Secondary loss of miR-3607 reduced cortical progenitor amplification during rodent evolution

Expression of miR-3607 in embryonic mammalian cerebral cortex was lost in rodents, limiting progenitor cell proliferation.

Behavioral and Neuroanatomical Consequences of Cell-Type Specific Loss of Dopamine D2 Receptors in the Mouse Cerebral Cortex

Developmental dysregulation of dopamine D2 receptors (D2Rs) alters neuronal migration, differentiation, and behavior and contributes to the psychopathology of neurological and psychiatric disorders. The current study is aimed at identifying how cell-specific loss of D2Rs in the cerebral cortex may impact neurobehavioral and cellular development, in order to better understand the roles of this receptor in cortical circuit formation and brain disorders. We deleted D2R from developing cortical GABAergic interneurons (Nkx2.1-Cre) or from developing telencephalic glutamatergic neurons (Emx1-Cre). Conditional knockouts (cKO) from both lines, Drd2fl/fl, Nkx2.1-Cre+ (referred to as GABA-D2R-cKO mice) or Drd2fl/fl, Emx1-Cre+ (referred to as Glu-D2R-cKO mice), exhibited no differences in simple tests of anxiety-related or depression-related behaviors, or spatial or nonspatial working memory. Both GABA-D2R-cKO and Glu-D2R-cKO mice also had normal basal locomotor activity, but GABA-D2R-cKO mice expressed blunted locomotor responses to the psychotomimetic drug MK-801. GABA-D2R-cKO mice exhibited improved motor coordination on a rotarod whereas Glu-D2R-cKO mice were normal. GABA-D2R-cKO mice also exhibited spatial learning deficits without changes in reversal learning on a Barnes maze. At the cellular level, we observed an increase in PV+ cells in the frontal cortex of GABA-D2R-cKO mice and no noticeable changes in Glu-D2R-cKO mice. These data point toward unique and distinct roles for D2Rs within excitatory and inhibitory neurons in the regulation of behavior and interneuron development, and suggest that location-biased D2R pharmacology may be clinically advantageous to achieve higher efficacy and help avoid unwanted effects.

General Psychopathology, Cognition, and the Cerebral Cortex in 10-Year-Old Children: Insights From the Adolescent Brain Cognitive Development Study

General psychopathology and cognition are likely to have a bidirectional influence on each other. Yet, the relationship between brain structure, psychopathology, and cognition remains unclear. This brief report investigates the association between structural properties of the cerebral cortex [surface area, cortical thickness, intracortical myelination indexed by the T1w/T2w ratio, and neurite density assessed by restriction spectrum imaging (RSI)] with general psychopathology and cognition in a sample of children from the Adolescent Brain Cognitive Development (ABCD) study. Higher levels of psychopathology and lower levels of cognitive ability were associated with a smaller cortical surface area. Inter-regionally—across the cerebral cortex—the strength of association between an area and psychopathology is strongly correlated with the strength of association between an area and cognition. Taken together, structural deviations particularly observed in the cortical surface area influence both psychopathology and cognition.

Esquizencefalia bilateral gigante de labio abierto

Schizencephaly is a rare congenital brain malformation characterized by clefts in the cerebral cortex, it is classified in Type I (open lip) and Type II (close-lip). Patients with schizencephaly present seizures, hydrocephalus, motor and mental deficits. Ultrasound is used for in-utero and newborns patients’ diagnosis, and MRI or CT for already born patients. The management of schizencephaly is conservative, with rehabilitation in motor or mental deficits, medication or surgery for seizures and shunt in hydrocephalus with increased intracranial pressure. In the literature, only few giant bilateral cases have been reported. We report a case of giant bilateral open lip schizencephaly, in a 10-day old male patient, presenting with mild hypotonia and no seizures. This case is rare because the relatively benign features compared to other reported cases.

Localization of irritative zones in epilepsy with thermochromic silicone

Background: During epilepsy surgery, the gold standard to identify irritative zones (IZ) is electrocorticography (ECoG); however, new techniques are being developed to detect IZ in epilepsy surgery and in neurosurgery in general, such as infrared thermography mapping (ITM), and the use of thermosensitive/thermochromic materials. Methods: In a cohort study of consecutive patients with focal drug-resistant epilepsy of the temporal lobe treated with surgery, we evaluated possible adverse effects to the transient placement of a thermochromic/thermosensitive silicone (TTS) on the cerebral cortex and their postoperative evolution. Furthermore, we compared the precision of TTS for detecting cortical IZ against the gold standard ECoG and with ITM, as proof of concept. Results: We included 10 consecutive patients, 6 women (60%) and 4 men (40%). Age ranges from 15 to 56 years, mean 33.2 years. All were treated with unilateral temporal functional lobectomy. The mean hospital stay was 4 days. There were no immediate or late complications associated with the use of any of the modalities described. In the 10 patients, we obtained consistency in locating the IZ with ECoG, ITM, and the TTS. Conclusion: The TTS demonstrated biosecurity in this series. The accuracy of the TTS to locate IZ was similar to that of ECoG and ITM in this study. More extensive studies are required to determine its sensitivity and specificity.

