Lateral expansion of the mammalian cerebral cortex is related to anchorage of centrosomes in apical neural progenitors.

The centrosome is the main microtubule organizing center in stem cells, and its mother centriole, anchored to the cell membrane, serves as the basal body of the primary cilium. Prolonged anchorage of centrosomes and primary cilia to the apical segment of the membrane of apical neural progenitor cells is considered vital for interkinetic nuclear translocation and repetitive cycling in the ventricular zone. In contrast, the basolateral anchorage of primary cilia has been regarded as the first step in delamination and conversion of apical to basal neural progenitor cells or neurons. Using electron microscopy analysis of serial sections, we show that centrosomes, in a fraction of cells, anchor to the basolateral cell membrane immediately after cell division and before development of cilia. In other cells, centrosomes situate freely in the cytoplasm, increasing their probability of subsequent apical anchorage. In mice, anchored centrosomes in the cells shortly after mitosis predominate during the entire cerebral neurogenesis, whereas in macaque monkeys, cytoplasmic centrosomes are more numerous. Species-specific differences in the ratio of anchored and free cytoplasmic centrosomes appear to be related to prolonged neurogenesis in the ventricular zone that is essential for lateral expansion of the cerebral cortex in primates.

Astrocyte diversity in the ferret cerebrum revealed with astrocyte-specific genetic manipulation.

Astrocytes in the cerebrum play important roles such as the regulation of synaptic functions, homeostasis, water transport, and the blood-brain barrier. It has been proposed that astrocytes in the cerebrum acquired diversity and developed functionally during evolution. Here, we show that like human astrocytes, ferret astrocytes in the cerebrum exhibit various morphological subtypes which mice do not have. We found that layer 1 of the ferret cerebrum contained not only protoplasmic astrocytes but also pial interlaminar astrocytes and subpial interlaminar astrocytes. Morphologically polarized astrocytes, which have a long unbranched process, were found in layer 6. Like human white matter, ferret white matter exhibited four subtypes of astrocytes. Furthermore, our quantification showed that ferret astrocytes had a larger territory size and a longer radius length than mouse astrocytes. Thus, our results indicate that, similar to the human cerebrum, the ferret cerebrum has a well-developed diversity of astrocytes. Ferrets should be useful for investigating the molecular and cellular mechanisms leading to astrocyte diversity, the functions of each astrocyte subtype and the involvement of different astrocyte subtypes in various neurological diseases.

The role of the primary sensorimotor system in generalized epilepsy: Evidence from the cerebello-cerebral functional integration.

The interaction between cerebellum and cerebrum participates widely in function from motor processing to high-level cognitive and affective processing. Because of the motor symptom, idiopathic generalized epilepsy (IGE) patients with generalized tonic-clonic seizure have been recognized to associate with motor abnormalities, but the functional interaction in the cerebello-cerebral circuit is still poorly understood. Resting-state functional magnetic resonance imaging data were collected for 101 IGE patients and 106 healthy controls. The voxel-based functional connectivity (FC) between cerebral cortex and the cerebellum was contacted. The functional gradient and independent components analysis were applied to evaluate cerebello-cerebral functional integration on the voxel-based FC. Cerebellar motor components were further linked to cerebellar gradient. Results revealed cerebellar motor functional modules were closely related to cerebral motor components. The altered mapping of cerebral motor components to cerebellum was observed in motor module in patients with IGE. In addition, patients also showed compression in cerebello-cerebral functional gradient between motor and cognition modules. Interestingly, the contribution of the motor components to the gradient was unbalanced between bilateral primary sensorimotor components in patients: the increase was observed in cerebellar cognitive module for the dominant hemisphere primary sensorimotor, but the decrease was found in the cerebellar cognitive module for the nondominant hemisphere primary sensorimotor. The present findings suggest that the cerebral primary motor system affects the hierarchical architecture of cerebellum, and substantially contributes to the functional integration evidence to understand the motor functional abnormality in IGE patients.

A novel preparation for histological analyses of intraventricular macrophages in the embryonic brain.

