Developmental Neuroscience最新文献

{"title":"Spatiotemporal Characterisation of Key Cortical Developmental Markers in the Developing Ferret Brain.","authors":"Rylie-May Alexa Hickmott, Mikaela Barresi, Abdulhameed Bosakhar, Sebastian Quezada, Anita Quigley, David W Walker, Mary Tolcos","doi":"10.1159/000547661","DOIUrl":"10.1159/000547661","url":null,"abstract":"<p><strong>Introduction: </strong>The ferret is an important model for studying corticogenesis and cortical gyrification due to its small size, condensed cortical development timeline, and postnatal onset of gyrification. Its cortical progenitor and neuronal diversity closely resemble those of humans. However, detailed histological data across the rostrocaudal axis at critical embryonic and postnatal stages remain limited, particularly for recently identified progenitor subpopulations. This study aimed to comprehensively characterise the spatiotemporal expression of key progenitor and neuronal markers throughout the rostrocaudal axis of the developing ferret cortex at critical embryonic and postnatal ages. In doing so, the study sought to establish a foundational, descriptive atlas of neurodevelopmental marker expression across key time points and cortical regions and layers.</p><p><strong>Methods: </strong>Immunofluorescent labelling of key neural progenitor and neuronal markers was performed on coronal ferret brain sections at embryonic (E34, E38) and postnatal (P2, P5, P15, P25) ages. Markers included PAX6, SOX2, TBR2, HOPX, CPLX3, CTIP2, SATB2, TUJ1, and DCX. Semi-quantitative analyses described the spatiotemporal distribution of each marker within defined cortical compartments along the rostrocaudal axis.</p><p><strong>Results: </strong>Early radial glial markers PAX6 and SOX2 were abundant in the ventricular zone at embryonic stages, progressively declining postnatally as the subventricular zone (SVZ) expanded. Intermediate progenitor cells labelled by TBR2 showed high abundance in the SVZ prenatally, with a marked decrease after birth. HOPX identified outer radial glia populations exhibiting distinct temporal and spatial distributions, with increasing presence in the subplate (SP) and cortical plate during postnatal stages. CPLX3 expression emerged postnatally, delineating mature SP neurons with regionally patterned maturation. Deep- and superficial-layer neuronal markers CTIP2 and SATB2 displayed orderly laminar emergence, indicating progressive cortical layer formation. General neuronal markers TUJ1 and DCX highlighted the maturation and migration of post-mitotic neurons, with spatiotemporal gradients reflecting cortical differentiation across regions.</p><p><strong>Conclusion: </strong>This detailed profiling fills critical gaps in the ferret histological record and serves as a valuable resource for investigations into mammalian corticogenesis using the ferret model. Through the integration of semi-quantitative assessments and qualitative analysis, this dataset contributes to the ongoing development of a detailed atlas of ferret brain development. These findings are expected to enhance the utility of the ferret model in neurodevelopmental research, particularly in translational contexts involving human cortical malformations.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"293-313"},"PeriodicalIF":2.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144745798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Six Hours of Hydrogen Gas Inhalation Has a Neuroprotective Effect Even in Piglets with Delayed Functional Recovery.","authors":"Eri Inoue, Shinji Nakamura, Yuichiro Sugiyama, Toui Tsuchiya, Yasuhiro Nakao, Tsutomu Mitsuie, Takayuki Yokota, Kosuke Sakamoto, Kota Inoue, Yinmon Htun, Aya Morimoto, Ken-Ichi Ohta, Hirosuke Morita, Sonoko Kondo, Kosuke Koyano, Aya Tanaka, Takanori Miki, Masaki Ueno, Takashi Kusaka","doi":"10.1159/000546831","DOIUrl":"10.1159/000546831","url":null,"abstract":"<p><strong>Introduction: </strong>Combined therapeutic hypothermia (TH) and 24-h hydrogen (H₂) gas inhalation reduces seizure burden in piglets in the latent phase of hypoxic-ischemic (HI) injury versus TH alone. Nevertheless, the effects of H₂ gas in the earliest phase following resuscitation were unclear.</p><p><strong>Methods: </strong>After HI insult, 17 piglets ≤24 h old were divided into a HI insult group (HI, n = 8) and a HI and H₂ gas group (HI-H₂, 2.1%-2.7% H₂ gas, 6 h, n = 9). Time to recovery to a normal amplitude-integrated electroencephalogram background (RT-aEEG) was examined for 6 h after HI insult and undamaged neurons were counted.