Hippocampus Cerebral Cortex Research Articles

Prophylactic Subacute Administration of Zinc Increases CCL2, CCR2, FGF2, and IGF-1 Expression and Prevents the Long-Term Memory Loss in a Rat Model of Cerebral Hypoxia-Ischemia.

Prophylactic subacute administration of zinc decreases lipoperoxidation and cell death following a transient cerebral hypoxia-ischemia, thus suggesting neuroprotective and preconditioning effects. Chemokines and growth factors are also involved in the neuroprotective effect in hypoxia-ischemia. We explored whether zinc prevents the cerebral cortex-hippocampus injury through regulation of CCL2, CCR2, FGF2, and IGF-1 expression following a 10 min of common carotid artery occlusion (CCAO). Male rats were grouped as follows: (1) Zn96h, rats injected with ZnCl2 (one dose every 24 h during four days); (2) Zn96h + CCAO, rats treated with ZnCl2 before CCAO; (3) CCAO, rats with CCAO only; (4) Sham group, rats with mock CCAO; and (5) untreated rats. The cerebral cortex-hippocampus was dissected at different times before and after CCAO. CCL2/CCR2, FGF2, and IGF-1 expression was assessed by RT-PCR and ELISA. Learning in Morris Water Maze was achieved by daily training during 5 days. Long-term memory was evaluated on day 7 after learning. Subacute administration of zinc increased expression of CCL2, CCR2, FGF2, and IGF-1 in the early and late phases of postreperfusion and prevented the CCAO-induced memory loss in the rat. These results might be explained by the induction of neural plasticity because of the expression of CCL2 and growth factors.

The increase in Zinc levels and upregulation of Zinc transporters are mediated by nitric oxide in the cerebral cortex after transient ischemia in the rat

The transient occlusion of cerebral arteries causes an increase in zinc levels in the brain, which is associated with a production of nitric oxide (NO). The types of zinc transporters (ZnT) involved in zinc homeostasis in the cerebral cortex after hypoxia–ischemia are not completely known. We studied the effect of the transient occlusion (10 min) of the common carotid artery (CCA) on NO-induced zinc levels, ZnT mRNA expression, and cell-death markers in the cerebral cortex–hippocampus of the rat. Nitrites, zinc, and lipoperoxidation were quantified by colorimetric methods, ZnT expression was determined by RT-PCR, caspase-3 by ELISA and immunohistochemistry, and histopathological alterations by H&E staining. After restoration of the blood flow, the basal levels of NO and zinc increased in a biphasic manner over time, but the peaks of NO levels appeared earlier (2 h and 24 h) than those of zinc (6 h and 36 h). Upregulation of ZnT1, ZnT2, and ZnT4 mRNAs was determined after 8-h postreperfusion, but ZnT3 RNA levels were unaffected. Lipoperoxidation and caspase-3 levels were also increased, and necrosis and apoptosis were present at 24 h postreperfusion. All the effects determined were prevented by l-nitro-arginine methyl ester injected 1 h before the occlusion of the CCA. Our results suggest that the upregulation of ZnT1, ZnT2, and ZnT4 was to decrease the cytosolic zinc levels caused by NO after transient occlusion of the CCA, although this was unable to lead to physiological levels of zinc and to prevent cell damage in the cerebral cortex–hippocampus of the rat.

Tissue specific increase of the catalytic subunits of the 26S proteasome by indirect antioxidant dithiolethione in mice: Enhanced activity for degradation of abnormal protein

Decreases in the 26S proteasome are related to the toxicities of abnormal protein aggregates and may contribute to pathogenesis of degenerative diseases. Therefore, maintenance of proteasome function can be a novel strategy to protect cells against abnormal protein-mediated toxicity. In the present study, we have demonstrated the tissue specific increase of the catalytic subunits of the proteasome in mice following oral administration of 3 H-1,2-dithiole-3-thione (D3T, 0.5 mmol/kg), which functions as a cancer preventive agent in animal and human studies. Expression of the 20S catalytic core subunits PSMB5, PSMB6, and PSMB7 were increased in liver, lung, small intestine, and colon of mice at 24 h after D3T treatment. Elevated expression of proteasome catalytic subunits led to increases in proteasomal peptidase activities in these tissues. Oral administration of D3T also exerted a pharmacodynamic action in some brain regions of these mice and proteasomal peptidase activities were significantly elevated in the cerebral cortex–hippocampus. Moreover, tissue extracts from D3T-treated mice and cell lysates obtained from D3T-incubated murine neuroblastoma cells exhibited the enhanced capacity to degrade mutant human SOD1G93A protein. These results indicate that the catalytic subunits of the 26S proteasome are inducible in multiple tissues of mouse including brain by exogenous chemical treatment. Increased proteasome expression by inducers may have a role in protection/attenuation of protein aggregate-mediated disorders.

Chapter 2 Presynaptic modulation of glutamate release

Publisher Summary Presynaptic receptors could modulate the probability of vesicle release in response to an invading action potential by a number of mechanisms—firstly by altering the kinetics of K+ or Na+ channels and influencing the waveform of the depolarization, secondly by activating or inhibiting the release-coupled Ca2+ channel and directly controlling the access of Ca2+ to the exocytotic trigger, or thirdly by acting at an intracellular locus to control some aspect of the exocytotic/endocytic cycle. Synaptosomes have proved a valuable preparation for the investigation of these presynaptic regulatory pathways. Glutamate exocytosis greatly outweighs the release of other transmitters in preparations from cerebral cortex—hippocampus or cerebellum—and is the simplest preparation, which retains all the pathways for the synthesis, storage, release, and reuptake of transmitter glutamate, together with a range of presynaptic receptors capable of modulating the release of the transmitter. Agonists and antagonists targeting the presynaptic glutamatergic terminal greatly influence the in vitro and in vivo release of the transmitter.

Regional distribution of Neuropeptide K and other tachykinins (Neurokinin A, Neurokinin B and substance P) in rat central nervous system

Neurokinin A and A (NKA and NKB) and neuropeptide K (NPK) were recently isolated from porcine spinal cord and brain, and together with substance P (SP) considerably extend the list of tachykinin-like peptides present in the mammalian nervous system. In order to investigate the distribution of tachykinins in the central nervous system (CNS) we have recently developed sensitive radioimmunoassays (RIA) for both SP and NKA. As NKB and NPK cross-react in the RIA for NKA we were able to determined the content of NKA, NKB and NPK after separation of rat CNS extracts by reverse-phase high-performance liquid chromatography (HPLC). Comparison of different extraction methods suggested that 0.1 M hydrochloric acid gave the best extraction and recovery of NKA-like immunoreactivity from rat brain. Characterization of these tachykinins using HPLC and gel-filtration columns revealed that C 18 columns did not adequately separate NPK from NKB under the conditions used by previous authors. Thus ‘NKB’ content reported previously on the basis of HPLC separation would correspond to the sum of both NPK and NKB content. In the present study, therefore, we introduced modified elution conditions to resolve NPK from NKB and determined the regional distributions of these tachykinins in the rat CNS. SP was the most abundant tachykinin in every region studied. After SP, the NKA concentration was highest and NKB concentration was lowest in all regions except for the cortex and hippocampus where the NPK concentration was highest. The molar ratio of these peptides seemed to be relatively constant in the 3 regional groups (striatum-substantia nigra, cerebral cortex-hippocampus, dorsal root ganglia-dorsal and ventral horns of spinal cord) and suggest that regional specific translation or processing may exist.