Microglia colonize the brain starting on embryonic day (E) 9.5 in mice, and their population increases with development. We have previously demonstrated that some microglia are derived from intraventricular macrophages, which frequently infiltrate the pallium at E12.5. To address how the infiltration of intraventricular macrophages is spatiotemporally regulated, histological analyses detecting how these cells associate with the surrounding cells at the site of infiltration into the pallial surface are essential. Using two-photon microscopy-based in vivo imaging, we demonstrated that most intraventricular macrophages adhere to the ventricular surface. This is a useful tool for imaging intraventricular macrophages maintaining their original position, but this method cannot be used for observing deeper brain regions. Meanwhile, we found that conventional cryosection-based and naked pallial slice-based observation resulted in unexpected detachment from the ventricular surface of intraventricular macrophages and their mislocation, suggesting that previous histological analyses might have failed to determine their physiological number and location in the ventricular space. To address this, we sought to establish a methodological preparation that enables us to delineate the structure and cellular interactions when intraventricular macrophages infiltrate the pallium. Here, we report that brain slices pretreated with agarose-embedding maintained adequate density and proper positioning of intraventricular macrophages on the ventricular surface. This method also enabled us to perform the immunostaining. We believe that this is helpful for conducting histological analyses to elucidate the mechanisms underlying intraventricular macrophage infiltration into the pallium and their cellular properties, leading to further understanding of the process of microglial colonization into the developing brain.

Therapeutic Effects of Metformin on Central Nervous System Diseases: A Focus on Protection of Neurovascular Unit.

Metformin is one of the most commonly used oral hypoglycemic drugs in clinical practice, with unique roles in neurodegeneration and vascular lesions. Neurodegeneration and vasculopathy coexist in many diseases and typically affect the neurovascular unit (NVU), a minimal structural and functional unit in the central nervous system. Its components interact with one another and are indispensable for maintaining tissue homeostasis. This review focuses on retinal (diabetic retinopathy, retinitis pigmentosa) and cerebral (ischemic stroke, Alzheimer's disease) diseases to explore the effects of metformin on the NVU. Metformin has a preliminarily confirmed therapeutic effect on the retinal NUV, affecting many of its components, such as photoreceptors (cones and rods), microglia, ganglion, Müller, and vascular endothelial cells. Since it rapidly penetrates the blood-brain barrier (BBB) and accumulates in the brain, metformin also has an extensively studied neuronal protective effect in neuronal diseases. Its mechanism affects various NVU components, including pericytes, astrocytes, microglia, and vascular endothelial cells, mainly serving to protect the BBB. Regulating the inflammatory response in NVU (especially neurons and microglia) may be the main mechanism of metformin in improving central nervous system related diseases. Metformin may be a potential drug for treating diseases associated with NVU deterioration, however, more trials are needed to validate its timing, duration, dose, clinical effects, and side effects.

Protective effects of Urtica dioica on the cerebral cortex damage induced by Potassium bromate in adult male albino rats.

Potassium bromate is used in cheese production, beer making and is also used in pharmaceutical and cosmetic. It is a proven carcinogen as it is a strong oxidizing agent that generates free radicals during xenobiotic metabolism. Urtica dioica (Ud) (from the plants' family of Urticaceae) is a plant that has long been used as a medicinal plant in many parts of the world. It has been shown to have anti-inflammatory, antioxidant and immunosuppressive properties. So, this study aimed to clarify the effect of Potassium bromate on the histological structure of cerebral cortex of adult male albino rats, evaluate the possible protective role of Urtica dioica. Thirty adult healthy male albino rats were divided into three groups; group I (Control group), group II (KBrO3 treated group). Group III (KBrO3 and Urtica dioica treated group).At the end of the experiment, rats in all groups were anesthetized and specimens were processed for light and electron microscope. Morphometric and statistical analyses were also performed. Nerve cells of the treated group showed irregular contours, dark nuclei, irregular nuclear envelopes, dilated RER cisternae, and mitochondria with ruptured cristae. Vacuolated neuropil was also observed. Immunohistochemically, stained sections for GFAP showed strong positive reaction in the processes of astrocytes. Recovery group showed revealed nearly the same as the histological picture as the control group. In conclusion, potassium bromate induces degenerative effects on neurons of cerebral cortex and urtica dioica provide an important neuroprotective effects against these damaging impacts through their antioxidant properties.