</p><p><strong>Results: </strong>The duration of low-amplitude (<5 μV) EEG after insult was not different between the two groups. Undamaged neuron numbers were significantly higher in the HI-H₂ group than in the HI group (p < 0.01), although RT-aEEG was not different.</p><p><strong>Conclusion: </strong>Six hours of H₂ gas inhalation initiated from resuscitation significantly increased the number of undamaged neurons compared to the untreated group, although there was no difference in RT-aEEG. Six hours of hydrogen gas inhalation exerts a neuroprotective effect even in piglets with delayed functional recovery.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"271-281"},"PeriodicalIF":2.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developmental Progression of Inhibitory Control and Flexible Problem-Solving among Infants with Histories of Preterm Birth.","authors":"Srishti Jayakumar, Ezequiel Ramos, Kathryn A Carson, Krysten Garcia, Katherine M Raja, Natasha N Ludwig, Ananya Sarkar, Lauren L Jantzie, Shenandoah Robinson, Marilee C Allen, V Joanna Burton, Gwendolyn Gerner","doi":"10.1159/000546746","DOIUrl":"10.1159/000546746","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Inhibitory control during visually guided reaching allows for the development of flexible problem-solving in healthy infants born at term. Inhibitory control is often impaired among older children born preterm, but the developmental trajectory of inhibitory control in infants born preterm is not well understood. The objective of this study was to evaluate the developmental trajectory of inhibitory control on the Object Retrieval Task in infants born preterm.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This was a cross-sectional study including a convenience sample of infants born preterm (less than 37 weeks), who were evaluated at corrected ages 5-6, 7-8, 9-10, 11-12, 13-15, and 16-18 months. Children born preterm with additional diagnoses of congenital anomalies, known genetic disorders, focal stroke, neoplasm, or maternal HIV exposure or children in the care of the state were excluded. Children in each of the age-groups were asked to retrieve a toy from a Plexiglas box with an opening on one side. The orientation of the opening was rotated over three trials, and the visually guided reach patterns were scored based on methods used by Diamond. Visually guided reach patterns ranged from perseverative hitting of the box to immediately reaching through the box opening. Analysis consisted of Fischer's exact tests to compare categorical measures, Jonckheere-Terpstra tests to compare ordinal measures, F test from general linear models to compare continuous measures and ordinal logistic regression to assess the association between brain injury and reach patterns.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The majority of infants born preterm in corrected age-groups of 5-6, 7-8, and 9-10 months perseveratively hit the box regardless of the orientation of the opening. This pattern of predominant immature visually guided reaching persisted at 12 months corrected age in this cohort of infants born preterm, with 75% participants demonstrating an immature reach with the box opening at the front and to the left and 88% demonstrating this with the box opening to the right.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;In this cohort of preterm infants, developmental progression of inhibitory control and progression of visually guided reaching did not follow the same developmental trajectory observed in full term typically developing infants previously documented by Diamond (1994). While 100% of typically developing infants born at term in Diamond's cohort demonstrated inhibitory control and mature visually guided reach patterns by age 12 months, 75% of participants in our cohort of infants born preterm continued to demonstrate a predominance of immature visually guided reach patterns. This study demonstrates identification of early impairments in inhibitory control using a resource-conscious, low-cost, and brief neurobehavioral assessment tool. This provides a window for early interventions to limit problems in executive dysfunction at school age and beyond.&lt;/","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"193-203"},"PeriodicalIF":2.