Ontogeny of synaptophysin and synaptoporin in the central nervous system

The expression of the synaptic vesicle antigens synaptophysin (SY) and synaptoporin (SO) was studied in the rat striatum, which contains a nearly homogeneous population of GABAergic neurons. In situ hybridization revealed high levels of SY transcripts in the striatal anlage from embryonic day (E) 14 until birth. In contrast. SO hybridization signals were low, and no immunoreactive cell bodies were detected at these stages of development. At E 14, SY-immunoreactivity was restricted to perikarya. In later prenatal stages of development SY-immunoreactivity appeared in puncta (identified as terminals containing immunostained synaptic vesicles), fibers, thick fiber bundles and ‘patches’. In postnatal and adult animals, perikarya of striatal neurons exhibited immunoreaction for SO; ultrastructurally SO antigen was found in the Golgi apparatus and in multivesicular bodies. SO-positive boutons were rare in the striatum. In the neuropil, numerous presynaptic terminals positive for SY were observed. Our data indicate that the expression of synaptic vesicle proteins in GABAergic neurons of the striatum is developmentally regulated. Whereas SY is prevalent during embryonic development, SO is the major synaptic vesicle antigen expressed postnatally by striatal neurons which project to the globus pallidus and the substantia nigra. In contrast synapses of striatal afferents (predominantly from cortex, thalamus and substantia nigra) contain SY

Broad Epigenetic Signature of Maternal Care in the Brain of Adult Rats

BACKGROUND: Maternal care is associated with long-term effects on behavior and epigenetic programming of the NR3C1 (GLUCOCORTICOID RECEPTOR) gene in the hippocampus of both rats and humans. In the rat, these effects are reversed by cross-fostering, demonstrating that they are defined by epigenetic rather than genetic processes. However, epigenetic changes at a single gene promoter are unlikely to account for the range of outcomes and the persistent change in expression of hundreds of additional genes in adult rats in response to differences in maternal care. METHODOLOGY/PRINCIPAL FINDINGS: We examine here using high-density oligonucleotide array the state of DNA methylation, histone acetylation and gene expression in a 7 million base pair region of chromosome 18 containing the NR3C1 gene in the hippocampus of adult rats. Natural variations in maternal care are associated with coordinate epigenetic changes spanning over a hundred kilobase pairs. The adult offspring of high compared to low maternal care mothers show epigenetic changes in promoters, exons, and gene ends associated with higher transcriptional activity across many genes within the locus examined. Other genes in this region remain unchanged, indicating a clustered yet specific and patterned response. Interestingly, the chromosomal region containing the protocadherin-α, -β, and -γ (Pcdh) gene families implicated in synaptogenesis show the highest differential response to maternal care. CONCLUSIONS/SIGNIFICANCE: The results suggest for the first time that the epigenetic response to maternal care is coordinated in clusters across broad genomic areas. The data indicate that the epigenetic response to maternal care involves not only single candidate gene promoters but includes transcriptional and intragenic sequences, as well as those residing distantly from transcription start sites. These epigenetic and transcriptional profiles constitute the first tiling microarray data set exploring the relationship between epigenetic modifications and RNA expression in both protein coding and non-coding regions across a chromosomal locus in the mammalian brain

GABAergic Neuron Deficit As An Idiopathic Generalized Epilepsy Mechanism: The Role Of BRD2 Haploinsufficiency In Juvenile Myoclonic Epilepsy

Idiopathic generalized epilepsy (IGE) syndromes represent about 30% of all epilepsies. They have strong, but elusive, genetic components and sex-specific seizure expression. Multiple linkage and population association studies have connected the bromodomain-containing gene BRD2 to forms of IGE. In mice, a null mutation at the homologous Brd2 locus results in embryonic lethality while heterozygous Brd2+/− mice are viable and overtly normal. However, using the flurothyl model, we now show, that compared to the Brd2+/+ littermates, Brd2+/− males have a decreased clonic, and females a decreased tonic-clonic, seizure threshold. Additionally, long-term EEG/video recordings captured spontaneous seizures in three out of five recorded Brd2+/− female mice. Anatomical analysis of specific regions of the brain further revealed significant differences in Brd2+/− vs +/+ mice. Specifically, there were decreases in the numbers of GABAergic (parvalbumin- or GAD67-immunopositive) neurons along the basal ganglia pathway, i.e., in the neocortex and striatum of Brd2+/− mice, compared to Brd2+/+ mice. There were also fewer GABAergic neurons in the substantia nigra reticulata (SNR), yet there was a minor, possibly compensatory increase in the GABA producing enzyme GAD67 in these SNR cells. Further, GAD67 expression in the superior colliculus and ventral medial thalamic nucleus, the main SNR outputs, was significantly decreased in Brd2+/− mice, further supporting GABA downregulation. Our data show that the non-channel-encoding, developmentally critical Brd2 gene is associated with i) sex-specific increases in seizure susceptibility, ii) the development of spontaneous seizures, and iii) seizure-related anatomical changes in the GABA system, supporting BRD2's involvement in human IGE

Some principles of brain evolution

The evolutionary changes in all parts of the brain occur in gray and white matter. Many changes in the brain stem have resulted in a diverse set of locomotor patterns. The red nucleus in terrestrial vertebrates was differentiated from the tegmentum of fish and amphibians. The red nucleus structure has changed considerably during verte­brate and mammalian development. In lower vertebrates the larger neurons are the predominate form and dur­ing the evolution the number of these neurons diminishes and the number of the small neurons increases con­stantly. The rubrospinal tract progressively declines from lower mammals to primates. This could be linked to the loss of locomotor activity of the upper extremities.The differentiation of respective cortical areas is an important process in the evolution of the cerebral cortex. The common sensorimotor cortex in lower mammals is differentiated into sensory and motor areas. Human speech led to the formation of Broca`s speech area and Wernicke`s area probably half a million years ago. The birth of lit­eracy, about 5000 years ago caused the formation of the Exner`s Writing Area, which is still connected to many other areas of the cerebral cortex and other brain structures

Structural and functional integration between nervous system and immune system

In the last decades were established extensive bidirectional functional and structural communications between nervous and immune system. Neuromediators, cytokines and trophic factors take part in the cell signaling in both systems.The structural interaction occurs by means of sensory and postganglionic sympathetic and parasympathetic fibers. They enter in the lymphoid tissue and organs. In this way is formed the bidirectional interaction between nervous and immune system. This communication exists in health and diseases. The neurotransmitters derived from the nerve fibers regulate the activity of the immune cells by means of their membrane receptors. It is known that T cell-derived cytokines activate and modulate the function of other cells of the immune system. These cytokines influence the activity of the neurons and glial cell in several brain areas as they have membrane cytokine receptors.In the interaction between nervous and immune system has an important role the hypothalamo-pituitary-adrenal axis using glucocorticoids

An aberrant anterior lobe of the left lung in human

In some rare cases the human lung may shows variable accessory fissures that separate aberrant lung lobes. This case report describes an accessory fissure of the left lung of a 67-year-old Caucasian female cadaver that crossed the mediastinal, apical and anterior costal surfaces and thus it separates the organ into a small upper-medial-anterior lung lobe (lobus minimus) from a much larger aberrant lobe (lobus magnus). At the pulmonary hilum the artery, vein and bronchus of the small aberrant lobe were clearly visible. In the field of radiography the existence of such aberrant fissures and lobes have to be known in order to separate between simple anatomic variation of the lungs and a number of lung pathologies