The Abundant Distribution and Duplication of SARS-CoV-2 in the Cerebrum and Lungs Promote a High Mortality Rate in Transgenic hACE2-C57 Mice.

Patients with COVID-19 have been reported to experience neurological complications, although the main cause of death in these patients was determined to be lung damage. Notably, SARS-CoV-2-induced pathological injuries in brains with a viral presence were also found in all fatal animal cases. Thus, an appropriate animal model that mimics severe infections in the lungs and brain needs to be developed. In this paper, we compared SARS-CoV-2 infection dynamics and pathological injuries between C57BL/6Smoc-Ace2em3(hACE2-flag-Wpre-pA)Smoc transgenic hACE2-C57 mice and Syrian hamsters. Importantly, the greatest viral distribution in mice occurred in the cerebral cortex neuron area, where pathological injuries and cell death were observed. In contrast, in hamsters, viral replication and distribution occurred mainly in the lungs but not in the cerebrum, although obvious ACE2 expression was validated in the cerebrum. Consistent with the spread of the virus, significant increases in IL-1ß and IFN-γ were observed in the lungs of both animals. However, in hACE2-C57 mice, the cerebrum showed noticeable increases in IL-1ß but only mild increases in IFN-γ. Notably, our findings revealed that both the cerebrum and the lungs were prominent infection sites in hACE2 mice infected with SARS-CoV-2 with obvious pathological damage. Furthermore, hamsters exhibited severe interstitial pneumonia from 3 dpi to 5 dpi, followed by gradual recovery. Conversely, all the hACE2-C57 mice experienced severe pathological injuries in the cerebrum and lungs, leading to mortality before 5 dpi. According to these results, transgenic hACE2-C57 mice may be valuable for studying SARS-CoV-2 pathogenesis and clearance in the cerebrum. Additionally, a hamster model could serve as a crucial resource for exploring the mechanisms of recovery from infection at different dosage levels.

[Qualitative and quantitative characteristics of structures of cerebral cortex structure in young people under conditions of chronic alcohol intoxication]. / Kachestvennaya i kolichestvennaya kharakteristika struktur kory golovnogo mozga u lits molodogo vozrasta v usloviyakh khronicheskoi alkogol'noi intoksikatsii.

OBJECTIVE: To study morphological changes of cerebral cortex in young people under the conditions of chronic alcohol intoxication (CAI). MATERIAL AND METHODS: Morphometric examination of cerebral cortex fragments obtained from 28 persons who died with a CAI diagnosis (average age was 38 years), and 25 subjects who died from other causes, which are not associated with alcohol consumption (average age was 39 years), was carried out. RESULTS: It was shown that neurons of pathological shapes, including hypo- and hyperchromic, pyknotic and «shadow-like¼, were dominant in group of CAI. There was an increase in the glial index and a greater intensity of perivascular and pericellular edema compared to the control group. CONCLUSION: Morphological changes of cerebral cortex under the conditions of CAI are non-specific and largely similar to neurodegenerative alterations in other pathological conditions, senile dementia. Clearer histological criteria for alcoholic encephalopathy are needed, including with the use of immunohistochemical methods.

Exposure to copper activates mitophagy and endoplasmic reticulum stress-mediated apoptosis in chicken (Gallus gallus) cerebrum.

