Re-examination of the ontogeny in the gene expression of DARPP-32 in the rat brain

By in situ hybridization histochemistry, we have re-examined the ontogeny of the gene expression of mRNA encoding the dopamine- and cyclic AMP-regulated phosphoprotein with a molecular weight of 32,000, termed DARPP-32. On E13 and E15, weak expression signals were detected in the mantle zones and ventricular germinal zones of the fore-, mid-, hind-brain, and spinal cord. In the caudate putamen, the expression signals were first visible at its lateral margin on E15. The ventrolateral region of the caudate putamen expressed the gene intensely, while its ventricular germinal zone expressed it weakly on E18-20. Thereafter, the mRNA for DARPP-32 were expressed over the entire caudate putamen in patchy patterns. After birth, the expression levels in the caudate putamen increased markedly, with the majority of the neurons in the caudate putamen expressing the gene intensely on P7 and thereafter. In addition to the caudate putamen, expression signals were detected, albeit faintly, in the olfactory bulb, cortical plate, hippocampal pyramidal cell layer, and their ventricular zones on E18-20. The olfactory tubercle and medial habenular nucleus expressed the gene at slightly higher levels. In the cerebellum, the Purkinje cells showed progressively increasing gene expression from E20 to P7, whereas the external granule cell layer expressed the gene weakly. The ontogeny of the gene expression is largely consistent with previous immunohistochemical findings by other authors. Furthermore, the present finding suggests that DARPP-32 is involved in the regulation of the mitosis-related dephosphorylation by protein phosphatase 1 in the neuroepithelium.     

Decreased expression and functionality of NMDA receptor complexes persist in the CA1, but not in the dentate gyrus after transient cerebral ischemia

The authors investigated the gene expression of the NR2A and NR2B subunits of N-methyl-D-aspartate (NMDA) receptor and the functional electrophysiologic activity of NMDA receptor complexes in the vulnerable CA1 and less vulnerable dentate gyrus subfields of the rat hippocampus at different times after transient cerebral ischemia. Decreased expression for both subtypes was observed in both the CA1 subfield and dentate granule cell layer at early times after challenge; however, the decreased expression in the dentate granule cell layer was reversible because mRNA levels for both the NR2A and NR2B subtypes recovered to, or surpassed, sham-operated mRNA levels by 3 days postchallenge. No recovery of expression for either subtype was observed in the CA1 subfield. The functional activity of NMDA receptor complexes, as assessed by slow field excitatory postsynaptic potentiations (slow f-EPSP) in CA1 pyramidal neurons, was maintained at 6 hours postchallenge; however, this activity was diminished greatly by 24 hours postchallenge, and absent at 7 days postchallenge. A similar pattern was observed for the non-NMDA receptor-mediated fast f-EPSP. In dentate granule neurons, however, no significant change in NMDA receptor-mediated slow f-EPSP from sham control was observed at any time after insult. The non-NMDA receptor-generated fast f-EPSPs also were maintained at all times postinsult in the dentate gyrus. These results illustrate that the activity of NMDA receptors remains functional in dentate granule neurons, but not in the pyramidal neurons of the CA1 subfield, at early and intermediate times after transient cerebral ischemia, and suggest that there is a differential effect of ischemia on the glutamatergic transmission systems in these two hippocampal subfields.     

Postnatal development of zinc-containing cells and neuropil in the hippocampal region of the mouse