Pumpkin seed oil and zinc attenuate chronic mild stress perturbations in the cerebral cortex of rats

Purpose This study aims to investigate the potential of pumpkin seed oil (PSO) and zinc to attenuate oxidative stress and neuroinflammation caused by chronic mild stress (CMS) in the cerebral cortex of male rats. Design/methodology/approach The rats were submitted to stress for six weeks and then the behavior of the rats was tested by forced swimming test (FST) and novel cage test. The treated groups were given venlafaxine (20 mg/kg), pumpkin seed oil (40 mg/kg) and zinc (4 mg/kg). The cortex homogenate was used for the detection of the oxidative stress parameters, the concentration of neurotransmitters, tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β), Na+/K+-ATPase activity, and the expression of histamine N-methyltransferase (Hnmt) and tyrosine hydroxylase (Th). Findings CMS causes a significant increase in immobility time in the FST and a significant decrease in the number of rearing in the novel cage test. CMS group showed a significant increase in alanine aminotransferase (ALT) activity, levels of cortisol, TNF-α, IL-1β, nitric oxide and malondialdehyde. CMS caused a significant decrease in the concentrations of serotonin, GABA, norepinephrine, and the activities of glutathione peroxidase, catalase, superoxide dismutase and Na+/K+-ATPase. CMS caused a marked reduction in the expression of Hnmt and Th in the cortex. PSO and zinc attenuated the Na+/K+-ATPase activity, oxidative parameters and neuroinflammation induced by the CMS, and this was reflected by the elevation of the concentration of neurotransmitters and reduction of cortisol and ALT, in addition to the behavior normalization. PSO and zinc attenuated the CMS by improving the antioxidant milieu and anti-inflammatory status of the cerebral cortex. Originality/value There are no studies on the effect of pumpkin seed oil on depression

A theory of cortical map formation in the visual brain

The cerebral cortex receives multiple afferents from the thalamus that segregate by stimulus modality forming cortical maps for each sense. In vision, the primary visual cortex also maps the multiple dimensions of the stimulus in patterns that vary across species for reasons unknown. Here we introduce a general theory of cortical map formation, which proposes that map diversity emerges from variations in sampling density of sensory space across species. In the theory, increasing afferent sampling density enlarges the cortical domains representing the same visual point allowing the segregation of afferents and cortical targets by additional stimulus dimensions. We illustrate the theory with a computational model that accurately replicates the maps of different species through afferent segregation followed by thalamocortical convergence pruned by visual experience. Because thalamocortical pathways use similar mechanisms for axon sorting and pruning, the theory may extend to other sensory areas of the mammalian brain.

The Role of Structure MRI in Diagnosing Autism

This study proposes a Computer-Aided Diagnostic (CAD) system to diagnose subjects with autism spectrum disorder (ASD). The CAD system identifies morphological anomalies within the brain regions of ASD subjects. Cortical features are scored according to their contribution in diagnosing a subject to be ASD or typically developed (TD) based on a trained machine-learning (ML) model. This approach opens the hope for developing a new CAD system for early personalized diagnosis of ASD. We propose a framework to extract the cerebral cortex from structural MRI as well as identifying the altered areas in the cerebral cortex. This framework consists of the following five main steps: (i) extraction of cerebral cortex from structural MRI; (ii) cortical parcellation to a standard atlas; (iii) identifying ASD associated cortical markers; (iv) adjusting feature values according to sex and age; (v) building tailored neuro-atlases to identify ASD; and (vi) artificial neural networks (NN) are trained to classify ASD. The system is tested on the Autism Brain Imaging Data Exchange (ABIDE I) sites achieving an average balanced accuracy score of 97±2%. This paper demonstrates the ability to develop an objective CAD system using structure MRI and tailored neuro-atlases describing specific developmental patterns of the brain in autism.

Compartmentalization and Interaction of Pax5 and Pax6 in Brain of Mice

Many transcription factors play important roles to maintain the microenvironment, integrity of the blood-brain barrier, the neurons-glia interaction, activities of microglia, composition of cerebrospinal fluid, metabolic activities, concentration of neurotransmitters, presence of inflammatory and anti-inflammatory cytokines, ischemia, stress, aging, neurological disorders, and diseases. The Paired box transcription factors and multifunctional proteins, Pax6 and Pax5 are expressed in brain. They regulate several regulators from cell cycle to cell death. The Pax5, a B-cell lineage-specific activator protein (BSAP), is expressed in the cerebellum, cerebral cortex, hippocampus, olfactory bulb, third ventricles, and choroid plexus. The Pax5 has been observed down-regulated in autism, mental retardation, and Glioblastoma multiforme. The Pax6 affects genes of neurodegeneration, immunological surveillance, and energy homeostasis in brain of mice. The Pax5 and Pax6 recognize several similar DNA sequences and regulate the expression of genes in a tissue-specific manner. Therefore, it is presumed that Pax5 and Pax6, are compartmentalized in brain of mice. Results indicate interactions, cell and tissue-specific compartmentalization, and co-localization of Pax5 and Pax6 in the cerebral cortex, cerebellum, and hippocampus in brain of mice.

Regulation of gene expression by the APP family in the adult cerebral cortex

Amyloid precursor protein (APP) is associated with both familial and sporadic forms of Alzheimer’s disease. APP has two homologs, amyloid precursor-like protein 1 and 2 (APLP1 and APLP2), and they have functional redundancy. APP intracellular c-terminal domain (AICD), produced by sequential α- or β- and γ-secretase cleavages, is thought to control gene expression, similarly as the ICD of Notch. To investigate the role of APP family in transcriptional regulation, we examined gene expression changes in the cerebral cortex of APP/APLP1/APLP2 conditional triple knockout (cTKO) mice, in which APP family members are selectively inactivated in excitatory neurons of the postnatal forebrain. Of the 12 previously reported AICD target genes, only Nep and Npas4 mRNA levels were significantly reduced in the cerebral cortex of cTKO mice, compared to littermate controls. We further examined global transcriptional changes by RNA-seq and identified 189 and 274 differentially expressed genes in the neocortex and hippocampus, respectively, of cTKO mice relative to controls. Gene Ontology analysis indicated that these genes are involved in a variety of cellular functions, including extracellular organization, learning and memory, and ion channels. Thus, inactivation of APP family alters transcriptional profiles of the cerebral cortex and affects wide-ranging molecular pathways.