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12280834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267805","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":"Chorioamnionitis Induces a Unique Time Course of Inflammatory Changes and Immune Reponses in the Brain and Spleen.","authors":"Maide Ozen, Alexandria Vergara, Yuma Kitase, Balaji Vijayakumar, Aidan Perales, Shenandoah Robinson, Lauren L Jantzie","doi":"10.1159/000546624","DOIUrl":"10.1159/000546624","url":null,"abstract":"<p><strong>Introduction: </strong>Inflammatory oxidative microenvironments can alter heme oxygenase-1 (HO-1) homeostasis. Dysregulation of HO-1 favors proinflammatory signals, while transferrin receptor 1 (TfR1) regulates anti-inflammatory signal transduction. Previously, we have shown that chorioamnionitis (CHORIO) induces sustained elevations in HO-1/TfR1 at postnatal day (P)2 and mononuclear cell-driven inflammation at term age equivalent P7. Here, we hypothesized that an altered HO-1/TfR1 developmental time course would coincide with inflammatory/immune signal changes in the brain.</p><p><strong>Methods: </strong>To induce CHORIO in rats, we performed a laparotomy followed by bilateral transient uterine artery occlusion and intra-amniotic injection of lipopolysaccharide (LPS) at E18. The control group received laparotomy only with equivalent duration of anesthesia. We used real-time polymerase chain reaction (RT-PCR), multiplex electrochemiluminescent immunoassay (MECI), and flow cytometry (FC) to study changes in pro- and anti-inflammatory gene expression, immune cell secretome, and immune cells at critical and clinically relevant timepoints following CHORIO.</p><p><strong>Results: </strong>We found an acute reduction in anti-inflammatory signals in the cortex on embryonic day (E)19. This was followed by an increased proinflammatory signature on postnatal day (P)2. There were also significant alterations in the phenotypic distribution of splenic T cells on P7, a key organ in immune function. Furthermore, we showed that the microenvironment of the cortex at P21 was skewed toward a proinflammatory state by significant increases in IL-6. The prominence of T-helper cells (Th) in brain concomitant with a proinflammatory state at P21 suggests emerging inflammation and potential for neural injury.</p><p><strong>Conclusions: </strong>Defining how these and other inflammatory/immune signatures contribute to perinatal brain injury and investigating distinct immune signatures at more developmental time courses will be beneficial for targeting emerging therapies.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"167-181"},"PeriodicalIF":2.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12281413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200743","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":"Association between Cold-Inducible RNA-Binding Motif 3 and Hypothermia Effect in Murine Hypoxia-Ischemia Model Measured by Hyperpolarized ¹³C MRI.","authors":"Xiaodan Liu, Xiangning Jiang, Alkisti Mikrogeorgiou Capper, Nicholas Stewart, Will Byrne, Xiao Ji, Jacob Ellison, Duan Xu, Donna M Ferriero","doi":"10.1159/000548626","DOIUrl":"10.1159/000548626","url":null,"abstract":"<p><strong>Introduction: </strong>The efficacy of therapeutic hypothermia (TH) for neonatal hypoxic-ischemic encephalopathy (HIE) is inconsistent, and the cause remains unclear. This study aimed to explore the role of cold stress protein in the TH-induced neuroprotection following hypoxia-ischemia (HI) using hyperpolarized carbon-13 MRI (HP-13C MRI).</p><p><strong>Methods: </strong>Postnatal day 10 (P10) mice underwent unilateral HI followed by treatments with TH or normothermia (NT). HI and sham mice were scanned at 4 h and 22 h following TH after injection of hyperpolarized 13C-1 labeled pyruvate. The dynamic HP [1-13C] MR spectroscopic images (MRSI) were acquired to examine the cerebral metabolic profile, i.e., the conversion rate from pyruvate to lactate (k_PL) and the ratio of lactate to pyruvate (Lac/Pyr) in the injured hemisphere. T2-weighted images and diffusion MR images were acquired to identify the anatomical structures and assess the injury. Mice brains were collected during and at 0 h, 4 h, 12 h, 18 h, and 22 h after treatments for Western Blot to investigate the time course of the levels of the cold stress protein (RNA-binding motif 3 [RBM3]) and cell death markers (spectrin 145/150 and spectrin 120) changes. The cerebral metabolic profile, RBM3 and spectrin levels, and injury size were compared across groups and between specific timepoints. The relationship between the cerebral metabolic profile and RBM3 levels in HI+TH group was also evaluated.