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Autonomic nerve fibres in the tumour microenvironment regulate cancer initiation and dissemination, but how nerves emerge in tumours is currently unknown. Here we show that neural progenitors from the central nervous system that express doublecortin (DCX + ) infiltrate prostate tumours and metastases, in which they initiate neurogenesis. In mouse models of prostate cancer, oscillations of DCX + neural progenitors in the subventricular zone—a neurogenic area of the central nervous system—are associated with disruption of the blood–brain barrier, and with the egress of DCX + cells into the circulation. These cells then infiltrate and reside in the tumour, and can generate new adrenergic neurons. Selective genetic depletion of DCX + cells inhibits the early phases of tumour development in our mouse models of prostate cancer, whereas transplantation of DCX + neural progenitors promotes tumour growth and metastasis. In humans, the density of DCX + neural progenitors is strongly associated with the aggressiveness and recurrence of prostate adenocarcinoma. These results reveal a unique crosstalk between the central nervous system and prostate tumours, and indicate neural targets for the treatment of cancer. In a mouse model of prostate cancer, neural progenitors from the central nervous system that express doublecortin infiltrate tumours and metastases, and can generate new adrenergic neurons in tumours.

To determine if ventricular zone (VZ) and subventricular zone (SVZ) alterations are associated with intraventricular hemorrhage (IVH) and posthemorrhagic hydrocephalus, we compared postmortem frontal and subcortical brain samples from 12 infants with IVH and 3 nonneurological disease controls without hemorrhages or ventriculomegaly. Birth and expiration estimated gestational ages were 23.0-39.1 and 23.7-44.1 weeks, respectively; survival ranges were 0-42 days (median, 2.0 days). Routine histology and immunohistochemistry for neural stem cells (NSCs), neural progenitors (NPs), multiciliated ependymal cells (ECs), astrocytes (AS), and cell adhesion molecules were performed. Controls exhibited monociliated NSCs and multiciliated ECs lining the ventricles, abundant NPs in the SVZ, and medial vs. lateral wall differences with a complex mosaic organization in the latter. In IVH cases, normal VZ/SVZ areas were mixed with foci of NSC and EC loss, eruption of cells into the ventricle, cytoplasmic transposition of N-cadherin, subependymal rosettes, and periventricular heterotopia. Mature AS populated areas believed to be sites of VZ disruption. The cytopathology and extension of the VZ disruption correlated with developmental age but not with brain hemorrhage grade or location. These results corroborate similar findings in congenital hydrocephalus in animals and humans and indicate that VZ disruption occurs consistently in premature neonates with IVH.

Although schizophrenia is a brain disorder, increasing evidence suggests that there may be body-wide involvement in this illness. However, direct evidence of brain structures involved in the presumed peripheral-central interaction in schizophrenia is still unclear. Seventy-nine previously treatment-naïve first-episode schizophrenia patients who were within 2-week antipsychotics initial stabilization, and 41 age- and sex-matched healthy controls were enrolled in the study. Group differences in subcortical brain regional structures measured by MRI and the subclinical cardiovascular, metabolic, immune, and neuroendocrine biomarkers as indexed by allostatic load, and their associations were explored. Compared with controls, patients with schizophrenia had significantly higher allostatic load (P = .001). Lateral ventricle (P < .001), choroid plexus (P < .001), and thalamus volumes (P < .001) were significantly larger, whereas amygdala volume (P = .001) was significantly smaller in patients. The choroid plexus alone was significantly correlated with higher allostatic load after age, sex, education level, and the total intracranial volume were taken into account (t = 3.60, P < .001). Allostatic load was also significantly correlated with PANSS positive (r = 0.28, P = .016) and negative (r = −0.31, P = .008) symptoms, but in opposite directions. The peripheral multisystemic and central nervous system abnormalities in schizophrenia may interact through the choroid plexus during the early stage of the illness. The choroid plexus might provide a sensitive structural biomarker to study the treatment and prevention of brain-periphery interaction abnormalities in schizophrenia.