The present study describes the postnatal development of zinc-containing boutons and their neurons of origin in the hippocampal region of the mouse. Ages investigated for the development of zinc-containing neuropil were postnatal days 0 (P0), P3, P7, P11, P15, P21, and P28. For zinc-containing cell bodies P7, P15, P21, and P28 were studied. In the area dentata, zinc-containing neuropil appeared first by P3 adjacent to the suprapyramidal limb of the granule cell layer and extended later toward the infrapyramidal limb. By P15, inter- and intralaminar gradients corresponded to those seen in adult animals. The appearance of labeled granule cells followed closely, although temporally delayed, the pattern of granule cell neurogenesis. All granule cells were labeled by P28. In the hippocampus proper, zinc-containing neuropil was seen by P0, but staining of the incipient mossy fiber zone was first visible by P3. Staining pattern and intensity developed gradually until they reached their mature appearance by P15. The distribution of labeled cells was identical to that seen in mature animals by P7 in CA3, but first by P21 in CA1. In the subiculum, neuropil staining first appeared proximally by P7, included all of this area by P11, and appeared mature by P21. A few labeled cells were seen in the proximal subiculum at all ages at which labeled cells were present in CA1. Labeled cells which extended further distally became first visible by P21. Their number and labeling intensity reached mature levels by P28. In the presubiculum, retrosplenial area 29e, and parasubiculum, neuropil staining first appeared by P3. The retrosplenial area 29e could be distinguished by P11. This area and the presubiculum reached their adult appearance by P21. This occurred first by P28 in the parasubiculum due to the late maturation of the parasubiculum a. Labeled cells were first seen by P7 in layer III of the presubiculum and by P15 in the retrosplenial area 29e and the parasubiculum. Cell labeling appeared mature by the same times as the neuropil staining. In the entorhinal areas a very light neuropil stain was apparent in the deeper layers by P0. A distinct rise in staining intensity was first observed by P7 in layers I-III. Thereafter, mature characteristics developed gradually and were attained by P21. Cell labeling was not seen in the medial entorhinal area. A few labeled cells were apparent by P7 in the lateral entorhinal area. After a slight increase by P15, numerous labeled cells were found in layer II and layer VI by P21. Their distribution and labeling intensity appeared mature by P28. Zinc-containing cells appear to represent cells formed late in the course of neurogenesis in all areas aside from the lateral entorhinal area. As far as intrinsic connections are concerned, it is the development of projections from this subset of neurons which is monitored in this study. We suggest that the appearance of zinc may contribute via its different effects on N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors to the end of a developmental phase that is permissive to changes in synaptic efficacy. Species differences and alternative functions of zinc are considered.     

Oxidative alterations in Alzheimer's disease

The expression of heparin-binding epidermal growth factor-like growth factor (HB-EGF), an EGF receptor ligand, was investigated in rat forebrain under basal conditions and after kainate-induced excitotoxic seizures. In addition, a potential neuroprotective role for HB-EGF was assessed in hippocampal cultures. In situ hybridization analysis of HB-EGF mRNA in developing rat hippocampus revealed its expression in all principle cell layers of hippocampus from birth to postnatal day (P) 7, whereas from P14 through adulthood, expression decreased in the pyramidal cell layer versus the dentate gyrus granule cells. After kainate-induced excitotoxic seizures, levels of HB-EGF mRNA increased markedly in the hippocampus, as well as in several other cortical and limbic forebrain regions. In the hippocampus, HB-EGF mRNA expression increased within 3 hr after kainate treatment, continued to increase until 24 hr, and then decreased; increases occurred in the dentate gyrus granule cells, in the molecular layer of the dentate gyrus, and in and around hippocampal pyramidal CA3 and CA1 neurons. At 48 hr after kainate treatment, HB-EGF mRNA remained elevated in vulnerable brain regions of the hippocampus and amygdaloid complex. Western blot analysis revealed increased levels of HB-EGF protein in the hippocampus after kainate administration, with a peak at 24 hr. Pretreatment of embryonic hippocampal cell cultures with HB-EGF protected neurons against kainate toxicity. The kainate-induced elevation of [Ca2+]i in hippocampal neurons was not altered in cultures pretreated with HB-EGF, suggesting an excitoprotective mechanism different from that of previously characterized excitoprotective growth factors. Taken together, these results suggest that HB-EGF may function as an endogenous neuroprotective agent after seizure-induced neural activity/injury.     