</p><p><strong>Results: </strong>We observed the upregulation of RBM3 during TH at 4 h and 22 h after TH. The spectrin 145/150 and spectrin 120 were unchanged over time in HI+TH group, whereas they significantly increased at 18 h and 22 h in HI+NT group. Additionally, the injury size was noticeably larger at 22 h in HI+NT group. Lower k_PL and Lac/Pyr were observed at 4 h and 22 h after TH, with a negative correlation to RBM3 levels in HI+TH group.</p><p><strong>Conclusion: </strong>This study demonstrates that RBM3 may be one of the key factors associated with TH-induced neuroprotection by reducing the anaerobic glycolysis process in HI mice, suggesting RBM3 upregulation may enhance the efficacy of TH for neonatal HIE.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"398-410"},"PeriodicalIF":2.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12659713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145151627","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":"Association of Umbilical Cord Blood Serotonin Levels with Neurodevelopmental Outcomes.","authors":"Kally C O Apos Reilly Sparks, Lauren C Shuffrey, Rebecca N Siegel, Hannah Yueh, Morgan R Firestein, Amy J Elliott, Hein J Odendaal, George M Anderson, William P Fifer, Jeremy Veenstra-VanderWeele","doi":"10.1159/000547803","DOIUrl":"10.1159/000547803","url":null,"abstract":"<p><strong>Introduction: </strong>Serotonin (5-hydroxytryptamine [5-HT]) plays an important role in early development, and fetal 5-HT has been reported to arise from placental and maternal sources. Previous human studies have established an association between maternal 5-HT levels and neurodevelopmental outcomes in populations with autism. In this study, we analyze umbilical cord blood and placental 5-HT levels at birth to further investigate the relationship of gestational 5-HT levels with birth outcomes and offspring cognitive development.</p><p><strong>Methods: </strong>Participants were enrolled in the Safe Passage Study conducted by the Prenatal Alcohol and SIDS and Stillbirth (PASS) Network. Infant cord blood and placental samples were collected postdelivery, and 5-HT levels were measured using high-performance liquid chromatography-fluorometric analysis. The Mullen Scales of Early Learning (MSEL) assessed child development at 12 months. Associations between 5-HT levels and birth outcomes or developmental outcomes were assessed using linear regression models.</p><p><strong>Results: </strong>No significant association was found between cord blood (n = 418) and placental (n = 89) 5-HT levels. Preterm birth was associated with lower cord blood 5-HT levels, and increasing gestational age among full-term infants was associated with higher cord blood 5-HT levels. Cord blood 5-HT was significantly associated with the Mullen Scales of Early Learning Composite Score, and follow-up analyses revealed a significant association between cord blood 5-HT and fine motor skills. No association was found between placental 5-HT and the Mullen composite score.</p><p><strong>Conclusion: </strong>To our knowledge, this study is the first to evaluate the relationship between placental 5-HT levels and cord blood 5-HT levels at birth. The lack of association suggests that cord blood 5-HT levels are likely to be a better index of fetal 5-HT exposure. Associations between cord blood 5-HT and child cognitive development are consistent with previous studies showing an association between maternal 5-HT levels and neurodevelopmental trajectories. Further research is needed to better characterize these relationships and to elucidate the distinct contributions of maternal, placental, and fetal 5-HT sources across developmental time points.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"325-336"},"PeriodicalIF":2.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145126415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ontogeny of Catechol-O-Methyltransferase Expression in the Rat Prefrontal Cortex: Effects of Methamphetamine Exposure.","authors":"Lauren K Carrica, Joshua M Gulley","doi":"10.1159/000546689","DOIUrl":"10.1159/000546689","url":null,"abstract":"<p><strong>Introduction: </strong>Repeated use of methamphetamine (METH) is known to dysregulate the dopaminergic system and induce long-lasting changes in behavior, which may be influenced by sex and age of exposure. Catechol-o-methyltransferase (COMT) is an enzyme that is involved in the breakdown of catecholamines, and its role in dopamine clearance is thought to be especially important in the prefrontal cortex (PFC) where dopamine transporter expression is relatively scarce.