Long‐term sensorineural hearing loss (SNHL) is a prevalent condition associated with an increased risk of cognitive impairment. This study aimed to investigate the relationship among gradient connectivity, ventricle volumes, and transcriptional signatures in individuals experiencing cognitive deficits related to long‐term SNHL. This study enrolled 81 patients with long‐term SNHL and 78 healthy controls (HCs). All participants underwent audiological tests, neuropsychological assessment, and MRI scanning. Connectome gradient analysis and ventricular volume measurements were performed. Additionally, regional gene expression and neurotransmitter receptor data were integrated. Correlation analysis was conducted to examine associations between neuroimaging metrics and cognitive performance. Patients with SNHL had significantly higher hearing thresholds and worse cognitive performance than HCs. The principal gradient was compressed in the SNHL group, with significant differences in the default mode network and dorsal attention network. Enlarged volumes of the choroid plexus and lateral ventricles were also observed in the SNHL group. Correlation analysis revealed significant associations among ventricle volumes, gradient connectivity, and cognitive performance. Transcriptomic analysis revealed 496 genes associated with regions showing an increased principal gradient and 321 genes linked to regions with a decreased gradient. Enrichment analyses indicated these genes were implicated in synaptic plasticity, neurotransmitter regulation, energy metabolism, and neurodegenerative pathways. This study provides new insights into the multifaceted nature of SNHL‐related cognitive impairments, suggesting that gradient connectivity, ventricle volumes, and transcriptional signatures are interconnected and may serve as potential biomarkers for monitoring cognitive decline in individuals with long‐term SNHL. Future research should focus on elucidating the causal pathways and underlying biological mechanisms connecting these multimodal factors. Long‐term hearing loss with cognitive decline shows altered brain gradients, enlarged choroid plexus, and ventricles. These are linked to transcriptomic changes in synaptic, metabolic, and neurodegenerative pathways.

Background Diffuse astrocytoma (DA) is the most common intraparenchymal brain tumor, primarily occurring in the frontal and temporal lobes. However, its occurrence in the lateral ventricles is rare. Case presentation We report a rare case of a 57-year-old male with DA in the lateral ventricle. The patient presented with a one-day history of headache, nausea, and vomiting. Computed tomography (CT) revealed a round, low-density lesion in the right lateral ventricle. Magnetic resonance imaging (MRI) showed a T2-weighted/fluid-attenuated inversion recovery (T2/FLAIR) mismatch, low signal on diffusion-weighted imaging (DWI), reduced perfusion on arterial spin labeling (ASL), and no enhancement after gadolinium administration. Postoperatively, the patient's condition was initially stable but deteriorated rapidly on the third postoperative day, ultimately resulting in death several months later. Pathological evaluation revealed extensive microcyst formation, homogeneous tumor cell nuclei, and a tumor composed predominantly of moderately dense fibrous-type neoplastic cells within a microcystic matrix, with no mitosis, necrosis, or microvascular proliferation. Immunohistochemical analysis showed positive expression for GFAP, Olig-2, and IDH-1, with a Ki67 proliferation index of approximately 4%. The pathological diagnosis was diffuse astrocytoma (NOS). Conclusions This report details a rare case of headache caused by lateral ventricular diffuse astrocytoma characterized by typical T2/fluid-attenuated inversion recovery (FLAIR) mismatch signs. Despite the benign nature of lateral ventricle DA, surgical intervention necessitates manipulation of critical neural structures, including the corpus callosum and cortex, attributed to the tumor’s deep-seated location. Reducing postoperative complications and mortality remains a significant challenge.

Glioblastomas (GBMs) are highly aggressive, infiltrative, and heterogeneous brain tumors driven by complex genetic alterations. The basic-helix-loop-helix (bHLH) transcription factors ASCL1 and OLIG2 are dynamically co-expressed in GBMs; however, their combinatorial roles in regulating the plasticity and heterogeneity of GBM cells are unclear. Here, we show that induction of somatic mutations in subventricular zone (SVZ) progenitor cells leads to the dysregulation of ASCL1 and OLIG2, which then function redundantly and are required for brain tumor formation in a mouse model of GBM. Subsequently, the binding of ASCL1 and OLIG2 to each other’s loci and to downstream target genes then determines the cell types and degree of migration of tumor cells. Single-cell RNA sequencing (scRNA-seq) reveals that a high level of ASCL1 is key in specifying highly migratory neural stem cell (NSC)/astrocyte-like tumor cell types, which are marked by upregulation of ribosomal protein, oxidative phosphorylation, cancer metastasis, and therapeutic resistance genes. ASCL1 and OLIG2 are two basic-helix-loop-helix transcription factors that are highly co-expressed in glioblastoma (GBM). Here the authors find these two transcription factors function redundantly and are required for brain tumor initiation in a mouse model of GBM, while they possess inverse roles in determining tumor cell types and cell migration ability.