Immunohistochemical localization of G protein beta1, beta2, beta3, beta4, beta5, and gamma3 subunits in the adult rat brain

The regional distributions of the G protein beta subunits (Gbeta1-beta5) and of the Ggamma3 subunit were examined by immunohistochemical methods in the adult rat brain. In general, the Gbeta and Ggamma3 subunits were widely distributed throughout the brain, with most regions containing several Gbeta subunits within their neuronal networks. The olfactory bulb, neocortex, hippocampus, striatum, thalamus, cerebellum, and brainstem exhibited light to intense Gbeta immunostaining. Negative immunostaining was observed in cortical layer I for Gbeta1 and layer IV for Gbeta4. The hippocampal dentate granular and CA1-CA3 pyramidal cells displayed little or no positive immunostaining for Gbeta2 or Gbeta4. No anti-Gbeta4 immunostaining was observed in the pars compacta of the substantia nigra or in the cerebellar granule cell layer and Purkinje cells. Immunoreactivity for Gbeta1 was absent from the cerebellar molecular layer, and Gbeta2 was not detected in the Purkinje cells. No positive Ggama3 immunoreactivity was observed in the lateral habenula, lateral septal nucleus, or Purkinje cells. Double-fluorescence immunostaining with anti-Ggamma3 antibody and individual anti-Gbeta1-beta5 antibodies displayed regional selectivity with Gbeta1 (cortical layers V-VI) and Gbeta2 (cortical layer I). In conclusion, despite the widespread overlapping distributions of Gbeta1-beta5 with Ggamma3, specific dimeric associations in situ were observed within discrete brain regions.     

Influence of renal failure on the pharmacokinetics and neuromuscular effects of a single dose of rapacuronium bromide

Neurotransmitter transporters are involved in termination of the synaptic neurotransmission and are implicated as the sites of action of antidepressant medicines and illicit drugs. In addition to their function in neurotransmission, neurotransmitter transporters play a key role in neuroregulation and brain development. In this report, the developmental distribution of the "orphan" transporter NTT4, whose substrate has not yet been shown, is described. Immunohistochemical studies have previously shown NTT4 to be specifically and widely localized to the central nervous system. In this report, the distribution of NTT4 in brain areas enriched in glutamatergic and gamma-aminobutyric acid-ergic innervations is further substantiated. NTT4 is detected beginning at E18 in various parts of the rat brain, including the cerebral cortex, fimbria hippocampi, fornix, lateral lemniscus, anterior commissure, and spinal cord. At E18, strong immunoreactivity of NTT4 is observed in the cortical subplate and marginal layers that later develops into the fimbria hippocampi, and at P22, the expression of NTT4 in the hippocampal formation reaches the mature form. The expression of NTT4 in the spinal cord begins at E18 in the ventral white matter. Heavy staining for NTT4 is observed in the substantia nigra since birth and through all time points examined. Transient immunoreactivity is observed in the inferior colliculus, reaching maximal expression at P10, whereas the superior colliculus commences to express NTT4 only after this time point. The globus pallidus is highly stained after birth, and the caudate putamen shows strong staining for NTT4 only at P22. In the adult rat brain, NTT4 is strongly expressed in the olfactory bulb, cerebral cortex, striatum, hippocampus, thalamus, substantia nigra, pontine nucleus, cerebellum, and spinal cord. The developmental distribution of NTT4 suggests involvement in central nervous system maturation.     

Effective peer responses to impaired nursing practice

Subplate neurons, the first neurons of the cerebral cortex to differentiate and mature, are thought to be essential for the formation of connections between thalamus and cortex, such as the system of ocular dominance columns within layer 4 of visual cortex. To learn more about the requirement for subplate neurons in the formation of thalamocortical connections, we have sought to identify the neurotransmitters and peptides expressed by the specific class of subplate neurons that sends axonal projections into the overlying visual cortex. To label retrogradely subplate neurons, fluorescent latex microspheres were injected into primary visual cortex of postnatal day 28 ferrets, just prior to the onset of ocular dominance column formation. Subsequently, neurons were immunostained with antibodies against glutamate, glutamic acid decarboxylase (GAD-67), parvalbumin, neuropeptide Y (NPY), somatostatin (SRIF), or nitric oxide synthase (NOS). Retrograde labeling results indicate that the majority of subplate neurons projecting into the cortical plate reside in the upper half of the subplate. Combined immunostaining and microsphere labeling reveal that about half of cortically projecting subplate neurons are glutamatergic; most microsphere-labeled subplate neurons do not stain for GAD-67, parvalbumin, NPY, SRIF, or NOS. These observations suggest that subplate neurons can provide a significant glutamatergic synaptic input to the cortical plate, including the neurons of layer 4. If so, excitation from the axons of subplate neurons may be required in addition to that from lateral geniculate nucleus neurons for the activity-dependent synaptic interactions that lead to the formation of ocular dominance columns during development.     

