ABSTRACT
Both N-methyl-D-aspartate (NMDA) and quisqualate/AMPA-insensitive metabotropic glutamate (mGlu) receptors mediate glutamate neurotransmission in substantia nigra (SN). In this work, NMDA and mGlu receptor sites in substantia nigra pars compacta (SNC) and pars reticulata were autoradiographically mapped in rat brains using specific binding of (+)3H-MK801 or 3H-glutamate, with saturating concentrations of NMDA, AMPA and quisqualate. In brains of both adult and postnatal day 15 (PN15) male rats, prepared at subjective mid-day of a 12h light/12h dark (12h L/12h D) cycle, specific binding at NMDA and mGlu sites in substantia nigra was pronounced when compared with control binding. The (+)3H-MK801 binding in adults was spatially heterogeneous. Overall binding density in pars compacta was higher relative to binding density in pars reticulata with a mean percent change (Deltaxmacr;%) of 32%. Within the pars reticulata but not pars compacta, there were rostro-caudal differences with considerably denser binding in the posterior compared with the anterior pars reticulata (Deltaxmacr;%=108%). PN15 rats showed a less pronounced heterogeneity in pars compacta versus pars reticulata binding, (Deltaxmacr;%=27%), and less rostro-caudal differentiation in (+)3H-MK801 binding density throughout pars reticulata (Deltaxmacr;%=46%). 3H-glutamate binding in both adult and PN15 rats was less dense overall than (+)3H-MK801 binding. In adults, there was no difference in binding density between pars compacta and pars reticulata (Deltaxmacr;%=0.4%), but there were marked heterogeneities when binding was compared between anterior versus posterior pars compacta (Deltaxmacr;%=29%), and anterior versus posterior pars reticulata (Deltaxmacr;%=25%). This rostro-caudal heterogeneity in 3H-glutamate binding density was also present in PN15 pars compacta (Deltaxmacr;%=45%) but not in pars reticulata. Our findings mirror similar anterior/posterior heterogeneities in the GABAergic system in adult and PN15 male rats and may reflect a developmental change in both the structure and anticonvulsant/proconvulsant properties of substantia nigra pars reticulata (SNR) with age.
Subject(s)
Aging/metabolism , Receptors, Metabotropic Glutamate/metabolism , Receptors, N-Methyl-D-Aspartate/metabolism , Substantia Nigra/metabolism , Animals , Animals, Newborn/growth & development , Animals, Newborn/metabolism , Male , Rats , Rats, Sprague-Dawley , Tissue DistributionABSTRACT
The safety, infectivity, and immunogenicity of two human-bovine reassortant rotavirus candidate vaccines were evaluated in adults, children, and infants. One of these, Wa x UK, contained a single human rotavirus gene from the Wa strain that encoded VP4 P1A specificity in a background of 10 bovine genes including the VP7 gene that encodes G6 specificity, whereas the other, Wa x (DS-1 x UK), possessed the human rotavirus VP4 gene from the Wa strain as well as the human VP7 gene from strain DS-1 that encoded G2 specificity. Each of these vaccines appeared to be well-tolerated and immunogenic in infants less than 6 months of age following a single oral dose, and therefore should be evaluated further as vaccine candidates.
Subject(s)
Antigens, Viral , Capsid Proteins , Rotavirus Vaccines/immunology , Rotavirus/immunology , Administration, Oral , Adolescent , Adult , Animals , Antibodies, Viral/blood , Capsid/genetics , Capsid/immunology , Cattle , Cells, Cultured , Child, Preschool , Chlorocebus aethiops , Dose-Response Relationship, Drug , Double-Blind Method , Humans , Infant , Middle Aged , Recombination, Genetic , Rotavirus/genetics , Rotavirus Infections/immunology , Rotavirus Infections/prevention & control , Rotavirus Vaccines/administration & dosage , Rotavirus Vaccines/adverse effectsABSTRACT
Existe uma crescente controvérsia quanto ao fato das crises convulsivas no período neonatal produzirem ou näo esclerose hipocampal que levaria ao desenvolvimento de uma epilepsia de difícil controle mais tarde na infância ou idade adulta. Nesta revisäo, fazemos um resumo de dados novos baseados em modelos de desenvolvimento da epilepsia. Essas descobertas sugerem que em animais normais, o hipocampo imaturo resiste ao desenvolvimento da esclerose. Esses resultados devem ser considerados quando forem tratados aspectos da intervençäo precoce incluindo cirurgia e tratamento medicamentoso agressivo