A large amount of copper (Cu) used in production activities can lead to the enrichment of Cu in the environment, which can cause toxicity to animals. However, the toxicity mechanism of Cu on the cerebrum is still uncertain. Hence, a total of 240 chickens were separated into four groups in this study to reveal the potential connection between mitophagy and endoplasmic reticulum (ER) stress-mediated apoptosis in the chicken cerebrum in the case of excess Cu exposure. The cu exposure situation was simulated by diets containing various levels of copper (11 mg/kg, control group; 110 mg/kg, group I; 220 mg/kg, group II and 330 mg/kg, group III) for 49 days. The results of histology showed that vacuolar degeneration was observed in the treated groups, and the mitochondria swell and autophagosomes formation were found under excess Cu treatment. Additionally, the expression of mitophagy (PINK1, Parkin, LC3I, LC3II and p62) and ER stress (GRP78, PERK, ATF6, IRE1α, XBP1, CHOP, and JNK) indexes were significantly upregulated under excess Cu exposure. Furthermore, the mRNA and protein expression of Bcl-2 were decreased, while Bak1, Bax, Caspase12, and Caspase3 were increased compared to the control group. In summary, this study demonstrated that an overdose of Cu could induce mitophagy and ER stress-mediated apoptosis in the chicken cerebrum. These findings revealed an important potential connection between Cu toxicity and cerebrum damage, which provided a new insight into Cu neurotoxicity.

Fluid metabolic pathways after subarachnoid hemorrhage.

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating cerebrovascular disease with high mortality and morbidity. In recent years, a large number of studies have focused on the mechanism of early brain injury (EBI) and delayed cerebral ischemia (DCI), including vasospasm, neurotoxicity of hematoma and neuroinflammatory storm, after aSAH. Despite considerable efforts, no novel drugs have significantly improved the prognosis of patients in phase III clinical trials, indicating the need to further re-examine the multifactorial pathophysiological process that occurs after aSAH. The complex pathogenesis is reflected by the destruction of the dynamic balance of the energy metabolism in the nervous system after aSAH, which prevents the maintenance of normal neural function. This review focuses on the fluid metabolic pathways of the central nervous system (CNS), starting with ruptured aneurysms, and discusses the dysfunction of blood circulation, cerebrospinal fluid (CSF) circulation and the glymphatic system during disease progression. It also proposes a hypothesis on the metabolic disorder mechanism and potential therapeutic targets for aSAH patients. Cover Image for this issue: https://doi.org/10.1111/jnc.15384.

Mapping of whole-cerebrum resting-state networks using ultra-high resolution acquisition protocols.

Resting-state functional magnetic resonance imaging (fMRI) has been used in numerous studies to map networks in the brain that employ spatially disparate regions. However, attempts to map networks with high spatial resolution have been hampered by conflicting technical demands and associated problems. Results from recent fMRI studies have shown that spatial resolution remains around 0.7 × 0.7 × 0.7 mm3 , with only partial brain coverage. Therefore, this work aims to present a novel fMRI technique that was developed based on echo-planar-imaging with keyhole (EPIK) combined with repetition-time-external (TR-external) EPI phase correction. Each technique has been previously shown to be effective in enhancing the spatial resolution of fMRI, and in this work, the combination of the two techniques into TR-external EPIK provided a nominal spatial resolution of 0.51 × 0.51 × 1.00 mm3 (0.26 mm3 voxel) with whole-cerebrum coverage. Here, the feasibility of using half-millimetre in-plane TR-external EPIK for resting-state fMRI was validated using 13 healthy subjects and the corresponding reproducible mapping of resting-state networks was demonstrated. Furthermore, TR-external EPIK enabled the identification of various resting-state networks distributed throughout the brain from a single fMRI session, with mapping fidelity onto the grey matter at 7T. The high-resolution functional image further revealed mesoscale anatomical structures, such as small cerebral vessels and the internal granular layer of the cortex within the postcentral gyrus.

Pharmacokinetics and tissue distribution of orally administrated imidazole dipeptides in carnosine synthase gene knockout mice.

Imidazole dipeptides (ID) are abundant in skeletal muscle and the brain and have various functions, such as antioxidant, pH-buffering, metal-ion chelation. However, the physiological significance of ID has not been fully elucidated. In this study, we orally administered ID to conventional carnosine synthase gene-deficient mice (Carns-KO mice) to investigate the pharmacokinetics. Carnosine or anserine was administered at a dose of 500 mg (∼2 mmol) per kilogram of mouse body weight, and ID contents in the tissues were measured. No ID were detected in untreated Carns-KO mice. In the ID treatment groups, the ID concentrations in the tissues increased in a time-dependent manner in the gastrocnemius muscle, soleus muscle, and cerebrum after ID administration. Our findings suggest that the Carns-KO mice are a valuable animal model for directly evaluating the effects of dietary ID and for elucidating the physiological functions of oral ID administration.