Expression of GABA(A) receptor subunits in the hippocampus of the rat after kainic acid-induced seizures

The GABA(A) receptor is a ligand gated chloride channel consisting of five membrane spanning proteins for which 13 different genes have been identified in the mammalian brain. The present review summarizes recent work from our laboratory on the characterization of the immunocytochemical distribution of these GABA(A) receptor subunits in the rat brain and changes in immunoreactivity and mRNA expression after kainic acid-induced status epilepticus. A heterogeneous distribution of immunoreactive GABA(A) receptor subunits was observed. The most abundant ones were: alpha1, alpha2, alpha4, alpha5, beta2, beta3, gamma2, and delta. Alpha1, beta2, and gamma2 were about equally distributed in all subfields of the hippocampus; alpha4- and delta-subunits were preferentially found in the dentate molecular layer and in CA1; alpha2 was localized to the dentate molecular layer and CA3; alpha5 was found in the dendritic areas of CA1 to CA3; and beta1 was preferentially seen in CA2. Alpha1, beta2, gamma2 and delta were highly concentrated in interneurons. Kainic acid-induced seizures caused acute and chronic changes in the expression of mRNAs and immunoreactive proteins. Acute changes included decreases in alpha2, alpha5, beta1, beta3, gamma2 and delta mRNA levels (by about 25-50%), accompanied by increases (by about 50%) in alpha1, alpha4, and beta2 messages in granule cells (after 6-12 h). Chronic changes, characterized by losses in mRNA and immunoreactive proteins in CA1 and CA3, are undoubtedly due to seizure-related cell damage. However, compensatory expression of alpha2 and beta3 subunits, especially in CA3b/c, was observed. Furthermore, increases in mRNAs and immunoreactive proteins were seen for alpha1, alpha2 alpha4, beta1, beta2, beta3 and gamma2 in granule cells and in the molecular layer of the dentate gyrus at 7-30 days after kainic acid injection. The changes in the expression of GABA(A) receptor subunits, observed in practically all hippocampal subfields, may reflect altered GABA-ergic transmission during development of the epileptic syndrome. Increased expression of GABA(A) receptor subunits in the dendritic field of granule cells and CA3 suggest that GABA-ergic inhibition may be augmented at these levels. However, the lasting preservation of alpha1-, beta2-, and gamma2-subunits in interneurons could provide a basis for augmented inhibition of GABA-ergic interneurons, leading to net disinhibition.     

Id1, Id2, and Id3 gene expression in neural cells during development

Id1, Id2, and Id3 mRNA are expressed mainly in the proliferating ependymal cell zone of the mouse brain during embryogenesis. In this study, the expression pattern and cell phenotypes of the Id family mRNA were examined in postnatal and adult rat brain. The expression of Idl and Id3 mRNA in rat brain was observed in the cortex layer 1, corpus callosum, ventricular/subventricular zone (VZ/ SVZ), and the CA1-4 layers of the hippocampus at postnatal day 1 (P1) through P14, whereby it declined at 2 months. In general, the developmental pattern of Idl mRNA coincided with the pattern observed for Id3 mRNA. Similar to Id1 and Id3, Id2 mRNA was highly expressed in the corpus callosum, VZ/SVZ, and the hippocampus. Examination of Id2 mRNA revealed high levels in the cortex and caudate putamen at P1 through P14, whereas a decline was observed in its expression in the adult cortex. In P5 rat cerebellum, all Id mRNA examined were found in the internal granular cell layers; however, at this time point, only Id2 mRNA expression was detected in the differentiating zone of the external granular cell layers, preferentially localizing to adult Purkinje cells. Furthermore, only Id2 mRNA expression in brain was observed in NF+ neurons at P5. Examination of S100alpha+ and GFAP+ astrocytes, revealed the presence of all three mRNAs, whereas the expression of Id2 and Id3 mRNA was absent in 04+ immature oligodendrocytes. These data suggest that the spatial and temporal kinetic patterns during development, as well as cellular specificity, of the Id gene family may play a critical role in neural precursor cell proliferation and cell divergence.     

