Frontiers in Neuroanatomy最新文献

{"title":"A novel approach to completely alleviate peripheral neuropathic pain in human patients: insights from preclinical data.","authors":"Safa Shehab, Mohammad I K Hamad, Bright Starling Emerald","doi":"10.3389/fnana.2024.1523095","DOIUrl":"https://doi.org/10.3389/fnana.2024.1523095","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"18 ","pages":"1523095"},"PeriodicalIF":2.1,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11747518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143003875","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}

{"title":"The histological development of the fetal human inferior colliculus during the second trimester.","authors":"Reetuparna Nanda, Mihail Bota, Jaikishan Jayakumar, Suresh S, S Lata, E Harish Kumar, Chitra Srinivasan, Sudha Vasudevan, Kumutha Jayaraman, Mohanasankar Sivaprakasam, Richa Verma","doi":"10.3389/fnana.2024.1502778","DOIUrl":"https://doi.org/10.3389/fnana.2024.1502778","url":null,"abstract":"<p><p>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 mm³ at 15 GW to 34.27 mm³ 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.</p>","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"18 ","pages":"1502778"},"PeriodicalIF":2.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143003877","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}

{"title":"Minimal differences observed when comparing the morphological profiling of microglia obtained by confocal laser scanning and optical sectioning microscopy.","authors":"Sânziana Godeanu, Mădălina Iuliana Mușat, Anja Scheller, Eugen Osiac, Bogdan Cătălin","doi":"10.3389/fnana.2024.1507140","DOIUrl":"https://doi.org/10.3389/fnana.2024.1507140","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Results: </strong>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.</p>","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"18 ","pages":"1507140"},"PeriodicalIF":2.1,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143003876","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}

{"title":"Cell density quantification of high resolution Nissl images of the juvenile rat brain.","authors":"Julie Meystre, Jean Jacquemier, Olivier Burri, Csaba Zsolnai, Nicolas Frank, João Prado Vieira, Ying Shi, Rodrigo Perin, Daniel Keller, Henry Markram","doi":"10.3389/fnana.2024.1463632","DOIUrl":"10.3389/fnana.2024.1463632","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"18 ","pages":"1463632"},"PeriodicalIF":2.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11688196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914332","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}

{"title":"Inhibition of neuroinflammation by GIBH-130 (AD-16) reduces neurodegeneration, motor deficits, and proinflammatory cytokines in a hemiparkinsonian model.","authors":"Maria E Bianchetti, Ana Flavia F Ferreira, Luiz R G Britto","doi":"10.3389/fnana.2024.1511951","DOIUrl":"10.3389/fnana.2024.1511951","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"18 ","pages":"1511951"},"PeriodicalIF":2.1,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11684390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906824","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}

{"title":"Bridging veins: an analysis of surgical anatomy and histology correlated with interhemispheric approaches.","authors":"Yuanliang Ye, TianCai Lan, Xiangbo Zeng, Jianqing Yang, Ruixiang Wei, Jiale Zhu, Moukun Liu, Xiaowen Zhu","doi":"10.3389/fnana.2024.1406252","DOIUrl":"10.3389/fnana.2024.1406252","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"18 ","pages":"1406252"},"PeriodicalIF":2.1,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11634616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817782","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}

{"title":"Differential effects of prolonged post-fixation on immunohistochemical and histochemical staining for postmortem human brains.","authors":"Weiya Ma, Eve-Marie Frigon, Josefina Maranzano, Yashar Zeighami, Mahsa Dadar","doi":"10.3389/fnana.2024.1477973","DOIUrl":"10.3389/fnana.2024.1477973","url":null,"abstract":"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"18 ","pages":"1477973"},"PeriodicalIF":2.1,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11602276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749663","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}

{"title":"Characterization of clock proteins in the substantia nigra and subthalamic nucleus of the <i>Sapajus apella</i> primate.","authors":"Leila Maria Guissoni Campos, Gyovanna Sorrentino Dos Santos Campanari, Jeferson Santiago, Eduardo Vinicius Barboza Santos, Alana Cristy Ghiraldelli Santos, Mayara Longui Cabrini, Mauro Audi, Isabela Bazzo Costa, Viviane Canhizares Evangelista de Araujo, Stephannie Monaco Bodra, Maressa Monteiro Pereira Gualassi, Lívia Clemente Motta-Teixeira, Luciana Pinato","doi":"10.3389/fnana.2024.1480971","DOIUrl":"10.3389/fnana.2024.1480971","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"18 ","pages":"1480971"},"PeriodicalIF":2.1,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11598418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739267","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}

{"title":"Anatomical study of single incision contralateral C7 nerve transfer through subdural pathway.","authors":"Long Yao, Zhengcun Yan, Xiaodong Wang, Jiaxiang Gu, Hongjun Liu, Hengzhu Zhang","doi":"10.3389/fnana.2024.1470913","DOIUrl":"10.3389/fnana.2024.1470913","url":null,"abstract":"<p><strong>Objective: </strong>To explore the feasibility of single incision C7 nerve transfer surgery through the subarachnoid pathway on the healthy side through anatomical research.</p><p><strong>Method: </strong>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.</p><p><strong>Result: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"18 ","pages":"1470913"},"PeriodicalIF":2.1,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142618303","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}

{"title":"Parkinson's disease models and death signaling: what do we know until now?","authors":"Luiz Fernando A T Pedrão, Pamela O S Medeiros, Estela C Leandro, Barbara Falquetto","doi":"10.3389/fnana.2024.1419108","DOIUrl":"https://doi.org/10.3389/fnana.2024.1419108","url":null,"abstract":"<p><p>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 <i>in vitro</i> 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.</p>","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"18 ","pages":"1419108"},"PeriodicalIF":2.1,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617029","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}