Astrocytes are the largest glial population in the mammalian brain. However, we have a minimal understanding of astrocyte development, especially fate specification in different regions of the brain. Through lineage tracing of the progenitors of the third ventricle (3V) wall via in-utero electroporation in the embryonic mouse brain, we show the fate specification and migration pattern of astrocytes derived from radial glia along the 3V wall. Unexpectedly, radial glia located in different regions along the 3V wall of the diencephalon produce distinct cell types: radial glia in the upper region produce astrocytes and those in the lower region produce neurons in the diencephalon. With genetic fate mapping analysis, we reveal that the first population of astrocytes appears along the zona incerta in the diencephalon. Astrogenesis occurs at an early time point in the dorsal region relative to that in the ventral region of the developing diencephalon. With transcriptomic analysis of the region-specific 3V wall and lateral ventricle (LV) wall, we identified cohorts of differentially-expressed genes in the dorsal 3V wall compared to the ventral 3V wall and LV wall that may regulate astrogenesis in the dorsal diencephalon. Together, these results demonstrate that the generation of astrocytes shows a spatiotemporal pattern in the developing mouse diencephalon.
Mice ; Animals ; Astrocytes ; Neuroglia/physiology* ; Diencephalon ; Brain ; Neurons ; Mammals

Anti-Ma2-associated encephalitis is one of the paraneoplastic neurological syndromes. It has been shown to be associated with various neoplasms, mainly testicular, lung, and breast cancers. Most patients with anti-Ma2-associated encephalitis present limbic-diencephalic-brainstem dysfunctions such as seizure, mood disorder, excessive daytime sleepiness, and ophthalmoparesis. Some patients develop symptoms indicating the multifocal involvement of the limbic system, diencephalon, or brainstem. However, there are few case studies of anti-Ma2-associated encephalitis presenting as isolated hypersomnia. We report a case of anti-Ma2-associated encephalitis presenting as hypersomnia.
Brain Stem ; Breast ; Diencephalon ; Disorders of Excessive Somnolence* ; Encephalitis* ; Humans ; Limbic System ; Lung ; Mood Disorders ; Ophthalmoplegia ; Paraneoplastic Syndromes ; Seizures

The brain stem consists of medulla oblongta, pons and midbrain. It is sited in posterior cranial fossa. It contains numerous intrinsic neuron cell bodies and their processes, some of which are the brain stem homologues of spinal neuronal groups. These include the sites of termination and cells of origin of axons that enter or leave the brain stem through the cranial nerves. Cranial nerves provide sensory, motor and autonomic innervations of structures that are mostly in the head and neck. The reticular formation is an extensive network of neurons that extends throughout the length of brain stem and is continuous rostrally to diencephalon and caudally to its spinal counterpart. Clinically, damage to the brain stem is often devastating and life threatening. This is because it is a structurally and functionally compact region. Therefore, it is important to build basic knowledge about neuroanatomy of brain stem.
Axons ; Brain Stem* ; Cranial Fossa, Posterior ; Cranial Nerves ; Diencephalon ; Head ; Mesencephalon ; Neck ; Neuroanatomy* ; Neurons ; Pons ; Reticular Formation

BACKGROUND: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces an irreversible and severe parkinsonian-like syndrome. A licorice compound glycyrrhizin exerts a cytoprotective or anti-oxidant effect in various disease conditions, but its effect against the MPTP-induced brain tissue damage remains uncertain. The present study elucidates the protective effects of glycyrrhizin against brain tissue damage in the MPTP mouse model of Parkinson's disease. METHODS: We measured the activities of antioxidant enzymes and formation of tissue peroxidation products in the brains of MPTP-treated mice. We also performed an in vitro assay to examine the effects of 1-methyl-4-phenylpyridinium (MPP+) on the mitochondrial respiratory electron flow, membrane potential and cytochrome c release and measured the scavenging action of glycyrrhizin against reactive oxygen species. RESULTS: The MPTP treatment increased activities of total superoxide dismutase, catalase, and glutathione peroxidase and levels of malondialdehyde and carbonyls in the basal ganglia, diencephalon plus midbrain compared to the control mouse brain. Co-administration of glycyrrhizin (16.8 mg/kg = 20 micrometer) attenuated the MPTP effect on the enzyme activities and formation of tissue peroxidation products. Glycyrrhizin attenuated the 500 micrometer MPP+ -induced inhibition of electron flow, changes in the membrane potential and cytochrome c release in isolated brain mitochondria. Glycyrrhizin (1-50 micrometer) showed a scavenging action against superoxide radicals, hydrogen peroxide and hydroxyl radicals. CONCLUSIONS: Glycyrrhizin may prevent the toxicity of MPTP against brain tissue by suppressing mitochondrial damage and oxidative tissue damage. Glycyrrhizin seems to attenuate oxidative brain tissue damage occurring in Parkinson's disease through antioxidant action and prevention of mitochondrial dysfunction.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine* ; 1-Methyl-4-phenylpyridinium ; Animals ; Antioxidants ; Basal Ganglia ; Brain ; Catalase ; Cytochromes c ; Diencephalon ; Glutathione Peroxidase ; Glycyrrhiza ; Glycyrrhizic Acid* ; Hydrogen Peroxide ; Malondialdehyde ; Membrane Potentials ; Mesencephalon ; Mice* ; Mitochondria ; Parkinson Disease* ; Reactive Oxygen Species ; Superoxide Dismutase ; Superoxides