Degradation of cytokeratin intermediate filaments by calcium-activated proteases (calpains) in vitro: implications for formation of Mallory bodies

A replication defective adenoviral vector containing the E. coli lacZ gene (AdCMVnLacZ) was directly injected into right hippocampus and lateral ventricle immediately after 5 min of transient global ischemia in gerbils. The relations between the lacZ gene expression and DNA fragmentation or heat shock protein 72 (HSP72) immunoreactivity were examined up to 21 days post ischemia. The lacZ gene was transiently expressed at 1 day in the hippocampus except around the CA1 region, while a large number of the periventricular cells strongly expressed the lacZ gene from 8 h to 7 days. In CA1 layer, terminal deoxynucleotidyl dUTP nick end labeling (TUNEL) positive cells, which were present only adjacent to the needle track at 8 h to 1 day, became more extensive in the whole CA1 layer at 3 to 7 days. TUNEL-positive cells were also detected around the DG at 1 day, around the needle track at 8 h to 3 days, and in the choroid plexus cells at 7 days. HSP72 staining was detected in the subiculum at 1 to 3 days, the dentate granule cells at 8 h to 1 day, and in the CA3 or CA4 pyramidal cells at 1 to 3 days. Some lacZ expressing cells were double-positive with HSP72 in DG, while the majority of those were distinguished from the TUNEL-positive cells. Pyramidal neurons were almost completely lost in the CA1 sector at 7 days after the ischemia. The present study demonstrates the successful LacZ gene transfer into the hippocampus and ventricle of postischemic gerbil brain except in the vulnerable CA1 layer by adenoviral vector injection. However, adenovirus-mediated gene transfer may induce indirect apoptotic cell death in the DG and ventricle, in addition to direct traumatic injury around the needle track.     

Forebrain ischemia in the gerbil increases lambda opiate binding in hippocampal mossy fibers

Transient forebrain ischemia was produced in gerbils by short-term occlusion of the common carotid arteries under halothane anesthesia. Histological analysis of brains 7 days post-ischemia demonstrated characteristic destruction of CA1 pyramidal cells. lambda Opiate binding (measured with [3H]naloxone in the presence of 300 nM diprenorphine) at 7 days post-ischemia was significantly increased in the stratum lucidum of the hippocampus (the mossy fiber layer), but not in any other region measured, including other hippocampal regions, cortex, amygdala, caudate putamen, thalamus, and hypothalamus. The increase in mossy fiber lambda binding was slow to develop (no increase detected up to 48 h post-ischemia), and long-lasting (binding remained elevated at 32 days post-ischemia). While MK-801 significantly inhibited CA1 pyramidal cell destruction when administered 20 min prior to ischemia, the increase in mossy fiber lambda binding was still evident. None of seven different opioid agonists and antagonists examined had an effect on either the pyramidal cell damage or increased mossy fiber lambda binding seen 7 days after ischemia.     

Increased neurogenesis in the dentate gyrus after transient global ischemia in gerbils

