Ischemia-Induced Cognitive Impairment Is Improved via Remyelination and Restoration of Synaptic Density in the Hippocampus after Treatment with COG-Up® in a Gerbil Model of Ischemic Stroke

Cerebrovascular disease such as ischemic stroke develops cognitive impairment due to brain tissue damage including neural loss, demyelination and decrease in synaptic density. In the present study, we developed transient ischemia in the forebrain of the gerbil and found cognitive impairment using the Barnes maze test and passive avoidance test for spatial memory and learning memory, respectively. In addition, neuronal loss/death was detected in the Cornu Ammonis 1 (CA1) region of the gerbil hippocampus after the ischemia by cresyl violet histochemistry, immunohistochemistry for neuronal nuclei and histofluorescence with Fluoro-Jade B. Furthermore, in the CA1 region following ischemia, myelin and vesicular synaptic density were significantly decreased using immunohistochemistry for myelin basic protein and vesicular glutamate transporter 1. In the gerbils, treatment with COG-up® (a combined extract of Erigeron annuus (L.) Pers. and Brassica oleracea Var.), which was rich in scutellarin and sinapic acid, after the ischemia, significantly improved ischemia-induced decline in memory function when compared with that shown in gerbils treated with vehicle after the ischemia. In the CA1 region of these gerbils, COG-up® treatment significantly promoted the remyelination visualized using immunohistochemistry myelin basic protein, increased oligodendrocytes visualized using a receptor-interacting protein, and restored the density of glutamatergic synapses visualized using double immunofluorescence for vesicular glutamate transporter 1 and microtubule-associated protein, although COG-up® treatment did not protect pyramidal cells (principal neurons) located in the CA1 region form the ischemic insult. Considering the current findings, a gerbil model of ischemic stroke apparently showed cognitive impairment accompanied by ischemic injury in the hippocampus; also, COG-up® can be employed for improving cognitive decline following ischemia-reperfusion injury in brains.

Layer-Specific Vesicular Glutamate Transporter 1 Immunofluorescence Levels Delineate All Layers of the Human Hippocampus Including the Stratum lucidum

The hippocampal formation consists of the Ammon’s horn (cornu Ammonis with its regions CA1-4), dentate gyrus, subiculum, and the entorhinal cortex. The rough extension of the regions CA1-3 is typically defined based on the density and size of the pyramidal neurons without clear-cut boundaries. Here, we propose the vesicular glutamate transporter 1 (VGLUT1) as a molecular marker for the CA3 region. This is based on its strong labeling of the stratum lucidum (SL) in fluorescently stained human hippocampus sections. VGLUT1 puncta of the intense SL band co-localize with synaptoporin (SPO), a protein enriched in mossy fibers (MFs). Owing to its specific intensity profile throughout all hippocampal layers, VGLUT1 could be implemented as a pendant to Nissl-staining in fluorescent approaches with the additional demarcation of the SL. Furthermore, by high-resolution confocal microscopy, we detected VGLUT2 in the human hippocampus, thus reconciling two previous studies. Finally, by VGLUT1/SPO co-staining, we provide evidence for the existence of infrapyramidal MFs in the human hippocampus and we show that SPO expression is not restricted to MF synapses as demonstrated for rodent tissue.

The Effect of Ceftriaxone in Valproic Acid-Induced Mouse Model of Autism

Purpose: Autism is a multifactorial neurodevelopment disease and it has not been disclosed as a hypoglutamatergic or hyerglutamathergic disease. Ceftriaxone is an antibiotic that increases GLT-1 expression in the brain in chronic use. In our study we aimed to investigate the effects of different doses of ceftriaxone in postnatal period in male mice exposed to valproic acid (VPA) at 12.5th day of pregnancy. Material and Methods: A total of 96 Balb/c male mice were divided into 12 groups (n=8 animals per group). Ceftriaxone (50, 100, 200 mg/kg/day) or saline was given to the male offsprings born from pregnant mice administered VPA and/or saline, between days 47 and 55. Dihydrokainic acid (10 mg/kg), a glutamate transporter-1 (GLT-1) inhibitor, was administered intraperitoneally to evaluate whether GLT-1 mediates the effect of ceftriaxone. Three chamber sociability and social interaction test and the rota rod test were performed in all groups on days 54 and 55. GLT-1 levels in the hippocampus were measured by immunohistochemistry and western blotting. Results: In our study, autism-like behaviors were observed in male offspings that were exposed to VPA in the intrauterine period. Chronic ceftriaxone administration has no curative effect on behavioral impairment seen in autism. Conclusion: Our results show that ceftriaxone did not exert significant therapeutic effect on valproic acid-induced mouse model of autism.

Erratum: Tejeda-Bayron et al. Activation of Glutamate Transporter-1 (GLT-1) Confers Sex-Dependent Neuroprotection in Brain Ischemia. Brain Sci. 2021, 11, 76

The authors wish to make the following corrections to this paper [...]

Age-Related Alterations of Proteins in Albino Wistar Rat Retina

Imbalance of homeostasis causes permanent changes in the body with time. The central nervous system is especially prone to these changes since it possesses limited regenerative capacity. In the retina, neurons are damaged during the aging process, and this eventually leads to deterioration of vision. In our 2-year-long study, we examined genetically closely related rat individuals to disclose the hidden retinal causes of age-associated visual dysfunction. Morphometric analysis showed significant reduction of the retina thickness with aging, particularly that of the inner plexiform layer. To reveal changes between the age groups, we used immunohistochemistry against vesicular glutamate transporter 1 protein for photoreceptor and bipolar cell terminals, Brn3a for ganglion cells, calbindin 28 kDa for horizontal cells, parvalbumin for AII amacrines, protein kinase Cα for rod bipolar cells, tyrosine hydroxylase for dopaminergic cells, glial fibrillary acidic protein for glial cells, and peanut-agglutinin labeling for cones. The most significant decrease was observed in the density of photoreceptor and the ganglion cells in the aging process. By using immunocytochemistry and western blot technique, we observed that calbindin and vesicular glutamate transporter 1 protein staining do not change much with aging; tyrosine hydroxylase, parvalbumin and calretinin showed the highest immunoreactivity during the midlife period. Most interestingly, the level of glial fibrillary acidic protein also changes similarly to the previously named markers. Our results provide further evidence that protein content is modified at least in some cell populations of the rat retina, and the number of retinal cells declined with aging. We conclude that senescence alone may cause structural and functional damage in the retinal tissue.