The Eph family is thought to exert its function through the complementary expression of receptors and ligands. The dorsal mesencephalon appears to be segmented into two broad regions demarcated by the mutually exclusive expression of EphA receptors and ephrinA ligands. In this study, we analyzed transgenic embryos expressing ephrinA2 in the anterior region of the developing midbrain where the EphA8 receptor is expressed. First, 1% of transgenic embryos showed cephalic neural tube closure defects. Second, it was confirmed that mis-expression of ephrin-A2 in the anterior mesencephalon induced an increase in the EphA8 tyrosine kinase activity. Accordingly, an increased MAPK activity was also detected in the anterior mesencephalon of E14.5 transgenic embryo. Third, cell adhesion assay revealed that mis-expression of ephrinA2 promoted cell attachment to fibronectin. Taken together, these findings suggest that co-expression of EphA receptors and ephrinA ligands significantly alter cell behaviors including cell adhesion.
Animals ; Cell Adhesion ; Diencephalon* ; Embryonic Structures ; Ephrin-A2 ; Fibronectins ; Humans ; Ligands ; Mesencephalon* ; Mice* ; Mice, Transgenic ; Neural Tube ; Protein-Tyrosine Kinases ; Receptor, EphA8 ; Receptors, Eph Family

Japanese encephalitis virus (JEV)may cause acute encephalitis in humans and induce severe cytopathic effects in various types of cultured cells. To investigate whether JEV infection induces apoptosis, we examined DNA fragmentation and apoptosis in the specific region of the JEV infected mouse brain by DNA oligonucleosomal laddering and in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)technique and immunohistochemical study. JEV infections in the mouse brain were detected in the telencephalon, the diencephalons, and the brain stem, but not in the cerebellum and the hippocampus. Fragmentation of cellular DNA into oligonucleosome-length ladders was only observed in tissue samples prepared from the cerebral cortex. In addition, the large number of TUNEL-positive cells was observed in the cerebral cortex. Double-labeling experiment with TUNEL staining and immunostaining for the JEV showed that TUNEL-positive neurons containing JEV immunoreactivity. These results suggest that JEV infection may evoke apoptotic neuronal death in the mouse brain, which plays an important role in the pathogenesis of Japanese encephalitis.
Animals ; Apoptosis ; Asian Continental Ancestry Group* ; Brain Stem ; Brain* ; Cells, Cultured ; Cerebellum ; Cerebral Cortex ; Diencephalon ; DNA ; DNA Fragmentation ; Encephalitis ; Encephalitis Virus, Japanese* ; Encephalitis, Japanese* ; Hippocampus ; Humans ; Immunohistochemistry ; In Situ Nick-End Labeling ; Mice* ; Neurons* ; Telencephalon

TrkA is essential components of the high-affinity NGF receptor necessary to mediate biological effects of the neurotrophins NGF. Here we report on the expression of trkA in the cerebral cortex and diencephalon of mongolian gerbils during postnatal development. The expression of trkA was identified by immunohistochemical method. In parietal cortex and piriform cortex, higher levels of trkA-IR (immunoreactivity) were detected at 3 days postnatal (P3) and at P9. Although trkA was not expressed till P3 in the parietal cortex, it was detectable at birth in the piriform cortex. Several regions, such as Layers I, IV & VI, did not show much expression. Layer I showed especially weak labeling. In the hippocampus, thalamus, and hypothalamus, higher levels of trkA-IR were detected at P6 and P12 than earlier days. But trkA was not expressed at birth in the hippocampus, at P3 in the reticular thalamic nucleus (Rt), or neonatally in the dorsomedial hypothalamic nucleus (DM). This data shows that expression of trkA is developmentally regulated and suggests that high affinity neurotrophin-receptors mediate a transient response to neurotrophines in the cerebral cortex and diencephalon during mongolian gerbil brain ontogeny.
Animals ; Animals, Newborn ; Cerebral Cortex/*metabolism ; Diencephalon/*metabolism ; Gerbillinae/*metabolism ; Immunohistochemistry/veterinary ; Nerve Growth Factor/metabolism ; Receptor, trkA/*metabolism