Neurogenesis in the dentate gyrus of adult rodents is regulated by NMDA receptors, adrenal steroids, environmental stimuli, and seizures. To determine whether ischemia affects neurogenesis, newly divided cells in the dentate gyrus were examined after transient global ischemia in adult gerbils. 5-Bromo-2'-deoxyuridine-5'-monophosphate (BrdU) immunohistochemistry demonstrated a 12-fold increase in cell birth in the dentate subgranular zone 1-2 weeks after 10 min bilateral common carotid artery occlusions. Two minutes of ischemia did not significantly increase BrdU incorporation. Confocal microscopy demonstrated that BrdU immunoreactive cells in the granule cell layer colocalized with neuron-specific markers for neuronal nuclear antigen, microtubule-associated protein-2, and calbindin D28k, indicating that the newly divided cells migrated from the subgranular zone into the granule cell layer and matured into neurons. Newborn cells with a neuronal phenotype were first seen 26 d after ischemia, survived for at least 7 months, were located only in the granule cell layer, and comprised approximately 60% of BrdU-labeled cells in the granule cell layer 6 weeks after ischemia. The increased neurogenesis was not attributable to entorhinal cortical lesions, because no cell loss was detected in this region. Ischemic preconditioning for 2 min, which protects CA1 neurons against subsequent ischemic damage, did not prevent increased neurogenesis in the granule cell layer after a subsequent severe ischemic challenge. Thus, ischemia-induced dentate neurogenesis is not attributable to CA1 neuronal loss. Enhanced neurogenesis in the dentate gyrus may be a compensatory adaptive response to ischemia-associated injury and could promote functional recovery after ischemic hippocampal injury.     

The development of parvalbumin and calbindin-D28k immunoreactive interneurons in kitten visual cortical areas

Calbindin-D and parvalbumin are calcium binding proteins which are found in non-overlapping subpopulations of GABA-ergic interneurons in mammalian neocortex. We studied the development of these calcium-binding proteins in interneurons of cat striate and extrastriate cortical areas which have differing patterns of connectivity and follow different developmental timetables. We examined primary visual areas 17 and 18, secondary visual area 19, medial lateral suprasylvian and lateral suprasylvian areas (MLS and LLS) and association areas 7 and the splenial visual area from the day of birth (P0) through P101. Parvalbumin-immunoreactive (ir) interneurons followed the inside-out pattern of maturation of cortical laminae. They were located only in infragranular layers at the earliest ages and were not observed in the overlying cortical plate. At 3 weeks of age, when cortical lamination is mature, parvalbumin stained cells were found in all cortical layers except layer I. The number of stained secondary and tertiary dendrites in the parvalbumin-ir interneuronal population decreased with age. This change was associated with a shift in the molecular weight of parvalbumin detected on Western blots. During the first postnatal week, the area 17/18 border contained more parvalbumin-ir neurons than other visual areas. The developmental pattern of calbindin staining differed considerably from the parvalbumin staining pattern. Very few calbindin-ir interneurons were seen in area 17 during the first 2 weeks of life. In lateral cortical areas, calbindin-ir neurons were located in cortical plate, infragranular layers of cortex and white matter/subplate. Calbindin-ir neurons increased in supragranular layers of secondary cortical areas by P7 and in area 17 by P20. In the mature cortex, the calbindin staining pattern was bilaminar, with a dense band of calbindin-ir cells in layer II and a second band in layers V-VI. There was no difference in the distribution of calbindin-ir neurons among visual areas at maturity.     

Transient neurophysiological changes in CA3 neurons and dentate granule cells after severe forebrain ischemia in vivo

Transient neurophysiological changes in CA3 neurons and dentate granule cells after severe forebrain ischemia in vivo. J. Neurophysiol. 80: 2860-2869, 1998. The spontaneous activities, evoked synaptic responses, and membrane properties of CA3 pyramidal neurons and dentate granule cells in rat hippocampus were compared before ischemia and 相似文献   

Tissue plasminogen activator mRNA expression in granule neurons coincides with their migration in the developing cerebellum

Tissue plasminogen activator activity in the developing cerebellum, as quantified by zymography of cerebellar homogenates from embryonic day (E) 17 to adult mice, shows a peak of activity at postnatal day (P) 7, followed by a steady 75% decrease into adulthood. Northern blot analysis reveals a similar pattern for tissue plasminogen activator mRNA levels, which are low at E17 but increase dramatically, reaching their highest levels of specific mRNA/micrograms RNA in P1-P7 mice and declining about threefold in the adult mouse. In situ hybridization of whole mouse brain sections with a tissue plasminogen activator antisense cRNA probe shows pronounce reactivity in the cerebellum. Although some binding is associated with the cerebellar meninges, the external granule layer is devoid of tissue plasminogen activator mRNA at all ages. However, highly labeled elongated cells, which also bind antibody to neuronal nuclear antigen and are adjacent to Bergmann glial fibers (i.e., migrating granule neurons), are readily visible throughout the molecular and Purkinje layers at P7 and P14. In the adult mouse cerebellum, tissue plasminogen activator mRNA labeling is restricted to cells in the Purkinje/internal granule layers. Thus, tissue plasminogen activator gene expression is induced as granule neurons leave the external granule layer and begin their inward migration.     