Deltamethrin induces apoptosis in cerebrum neurons of quail via promoting endoplasmic reticulum stress and mitochondrial dysfunction.

Deltamethrin (DLM) is a widely used and highly effective insecticide. DLM exposure is harmful to animal and human. Quail, as a bird model, has been widely used in the field of toxicology. However, there is little information available in the literature about quail cerebrum damage caused by DLM. Here, we investigated the effect of DLM on quail cerebrum neurons. Four groups of healthy quails were assigned (10 quails in each group), respectively given 0, 15, 30, and 45 mg/kg DLM by gavage for 12 weeks. Through the measurements of quail cerebrum, it was found that DLM exposure induced obvious histological changes, oxidative stress, and neurons apoptosis. To further explore the possible molecular mechanisms, we performed real-time quantitative PCR to detect the expression of endoplasmic reticulum (ER) stress-related mRNA such as glucose regulated protein 78 kD, activating transcription factor 6, inositol requiring enzyme, and protein kinase RNA (PKR)-like ER kinase. In addition, we detected ATP content in quail cerebrum to evaluate the functional status of mitochondria. The study showed that DLM exposure significantly increased the expression of ER stress-related mRNA and decreased ATP content in quail cerebrum tissues. These results suggest that chronic exposure to DLM induces apoptosis of quail cerebrum neurons via promoting ER stress and mitochondrial dysfunction. Furthermore, our results provide a novel explanation for DLM-induced apoptosis of avian cerebrum neurons.

Hemispheric lateralization, endothelial function, and arterial compliance in chronic post-stroke individuals: A cross-sectional exploratory study.

Purpose/Aim: Cardiovascular function is controlled and regulated by a functional brain-heart axis. Although the exact mechanism is not fully understood, several studies suggest a hemispheric asymmetry in the neural control of cardiovascular function. Thus, the purpose of this study was to examine whether endothelial function and arterial compliance differ between individuals with left- and right-sided strokes.Materials and Methods: This was a cross-sectional exploratory study. Thirty individuals more than 6 months after stroke participated in the study. The endothelial function was assessed by ultrasound-measured flow-mediated dilation of the nonparetic arm brachial artery (baFMD). The arterial stiffness was assessed by measuring carotid-femoral pulse wave velocity (cfPWV) and central aortic pulse wave analysis [augmentation index (AIx), augmentation index normalized to a heart rate of 75 bpm (AIx@75) and reflection magnitude (RM)] using applanation tonometry. Results: Participants with right-sided stroke had worse endothelial function than those with left-sided stroke. This difference (baFMD = 2.51%) was significant (p = 0.037), and it represented a medium effect size (r = 0.38). Likewise, they had higher arterial stiffness than those with left-sided stroke. This difference (AIx = 10%; RM = 7%) was significant (p = 0.011; p = 0.012), and it represented a medium effect size (r = 0.48; r = 0.47).Conclusions: Our findings suggest that individuals with right-sided stroke have reduced endothelial function and arterial compliance compared to those with left-sided stroke. These data may indicate that those with right-sided strokes are more susceptible to cardiovascular events.

[Neurocovid-19: effects of COVID-19 on the brainNeurocovid-19: efeitos da COVID-19 no cérebro]. / Neurocovid-19: efectos del COVID-19 en el cerebro.

In the COVID-19 pandemic, direct and indirect effects on mental health have been reported, including neurological, neuropsychiatric, and neuropsychological symptoms with possible long-term effects. Also, it is suspected that in the coming years there could be a worldwide increase in the incidence of neurodegenerative disorders.The objective of this article is to review the most up-to-date information on brain damage associated with COVID-19, as well as the neuropsychiatric symptoms of the disease. The exact mechanisms of brain damage have not yet been clarified, and further longitudinal and international research-including studies that incorporate epidemiological, clinical, and diagnostic variables-is required to define these mechanisms and establish their impact on mental health, as well as their long-term consequences.

