mutations such as R553H, which cause SLD and have been suggested to contribute to aspects of ASD-related phenotypes. This review synthesizes insights from animal models to explore the molecular mechanisms by which <i>Foxp2</i> mutations disrupt the development of the cerebral cortex, thalamus, and enteric nervous system. We highlight findings from heterozygous <i>Foxp2</i> mutants and discuss severe phenotypes observed in homozygous <i>Foxp2</i> mutants (<i>Foxp</i>2<sup>R552H/R552H</sup> and <i>Foxp</i>2<sup>R552H/R552H</sup>/mCherry-Tg mice), including profound ultrasonic vocalization deficits, brain malformations, and early lethality. Notably, these mice exhibit gastrointestinal abnormalities involving the epithelium, smooth muscle, and enteric nervous system, which are linked to impaired autoregulation and interference with Wnt signaling during development. Such observations underscore the relevance of the brain-gut-microbiome axis and Hirschsprung-like pathology in neurodevelopmental disorders. Finally, this review discusses future directions using gene-editing approaches in non-mammalian models-zebra finches, zebrafish, and <i>Drosophila</i>-to dissect neural networks underlying intellectual disability and communication deficits. Collectively, these studies provide a framework for understanding <i>FOXP2</i>-related molecular mechanisms in the pathogenesis of ASD and SLD.</p>","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"20 ","pages":"1783101"},"PeriodicalIF":2.3,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13013429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147520745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers in NeuroanatomyPub Date : 2026-03-10eCollection Date: 2026-01-01DOI: 10.3389/fnana.2026.1768392
Maria M O Azambuja, Nelyane N M de Santana, Paulo L A G Morais, Gabriel A M Vasiljevic, Jeferson S Cavalcante, Adhil Bhagwandin, José R L P Cavalcanti, Rovena Clara Engelberth
{"title":"Age-related dopaminergic integrity in the SNpc and VTA: morphometric and volumetric findings in marmoset (<i>Callithrix jacchus</i>).","authors":"Maria M O Azambuja, Nelyane N M de Santana, Paulo L A G Morais, Gabriel A M Vasiljevic, Jeferson S Cavalcante, Adhil Bhagwandin, José R L P Cavalcanti, Rovena Clara Engelberth","doi":"10.3389/fnana.2026.1768392","DOIUrl":"10.3389/fnana.2026.1768392","url":null,"abstract":"<p><p>Given a convergence of evidence indicating age-related vulnerability in nuclei associated with basal ganglia circuits, understanding the pattern of normal aging in non-human primates is essential for basic and applied research. To address this, we examined the age-dependent vulnerability of dopaminergic cells in the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA) of marmoset through morphoquantitative analysis of cytoarchitecture. Thus, we selected brain tissue from adult and aged marmosets processed for tyrosine hydroxylase (TH) immunohistochemistry. We estimated regional volume and counted TH-immunopositive (TH<sup>+</sup>) neurons in the SNpc and VTA. Statistical comparisons used permutation tests and Spearman's tests to analyze differences between age groups. Although Spearman's correlation test showed a negative correlation between regional volume and age and between TH<sup>+</sup> cell number and age, no significant differences were found in either the permutation test or Spearman's correlation for TH + neuronal number and for regional volume between the age groups for both nuclei. We concluded that aging in marmosets does not lead to significant loss of dopaminergic neurons or measurable volumetric reduction in the SNpc or VTA. Our results highlight the importance of understanding physiological aging in contrast to models characterized by structural degeneration, such as those found in pathological conditions. Understanding, in a promising experimental model as marmoset, the pattern of vulnerability and resilience of dopaminergic regions fills gaps in the literature and opens avenues for understanding molecular and functional changes related to aging.</p>","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"20 ","pages":"1768392"},"PeriodicalIF":2.3,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13008971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147511392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}