</p><p><strong>Methods: </strong>The first study in this report utilized a rat model to characterize the ontogeny of COMT protein expression in the PFC and nucleus accumbens (NAc) across adolescence, which is a developmental stage that has been shown to involve significant reorganization of dopaminergic innervation. Drug-naïve male and female Sprague-Dawley rats were sacrificed on postnatal day (P) 29, 39, 49, or 69, and expression levels of COMT protein within the PFC and NAc were analyzed via Western blot. A separate group of rats were injected daily from P40 to P48 (adolescence) or P70 to P78 (adulthood) with saline or 3.0 mg/kg METH and sacrificed on P49 or P79.</p><p><strong>Results: </strong>We found that COMT expression in the PFC increases across adolescence in a sex-dependent manner but does not significantly change in the NAc during this timeframe. While METH decreased COMT in adult rats of both sexes, METH increased COMT expression in the PFC of rats exposed in adolescence.</p><p><strong>Conclusion: </strong>The results of this work suggest that exposure to METH during adolescence uniquely effects dopamine clearance within the PFC, potentially contributing to differences in neurobiological outcomes from METH use.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"182-192"},"PeriodicalIF":2.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12354207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200745","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":"Pathogenesis of Preterm Intraventricular Haemorrhage.","authors":"Beth R Piscopo, Amy E Sutherland, Atul Malhotra, Beth J Allison, Suzanne L Miller","doi":"10.1159/000546607","DOIUrl":"10.1159/000546607","url":null,"abstract":"<p><strong>Background: </strong>Intraventricular haemorrhage (IVH) is the primary neuropathology in infants born very preterm. IVH describes bleeding into the ventricular space of the newborn brain, originating from the germinal matrix, termed germinal matrix haemorrhage. IVH is diagnosed at a rate of 1 in 5 infants born very preterm (less than 32 weeks' gestation), but the incidence increases with earlier gestation at birth. IVH is graded in severity (I to IV), and the neurological sequelae of IVH in infants born very preterm are significant, with more than 1 in 4 infants with any grade of IVH subsequently diagnosed with a moderate to severe neurodevelopmental deficit, increasing to more than half of infants diagnosed with severe IVH (grade III/IV).</p><p><strong>Summary: </strong>The high susceptibility to IVH in infants born at less than 32 weeks' arises in part to the presence of the germinal matrix. The germinal matrix is a transient brain region that produces neural stem and progenitor cells. The germinal matrix region is rich in angiogenic blood vessels that have a low density of pericyte and astrocyte coverage to provide structural stability, and it is a border zone for vascular endpoints that are highly fragile to haemodynamic instability. In addition to immaturity, antenatal complications may also adversely impact cerebrovascular development, pericyte and astrocyte coverage, and subsequently the structural integrity of the blood-brain barrier that might increase the risk for IVH.</p><p><strong>Key messages: </strong>Here, we will report the maturational profile of cerebrovascular development in the extremely preterm neonate, and implications for susceptibility to IVH, the complications that may contribute to the risk of haemorrhage, and neurodevelopmental deficits that primarily arise from IVH. We aimed to elucidate the cellular foundations of IVH to provide insight into neuroprotective targets.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"225-236"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypothermia treatment in Hypoxia-Inducible Factor-1α Knockout Mice with Hypoxia-Ischemia.","authors":"R Ann Sheldon, Xiangning Jiang, Fuxin Lu, Nicholas R Stewart, Donna M Ferriero","doi":"10.1159/000544949","DOIUrl":"10.1159/000544949","url":null,"abstract":"<p><strong>Introduction: </strong>Hypoxia-inducible factor-1α (HIF-1α) has a wide-ranging role in the cellular responses to hypoxia. We previously found that neuron-specific HIF-1α-deficient mice (HIF-KO) that underwent neonatal hypoxia-ischemia (HI) had increased brain injury suggesting its neuroprotective function. To investigate whether HIF-1α is also involved in the mechanisms of protection by hypothermia (HT), the standard of care for hypoxic-ischemic encephalopathy, we tested the effect of HT on HIF-KO and wild-type (WT) littermates after HI in postnatal day 9 mice.