Durante a pandemia de COVID-19 foram relatados efeitos diretos e indiretos na saúde mental, incluindo sintomas neurológicos, neuropsiquiátricos e neuropsicológicos com possíveis efeitos no longo prazo, e suspeita-se que nos próximos anos poderá haver um aumento nas taxas de incidência de doenças neurodegenerativas em todo o mundo.O objetivo deste artigo é revisar as informações mais atualizadas sobre os danos cerebrais associados à COVID-19 e seus sintomas neuropsiquiátricos. Os mecanismos exatos desses danos ainda não foram esclarecidos, sendo necessário continuar com pesquisas longitudinais e internacionais ­ incluindo estudos que contenham variáveis ­ epidemiológicas, clínicas e diagnósticas ­ para defini-los e estabelecer sua repercussão na saúde mental, bem como suas consequências no longo prazo.

LIF-IGF Axis Contributes to the Proliferation of Neural Progenitor Cells in Developing Rat Cerebrum.

In rodent models, leukemia inhibitory factor (LIF) is involved in cerebral development via the placenta, and maternal immune activation is linked to psychiatric disorders in the child. However, whether LIF acts directly on neural progenitor cells (NPCs) remains unclear. This study performed DNA microarray analysis and quantitative RT-PCR on the fetal cerebrum after maternal intraperitoneal or fetal intracerebral ventricular injection of LIF at day 14.5 (E14.5) and determined that the expression of insulin-like growth factors (IGF)-1 and -2 was induced by LIF. Physiological IGF-1 and IGF-2 levels in fetal cerebrospinal fluid (CSF) increased from E15.5 to E17.5, following the physiological surge of LIF levels in CSF at E15.5. Immunostaining showed that IGF-1 was expressed in the cerebrum at E15.5 to E19.5 and IGF-2 at E15.5 to E17.5 and that IGF-1 receptor and insulin receptor were co-expressed in NPCs. Further, LIF treatment enhanced cultured NPC proliferation, which was reduced by picropodophyllin, an IGF-1 receptor inhibitor, even under LIF supplementation. Our findings suggest that IGF expression and release from the NPCs of the fetal cerebrum in fetal CSF is induced by LIF, thus supporting the involvement of the LIF-IGF axis in cerebral cortical development in an autocrine/paracrine manner.

Metabolism of [1,6-13 C]glucose in the cerebellum of 18-day-old rats: Comparison with cerebral metabolism.

There is little information on metabolism in developing cerebellum despite the known importance of this region in cognition and motor tasks. Ex vivo 1 H- and 13 C-NMR spectroscopy were used to determine metabolism during late postnatal development in cerebellum and cerebrum from 18-day-old rat pups after intraperitoneal (i.p.) injection of [1,6-13 C]glucose. The concentration of several metabolites in cerebellum was distinctly different than cerebrum; alanine, glutamine, creatine and myo-inositol were higher in cerebellum than cerebrum, the concentrations of lactate, GABA, aspartate and N-acetylaspartate (NAA) were lower in cerebellum than in cerebrum, and levels of glutamate, succinate, choline and taurine were similar in both brain regions. The incorporation of label from the metabolism of [1,6-13 C]glucose into most isotopomers of glutamate (GLU), glutamine (GLN), GABA and aspartate was lower in cerebellum than in cerebrum. Incorporation of label into the C2 position of lactate via the pyruvate recycling pathway was found in both brain regions. The ratio of newly synthesized GLN/GLU was significantly higher in cerebellum than in cerebrum indicating relatively active metabolism via glutamine synthetase in cerebellar astrocytes at postnatal day 18. This is the first study to determine metabolism in the cerebellum and cerebrum of male and female rat brain.

Pyramid-Shape Crossings and Intercrossing Fibers Are Key Elements for Construction of the Neural Network in the Superficial White Matter of the Human Cerebrum.

