Hilar Region Of Dentate Gyrus Research Articles

Influence of hypo-osmolality and induced seizures on blood brain barrier permeability and brain concentrations of trace elements in rats

Backgrounds: We studied the changes in blood-brain barrier (BBB) permeability and brain trace elements concentration in acute hypo-osmolality and pentylenetetrazol (PTZ)-induced seizures model in rats. Furthermore, the effect of acute hypo-osmolality on seizure activity (patterns) in the PTZ model, the correlation between seizure severity score (SS score) and changes of both of BBB permeability and brain trace elements concentration in rats were also studied. Materials and Methods: Four groups (18 animals /group) of adult male albino rats were included. The animal groups are: (1) Control group: received only a vehicle. (2) Hypo-osmolar group: received warm distilled water (DW). (3) Seizure group: injected with PTZ i.p. (4) Hypo-osmolar + seizure group: first injected with DW and then PTZ. During the next 30 minutes, the animals were observed for seizure activity. For evaluation of BBB permeability changes, serum S100B protein and Evan Blue (EB) dye content of brain tissue were evaluated. Additionally macroscopic and microscopic examinations of brain tissue were completed. Trace elements, magnesium (Mg), zinc (Zn), copper (Cu) and iron (Fe), concentration in brain tissue were estimated. Results: There were significant increase of EB content of brain tissue, and serum S100ß in hypo-osmolar, seizure and hypo-osmolar + seizure groups, as compared with control animals. These parameters were significantly increased in the hypo-osmolar + seizure group when compared with either hypo-osmolar or seizure groups. These results were confirmed by macroscopic examination of brain tissue. Trace elements concentration of brain tissue, Mg, Zn, Cu and Fe, were significantly decreased in hypo-osmolar, seizure and hypo-osmolar + seizure groups in comparison with control animals. Histological examination of sections from the hilar region of dentate gyrus of the hippocampus revealed degenerative changes in the three groups of animals in comparison with control animals. Morphometric analysis showed a significant decrease in the number of cells in the hilar region of dentate gyrus in the three groups of animals in comparison with controls. Seizure activity significantly increased in hypo-osmolar + seizure as compared to seizure group. The correlation analysis revealed that significant −ve correlations were found between SS score and trace elements concentration, while significant +ve correlations were observed between SS score, and each of EB content and serum S100ß protein in seizure and hypo-osmolar + seizure groups. Conclusion: Our study demonstrated that, hypo-osmolality and PTZ-induced seizures could result in increased BBB permeability with a decrease of brain trace elements concentration. This could play a vital role in the pathophysiology of epileptic seizures. In addition, hypo-osmolality can enhance neuronal excitability and severity of seizures in the PTZ-induced model in rats.

MGluR-mediated and endocannabinoid-dependent long-term depression in the hilar region of the rat dentate gyrus

We report that bath application of the group I mGluR agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) causes acute inhibition of evoked IPSCs recorded from hilar mossy cells, and that significant long-term depression (LTD) of synaptic transmission remains following washout of DHPG. Subsequent experiments using minimal stimulation techniques revealed that expression of both acute and long-term effects of DHPG are restricted to a subset of GABAergic afferents that are also sensitive to depolarization-induced suppression of inhibition (DSI). Experiments with a selective CB1 antagonist and with transgenic animals lacking CB1 receptors indicate that all effects of DHPG, like DSI, depend on activation of CB1 receptors. Further work with selective mGluR antagonists suggests a direct involvement of mGluR1 receptors. Interestingly, we also report that induction of LTD under our experimental conditions does not require prior direct somatic depolarization via the patch pipette and does not appear to depend critically on the level of activity in incoming GABAergic afferents. Collectively, these results represent the first characterization of mGluR-mediated and endocannabinoid-dependent LTD in the hilar region of the dentate gyrus. The dentate gyrus is thus one of relatively few areas where this mechanism has clearly been demonstrated to induce long-term modulation of inhibitory synaptic transmission.

Gene transfer patterns and transduction efficacy of recombinant adeno-associated virus type 1, 2, and 5 in brain: an experiment with rats

To investigate the gene transfer patterns and transduction efficacy of different serotypes of recombinant adeno-associated virus (rAAV): rAAV1, 2, and 5 in brain. Fifty-four adult male SD rats were randomly divided into 9 equal groups to be injected with titre and volume-matched rAAV1, rAAV2, and rAAV5 carrying enhanced green fluorescent protein (EGFP) reporter gene into the hippocampus, lateral ventricle, and cortex respectively. Eight weeks later the rats were killed and their brains taken out. Fluorescent microscopy was used to observe the expression of EGFP in the brain. Real-time reverse transcriptase PCR was carried out to quantitate the EGFP expression. In the intra-hippocampal injection groups, the expression of rAAV1-EGFP was significantly stronger than those of rAAV2 and rAAV5 (both P < 0.01). Spread to the whole CA1 and CA2 areas, and the greater part of the CA3 area, the expression of rAAV1 was seen in the most of pyramidal cells and their projections. The expression of rAAV2-EGFP was limited in the multiform cell layer of the hilar region of dentate gyrus; whereas the rAAV5-EGFP expression was sparsely distributed in the structures around the injection sites. In both the intra-ventricular and intra-cortical groups only rAAV1-EGFP was expressed in many structures around the lateral ventricle, such as hippocampus, lateral septal nucleus, and striate body, and around the injection sites in cortex, and diffused to the callus in a small amount; and rAAV2 and rAAV5 were not expressed. More effective in transduction, rAAV1 is a more effective gene-transferring vector to be used in different disorders of the central nervous system.