</p><p><strong>Methods: </strong>Cooling at 32°C began 1 h following HI and lasted for 3.5 h. Mice were perfused 5-7 days later for histological determination of injury severity. For Western blots, mice were killed 4 h or 24 h after HI with HT or HI with normothermia (NT) and ipsilateral cortices and hippocampi were evaluated for expression of HIF-1α, spectrin, ERK1/2, phosphorylated-ERK1/2 (p-ERK), and RNA-binding motif protein 3 (RBM3), one of the main cold-inducible mRNA-binding proteins.</p><p><strong>Results: </strong>Histological evaluation showed WT mice with HT had less injury than WT with NT, but HIF-KO mice showed no reduction of injury with HT. Regionally, the reduction of injury in WT with HT is greater in the hippocampus than in the cortex. Protein expression of HIF-1α was lower in HIF-KO cortex at 4 h with NT or HT and at 24 h with NT, but HIF-1α was higher in WT with NT at 24 h. Expression of spectrin 145/150 in WT cortex with HT was not different than sham at 4 h, indicating limitation of necrosis with HT. In the HIF-KO cortex at 4 h spectrin 145/150 was higher in both NT and HT, indicating no protection with HT. In the hippocampus at 4 h and 24 h, spectrin 145/150 was elevated in all groups compared to sham. ERK activity, as represented by the ratio of p-ERK/ERK, was upregulated at 24 h in the cortex in WT with NT or HT compared to sham and in HIF-KO mice with NT or HT treatment compared to sham. RBM3 was elevated at 4 h in both WT and HIF-KO cortex with HT, but there was no change in the hippocampus.</p><p><strong>Conclusion: </strong>These results support a critical role for HIF-1α in the mechanisms of protection with HT.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"105-114"},"PeriodicalIF":2.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12353030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755738","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":"Costs of Underfunding Brain Development.","authors":"Masahiro Tsuji, Zoltán Molnár","doi":"10.1159/000546688","DOIUrl":"10.1159/000546688","url":null,"abstract":"<p><strong>Background: </strong>Healthcare costs are rising at an exponential rate. Given the constraints of limited resources, it is essential to make informed decisions about priorities to ensure the best possible health outcomes globally. The history of medicine illustrates how these priorities have shifted over time - from early focus on infectious diseases to later emphasis on noncommunicable conditions such as metabolic disorders. Today, neurodegenerative diseases and aging brain are the forefront of medical research, as these conditions profoundly affect individuals, families, and society.</p><p><strong>Summary: </strong>One in three people will experience a mental health disorder in their lifetime, yet it is not widely recognized that many of these conditions may have origins in pre-birth experiences and early life influences. Disruptions in progenitor proliferation, neuronal and glial migration, and differentiation during prenatal development can contribute to lifelong neurodevelopmental abnormalities. Despite the fundamental importance of brain development, most of the neuroscience funding is allocated to studying neurodegeneration, such as dementia and Parkinson's disease, while early life influences remain underexplored. Crucially, the impact of developmental factors begins even before conception. Environmental risks extend beyond direct maternal exposures during pregnancy; they include cumulative parental exposure to teratogenic agents affecting both male and female gametes, as well as early life environmental exposures affecting newborns, infants, and children. These influences are complex yet highly relevant to long-term health outcomes.</p><p><strong>Key messages: </strong>We urge greater recognition of the developmental origins of disease and advocate for increased investment in preventive strategies. These include lifestyle modifications, dietary improvements, targeted supplementation, regular exercise, and minimizing exposure to environmental pollutants. Addressing these factors proactively could yield profound benefits for both individual and public health.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"130-142"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}