Structural analysis of the superficial white matter is prerequisite for the understanding of highly integrated functions of the human cerebral cortex. However, the principal components, U-fibers, have been regarded as simple wires to connect adjacent gyri (inter-gyral U-fibers) but have never been thought as indispensable elements of anatomical structures to construct the cortical network. Here, we reported such novel structures made of U-fibers. Seven human cerebral hemispheres were treated with Klingler's method and subjected to fiber dissection (FD). Additionally, tractography using diffusion spectrum imaging (DSI) was performed. Our FD and DSI tractography succeeded disclosing a new type of U-fibers that was hidden in and ran along the white matter ridge of a gyral convolution (intra-gyral U-fibers). They were distinct from inter-gyral U-fibers which paved sulcal floors. Both intra- and inter-gyral U-fibers converged from various directions into junctional areas of white matter ridges, organizing novel anatomical structures, "pyramid-shape crossings". U-fibers to form pyramid-shape crossings also render routes for communication between crossings. There were 97 (mean, range 73-148) pyramid-shape crossings per lateral cortical surface. They are key structures to construct the neural network for intricate communications throughout the entire cerebrum. They can be new anatomical landmarks, too, for the segmentation of the cerebral cortex.

Cadmium exposure promotes activation of cerebrum and cerebellum ferroptosis and necrosis in swine.

Cadmium(Cd) is a toxic and carcinogenic heavy metal pollutant leading to serious damage in various organs. Ferroptosis and necrosis as inflammation-related cell death are involved in several diseases of nervous system. In the present study, 10 weaning piglets with similar weight for 6 weeks were randomly divided into two groups. The daily grain containing 0 mg and 20 mg/kg of Cd chloride was fed in 20-26 â„ƒ environment, animals were sacrificed to collect cerebrum and cerebellum tissues after 40 days. Morphology and ultrastructure results were observed using HE and TEM. Moreover, molecular biological technologies western blot and qRT-PCR were used to detect the expression abundance of genes. Cerebrum and cerebellum injury was observed in Cd-exposed group, antioxidant capacity decreased significantly and oxidative stress increased; immunofluorescence, real-time quantification, and western blot results showed decreased necrosis genes and increased ferroptosis pathway genes abundance in cerebrum, whereas the results were reversed in cerebellum. These results indicated that Cd exposure can activated necrosis and ferroptosis pathways by increased oxidative stress, further resulting in cerebrum and cerebellum damage in pigs. These findings may provide a theoretical basis for early monitoring of Cd exposure in environment.

The genetic regulation of size variation in the transcriptome of the cerebrum in the chicken and its role in domestication and brain size evolution.

BACKGROUND: Large difference in cerebrum size exist between avian species and populations of the same species and is believed to reflect differences in processing power, i.e. in the speed and efficiency of processing information in this brain region. During domestication chickens developed a larger cerebrum compared to their wild progenitor, the Red jungle fowl. The underlying mechanisms that control cerebrum size and the extent to which genetic regulation is similar across brain regions is not well understood. In this study, we combine measurement of cerebrum size with genome-wide genetical genomics analysis to identify the genetic architecture of the cerebrum, as well as compare the regulation of gene expression in this brain region with gene expression in other regions of the brain (the hypothalamus) and somatic tissue (liver). RESULTS: We identify one candidate gene that putatively regulates cerebrum size (MTF2) as well as a large number of eQTL that regulate the transcriptome in cerebrum tissue, with the majority of these eQTL being trans-acting. The overall regulation of gene expression variation in the cerebrum was markedly different to the hypothalamus, with relatively few eQTL in common. In comparison, the cerebrum tissue shared more eQTL with a distant tissue (liver) than with a neighboring tissue (hypothalamus). CONCLUSION: The candidate gene for cerebrum size (MTF2) has previously been linked to brain development making it a good candidate for further investigation as a regulator of inter-population variation in cerebrum size. The lack of shared eQTL between the two brain regions implies that genetic regulation of gene expression appears to be relatively independent between the two brain regions and suggest that coevolution between these two brain regions might be more functionally driven than developmental. These findings have relevance for current brain size evolution theories.