GABA A, not GABA B, receptor shows subunit- and spatial-specific alterations in the hippocampus of seizure prone gerbils

In the present study, we investigated site-specific expressions of GABA A and GABA B receptor subunits in the seizure-sensitive (SS) and seizure-resistant (SR) gerbil hippocampus to elucidate the function of the γ-aminobutyric acid (GABA) receptor in seizure activity in this animal. There were no differences of the immunoreactivities of GABA B receptor and some GABA A receptor subunits (α3, α4, pan β and δ) in the hippocampus between SR and SS gerbils. The α1 subunit expression was mainly detected in interneurons of stratum radiatum and hilar region of dentate gyrus in the SR gerbil. However, in SS gerbil, interneurons were nearly devoid of α1 subunit immunoreactivity and mainly detected in the molecular layer of dentate gyrus. In SR gerbil, α2 subunit immunoreactivity was detected in Ammon's horn, particularly in the CA2 region. In SS gerbil, granule cell layer of the dentate gyrus in SS gerbil showed strong α2 subunit immunoreactivity. The distribution of α5 and γ2 subunit immunoreactivity in the hippocampus was similarly detected in SR and SS gerbil. However, α5 immunodensity of SR gerbil was slightly lower than that of SS gerbil in CA1 region and was slightly strong than that of SS gerbil in subiculum. These differences in distribution of GABA A receptor, not GABA B receptor, in the SR and SS gerbil hippocampus may indicate that abnormal hyperactive neuronal discharges are occurred in SS gerbil, which presumably result in spontaneous and repetitive seizure activity in this animal.

TRK and p75 neurotrophin receptor systems in the developing human brain

The prenatal development of the neurons immunoreactive for high-affinity tropomycin-related kinase (trk) receptor (pan trk which recognizes trkA, trkB, and trkC) and low-affinity p75 neurotrophin receptor (p75NTR) was examined in the human brain from embryonic weeks 10 to 34 of gestation. In the embryonic week 10 specimen in which only brainstem regions were available for evaluation, trk immunoreactivity (trk-ir) was observed in the ventral cochlear, solitary, raphe, spinal trigeminal, and hypoglossal nuclei, as well as the vestibular complex and medullary reticular formation. At this time point of gestation, p75ntr-immunoreactive (p75NTR-ir) staining was observed within these same regions plus the inferior olivary and ambiguus nuclei. At embryonic week 14, trk-ir neurons were seen within the subplate zone of the entorhinal cortex, basal forebrain, caudate nucleus, putamen, external segment of the globus pallidus, specific thalamic nuclei, lateral mammillary nucleus, habenula nucleus, select brainstem nuclei, and the dentate nucleus of cerebellum. At this gestational time point, p75NTR-ir neurons were observed in each of these structures, with the exception of the caudate nucleus, specific thalamic nuclei, lateral mammillary nucleus, and habenula nucleus. Additionally, p75NTR-ir neurons were observed within the corpus callosum. The staining pattern for both trk and p75NTR remained unchanged at embryonic weeks 15 to 16 except for the addition of trk-ir and p75NTR-ir within the cortical subplate zone, hippocampus, and subthalamic nucleus. By embryonic week 18, trk-ir neurons were widely expressed within mostly all thalamic nuclei. In contrast, trk-ir was no longer seen within the hypoglossal, cuneate, and gracile nuclei at this time point. This staining pattern for trk and p75NTR remained virtually unchanged from embryonic weeks 19 to 20 and embryonic weeks 16 to 20, respectively. From embryonic weeks 22 to 34, the distribution of both trk-ir and p75NTR-ir neurons changed gradually. During this period, neurons in most thalamic and some brainstem nuclei became progressively immunonegative for trk, whereas neurons in the neocortical subplate zone, corpus callosum, and hilar region of dentate gyrus gradually lost immunoreactivity for p75NTR. These data demonstrate an important and complex role for both the high-(trk) and low- (p75) affinity neurotrophin receptors during the development of multiple neuronal systems in the human brain.

Immunohistochemical distribution of calcium‐activated neutral proteinases and endogenous CANP inhibitor in the rabbit hippocampus

Intracellular accumulation of Ca2+ after brain ischemia is regarded as one of the principal causes of neuronal death, but details of the intracellular events occurring after Ca2+ accumulation have not yet been described. We propose that a calcium-activated neutral proteinase which can degrade neuronal cytoskeletal proteins might link Ca2+ accumulation and irreversible injury of the neuronal intracellular structure. First, therefore, we examined the distribution of calcium-activated neutral proteinase in normal brains. Immunohistochemical distribution of calcium-activated neutral proteinases (CANP) with high and low sensitivity to Ca2+ (muCANP and mCANP) and of endogenous CANP inhibitor was investigated in the dorsal hippocampus of the rabbit. muCANP-immunoreactivity was detected in almost all of the pyramidal cells and granule cells and in some other neurons. A full-length staining from perikarya to dendrites was shown in muCANP-positive neurons. mCANP-immunoreactivity was found mainly in four kinds of hippocampal interneurons: 1) basket cells in the stratum oriens of Ammon's horn, 2) pyramidal basket cells at the boundary of pyramidal cell layer and stratum oriens, 3) polymorphic cells in the hilar region of dentate gyrus, and 4) pyramidal or fusiform basket cells at the inner boundary of the granule cell layer and the hilar region. The distribution of these four kinds of neurons was similar to that of parvalbumin-containing GABAergic neurons. CANP inhibitor immunoreactivity was confined to pyramidal cells in the CA3-CA3c region and some hilar neurons.(ABSTRACT TRUNCATED AT 250 WORDS)