GABAergic cells are the major postsynaptic targets of mossy fibers in the rat hippocampus

Dentate granule cells communicate with their postsynaptic targets by three distinct terminal types. These include the large mossy terminals, filopodial extensions of the mossy terminals, and smaller en passant synaptic varicosities. We examined the postsynaptic targets of mossy fibers by combining in vivo intracellular labeling of granule cells, immunocytochemistry, and electron microscopy. Single granule cells formed large, complex "mossy" synapses on 11-15 CA3 pyramidal cells and 7-12 hilar mossy cells. In contrast, GABAergic interneurons, identified with immunostaining for substance P-receptor, parvalbumin, and mGluR1a-receptor, were selectively innervated by very thin (filopodial) extensions of the mossy terminals and by small en passant boutons in both the hilar and CA3 regions. These terminals formed single, often perforated, asymmetric synapses on the cell bodies, dendrites, and spines of GABAergic interneurons. The number of filopodial extensions and small terminals was 10 times larger than the number of mossy terminals. These findings show that in contrast to cortical pyramidal neurons, (1) granule cells developed distinct types of terminals to affect interneurons and pyramidal cells and (2) they innervated more inhibitory than excitatory cells. These findings may explain the physiological observations that increased activity of granule cells suppresses the overall excitability of the CA3 recurrent system and may form the structural basis of the target-dependent regulation of glutamate release in the mossy fiber system.     

Functional changes in THP-1 human monocytic cells after stimulation with lipopolysaccharide of oral microorganisms and granulocyte macrophage colony stimulating factor

Two major classes of early-born neurons are distinguished during early corticogenesis in the rat. The first class is formed by the cortical pioneer neurons, which are born in the ventricular neuroepithelium all over the cortical primordium. They appear at embryonic day (E) 11.5 in the lateral aspect of the telencephalic vesicle and cover its whole surface on E12. These cells, which show intense immunoreactivity for calbindin and calretinin, are characterized by their large size and axonal projection. They remain in the marginal zone after the formation of the cortical plate; they project first into the ventricular zone, and then into the subplate and the internal capsule. Therefore, these cells are the origin of the earliest efferent pathway of the developing cortex. Pioneer neurons are only present in prenatal brains. The second class is formed by subpial granule neurons, which form the subpial granular layer (SGL), previously considered to be found exclusively in the human cortex. SGL neurons are smaller than pioneer neurons. They are generated in a transient compartment of the retrobulbar ventricle between E12 and E14, and we propose the hypothesis that they invade the marginal zone, through tangential subpial migration, at different moments of fetal life. SGL neurons contain calbindin, calretinin, and gamma-aminobutyric acid (GABA), but the GABA-immunoreactive group becomes inconspicuous before birth. The extracellular matrix-like glycoprotein reelin, a molecule crucial for cortical lamination, is prenatally expressed by SGL neurons; postnatally, it is present in both Cajal-Retzius cells and subpial pyriform cells, both derivatives of SGL cells. In the rat, Cajal-Retzius cells are horizontal neurons that remain only until the end of the first postnatal week. They are located in layer I at a critical distance of approximately 20 microm from the pial surface and express reelin and, only occasionally, calretinin. Subpial pyriform cells coexpress reelin and calretinin and remain in layer I longer than Cajal-Retzius cells. Both pioneer neurons and subpial granule neurons are specific to the cortex. They mark the limit between the rudimentary cerebral cortex and olfactory bulb in the rat during early corticogenesis.