PURPOSE: To identify the brain centers associated with visually evoked sexual arousal in the human brain, and to investigate the neural mechanism for sexual arousal using functional MRI (fMRI). MATERIALS AND METHODS: A total of 20 sexually potent volunteers consisting of 10 males (mean age: 24) and 10 females (mean age: 23) underwent fMRI on a 1.5 T MR scanner (GE Signa Horizon). The fMRI data were obtained from 7 slices (10 mm slice thickness) parallel to the AC-PC (anterior commissure and posterior commissure) line, giving a total of 511 MR images. The sexual stimulation consisted of a 1-minute rest with black screen, followed by a 4-minute stimulation by an erotic video film, and concluded with a 2-minute rest. The brain activation maps and their quantification were analyzed by the statistical parametric mapping (SPM 99) program. RESULTS: The brain activation regions associated with visual sexual arousal in the limbic system are the posterior cingulate gyrus, parahippocampal gyrus, hypothalamus, medial cingulate gyrus, thalamus, amygdala, anterior cingulate gyrus, insula, hippocampus, caudate nucleus, globus pallidus and putamen. Especially, the parahippocampal gyrus, cingulate gyrus, thalamus and hypothalamus were highly activated in comparison with other areas. The overall activities of the limbic lobe, diencephalon, and basal ganglia were 11.8%, 10.5%, and 3.4%, respectively. In the correlation test between brain activity and sexual arousal, the hypothalamus and thalamus showed positive correlation, but the other brain areas showed no correlation. CONCLUSION: The fMRI is useful to quantitatively evaluate the cerebral activation associated with visually evoked, sexual arousal in the human brain. This result may be helpful by providing clinically valuable information on sexual disorder in humans as well as by increasing the understanding of the neuroanatomical correlates of sexual arousal.
Amygdala ; Arousal* ; Basal Ganglia ; Brain ; Caudate Nucleus ; Diencephalon ; Female ; Globus Pallidus ; Gyrus Cinguli ; Hippocampus ; Humans ; Hypothalamus ; Hypothalamus, Middle ; Limbic System* ; Magnetic Resonance Imaging* ; Male ; Parahippocampal Gyrus ; Putamen ; Thalamus ; Volunteers

Platelet-derived growth factor (PDGF) was initially described for its mitogenic activity on smooth muscle cells, fibroblast, and glial cells. The biological activities of PDGF include stimulation of mitogenesis, differentiation, wound healing, inflammation, and tumor formation. The localization of platelet-derived growth factor-alpha Receptor (PDGF-alpha R) in central nervous system was commonly restricted to oligodendrocyte progenitors during late embryonic and postnatal development. However, several studies recently demonstrated that postnatal neurons could also synthesize PDGF-alpha R in rodents. In the present study, to analyze the distributional pattern of PDGF-alpha R during postnatal development of the canine CNS, we used immunohistochemical method on sections of canine brain tissue. We found that neurons of various CNS regions, including cerebral cortex, striatum, diencephalon, nuclei of brain stem, cerebellum, spinal cord, exhibited the immunoreactivity to PDGF-alpha R as early as postnatal day 0. Generally PDGF-alpha R immunoreactivity was well localized in the dendrites and axons of neuron during the postnatal day 14 and postnatal day 28, and then showed diminished pattern. But neuronal immunoreactivity to PDGF-alpha R were maintained postnatal 6 month. These results suggest that the localization of PDGF-alpha R in postnatal developing neurons supports the several roles of PDGF for neurons including maturation and survival.
Axons ; Brain ; Brain Stem ; Central Nervous System ; Cerebellum ; Cerebral Cortex ; Dendrites ; Diencephalon ; Fibroblasts ; Immunohistochemistry ; Inflammation ; Myocytes, Smooth Muscle ; Neuroglia ; Neurons ; Oligodendroglia ; Platelet-Derived Growth Factor* ; Rodentia ; Spinal Cord ; Wound Healing

BACKGROUND AND OBJECTIVES: The transsynaptic transfer of neurotropic viruses is an effective tool for tracing chains of connected neurons, because replication of virus in the recipient neurons after the transfer amplifies the "tracer signal". The aim of this study is to identify the central neural pathways projecting to the facial nerve using the Bartha strain of the Pseudorabies virus (PRV-Ba )as a transsynaptic tracer. MATERIALS AND METHODS: PRV-Ba was injected into the facial nerve in the stylomastoid foramen of a rat, and was localized in the rat brain with light microscopic immunohistochemistry using primary antibodies against the PRV-Ba. Sequential tracing was carried out on the retrogradely labeled neurons were done. RESULTS: The shapes of upper motor neurons of facial nerve were mostly ovoid or polygonal. The positive immunoreactive cells observed in the brainstem nuclei included raphe obscurus nucleus, facial nucleus, parvocellular reticular nucleus, spinal trigeminal nucleus, ventral parabrachial nucleus, central gray, and dorsal raphe nucleus. Other positive cells stained in the diencephalon were found in periventricular hypothalamic nucleus, dorsal hypothalamic area, orbital gyri, and infralimbic cortex in the frontal lobe. CONCLUSIONS: These results show the central neural pathways of facial nerve using PRV-Ba.
Animals ; Antibodies ; Brain ; Brain Stem ; Diencephalon ; Facial Nerve ; Frontal Lobe ; Herpesvirus 1, Suid ; Immunohistochemistry ; Motor Neurons ; Neural Pathways* ; Neurons ; Orbit ; Raphe Nuclei ; Rats ; Trigeminal Nucleus, Spinal