Galectin-3 (Gal-3) is an evolutionarily conserved and multifunctional protein that drives inflammation in disease. Gal-3’s role in the central nervous system has been less studied than in the immune system. However, recent studies show it exacerbates Alzheimer’s disease and is upregulated in a large variety of brain injuries, while loss of Gal-3 function can diminish symptoms of neurodegenerative diseases such as Alzheimer’s. Several novel molecular pathways for Gal-3 were recently uncovered. It is a natural ligand for TREM2 (triggering receptor expressed on myeloid cells), TLR4 (Toll-like receptor 4), and IR (insulin receptor). Gal-3 regulates a number of pathways including stimulation of bone morphogenetic protein (BMP) signaling and modulating Wnt signalling in a context-dependent manner. Gal-3 typically acts in pathology but is now known to affect subventricular zone (SVZ) neurogenesis and gliogenesis in the healthy brain. Despite its myriad interactors, Gal-3 has surprisingly specific and important functions in regulating SVZ neurogenesis in disease. Gal-1, a similar lectin often co-expressed with Gal-3, also has profound effects on brain pathology and adult neurogenesis. Remarkably, Gal-3’s carbohydrate recognition domain bears structural similarity to the SARS-CoV-2 virus spike protein necessary for cell entry. Gal-3 can be targeted pharmacologically and is a valid target for several diseases involving brain inflammation. The wealth of molecular pathways now known further suggest its modulation could be therapeutically useful.

Intraventricular tumors frequently provoke alterations in ventricular morphology. This study aims to quantificational assess perioperative dynamic fluctuations in the cerebrospinal fluid (CSF) volume within the lateral ventricles of patients harboring lateral ventricular tumors. A retrospective review encompassing 90 patients who underwent surgical intervention for lateral ventricular tumors at our institution was undertaken. Comprehensive observations at multiple perioperative time points were conducted, and LVCV analyses were performed to delineate the longitudinal dynamic alterations in ventricular morphology. Additionally, LVCV measurements were juxtaposed with data from 19 healthy subjects to stratify patients into two cohorts: those exhibiting preoperative increased LVCV and those without such changes. After surgical excision of intraventricular tumors, alterations in LVCV were compared between these cohorts, with a factor analysis undertaken specifically among patients demonstrating increased LVCV to elucidate potential influencing variables. 40 patients (44.4%) diagnosed with intraventricular tumors presenting with enlarged preoperative LVCV [74.6 (49.3–101.8) cm 3 ] compared with the normal subject group, and the LVCV demonstrated a significant postoperative [41.3 (27.6–67.5) cm 3 ] reduction in 3 months ( p  < 0.001). Meanwhile, 50 patients (55.6%) without LVCV enlargement [14.5 (8.1–21.0) cm 3 ] experienced a notable increase following surgery in 3 months [20.2 (14.1–33.3) cm 3 , p  = 0.002]. Preoperative increased LVCV is an important factor leading to the increased LVCV postoperatively ( p  = 0.022, OR = 26.239), however, compared to healthy subjects, both groups exhibited a trend toward normalization of LVCV value postoperatively ( p  = 0.165, p  = 0.072, respectively). Following appropriate surgical excision of the tumor, the preoperative increased LVCV associated with intraventricular tumors does not hinder the normalization trend of ventricular morphology. Not all ventricular dilation requires preventive long-term external ventricular drainage and aggressive ventriculoperitoneal shunt treatment.

The CreER/LoxP system is widely accepted to track neural lineages and study gene functions upon tamoxifen (TAM) administration. We have observed that prenatal TAM treatment caused high rates of delayed delivery and fetal mortality. This substance could produce undesired results, leading to data misinterpretation. Here, we report that administration of TAM during early stages of cortical neurogenesis promoted precocious neural differentiation, while it inhibited neural progenitor cell (NPC) proliferation. The TAM-induced inhibition of NPC proliferation led to deficits in cortical neurogenesis, dendritic morphogenesis, synaptic formation, and cortical patterning in neonatal and postnatal offspring. Mechanistically, by employing single-cell RNA-sequencing (scRNA-seq) analysis combined with in vivo and in vitro assays, we show TAM could exert these drastic effects mainly through dysregulating the Wnt-Dmrta2 signaling pathway. In adult mice, administration of TAM significantly attenuated NPC proliferation in both the subventricular zone and the dentate gyrus. This study revealed the cellular and molecular mechanisms for the adverse effects of TAM on corticogenesis, suggesting that care must be taken when using the TAM-induced CreER/LoxP system for neural lineage tracing and genetic manipulation studies in both embryonic and adult brains.