Current Issue : October-December Volume : 2022 Issue Number : 4 Articles : 5 Articles
Aberrant neurogenesis in the subventricular zone (SVZ) and hippocampus (HIP) contributes to schizophrenia pathogenesis. Haloperidol (HAL) and olanzapine (OLA), commonly prescribed antipsychotics for schizophrenia treatment, affect neurogenesis too. The effect of HAL and OLA on an mHippoE-2 cell line was studied in vitro where we measured the cell number and projection length. In vivo, we studied the gene expression of DCX, Sox2, BDNF, and NeuN in the SVZ and HIP in an MK-801-induced animal schizophrenia model. Cells were incubated with HAL, OLA, and MK-801 for 24, 48, and 72 h. Animals were injected for 6 days with saline or MK801 (0.5 mg/kg), and from the 7th day with either vehicle HAL (1 mg/kg) or OLA (2 mg/kg), for the next 7 days. In vitro, HAL and OLA dose/time-dependently suppressed cells’ proliferation and shortened their projection length. HAL/OLA co-treatment with MK-801 for 24 h reversed HAL’s/OLA’s inhibitory effect. In vivo, HAL and OLA suppressed DCX and NeuN genes’ expression in the HIP and SVZ. MK-801 decreased DCX and NeuN genes’ expression in the HIP and OLA prevented this effect. The data suggest that subchronic HAL/OLA treatment can inhibit DCX and NeuN expression. In an MK-801 schizophrenia model, OLA reversed the MK-801 inhibitory effect on DCX and NeuN and HAL reversed the effect on DCX expression; however, only in the HIP....
The potential effect of intravenous administration of glutamate on the ovarian activity and the LH secretion pattern, considering the anestrous yearling goat as an animal model, were assessed. In late April, yearling goats (n = 20) were randomly assigned to either (1) Glutamate supplemented (GLUT; n = 10, LiveWeight (LW) = 29.6 ± 1.02 kg, Body Condition (BCS) = 3.4 ± 0.2 units; i.v. supplemented with 7 mg GLUT kg−1 LW) or (2) Non-supplemented (CONT; n = 10; LW= 29.2 ± 1.07 kg, BCS = 3.5 ± 0.2 units; i.v. saline). The oats were estrus-synchronized; blood sampling (6 h × 15 min) was carried out for LH quantification. Response variables included pulsatility (PULSE), time to first pulse (TTFP), amplitude (AMPL), nadir (NAD), and area under the curve (AUC) of LH. Ovaries were ultra-sonographically scanned to assess ovulation rate (OR), number of antral follicles (AF), and total ovarian activity (TOA = OR + AF). LH-PULSE was quantified with the Munro algorithm; significant treatment x time interactions were evaluated across time. The variables LWand BCS did not differ (p > 0.05) between the experimental groups. Nevertheless, OR (1.77 vs. 0.87 ± 0.20 units), TOA (4.11 vs. 1.87 ± 0.47 units) and LH-PULSE (5.0 vs. 2.2 pulses 6 h-1) favored (p < 0.05) to the GLUT group. Our results reveal that targeted glutamate supplementation, the main central nervous system neurotransmitter, arose as an interesting strategy to enhance the hypothalamic–hypophyseal–ovarian response considering the anestrous-yearling goat as an animal model, with thought-provoking while promising translational applications....
Background and Objectives: Petechial cerebral hemorrhages can be caused by various factors, such as traumas, cerebral infarctions, and aging, and is related to the disruption of the blood–brain barrier or the cellular damage of blood vessels. However, there is no animal model that recapitulates cerebral petechial hemorrhages. Materials and Methods: Here, we implemented a petechial hemorrhage using a novel technology, i.e., microbubble-assisted focused ultrasound (MB + FUS). Results: This method increases the permeability of the blood–brain barrier by directly applying mechanical force to the vascular endothelial cells through cavitation of the microbubbles. Microbubble-enhanced cavitation has the advantage of controlling the degree and location of petechial hemorrhages. Conclusions: We thus generated a preclinical rat model using noninvasive focal MB + FUS. This method is histologically similar to actual petechial hemorrhages of the brain and allows the achievement of a physiologically resembling petechial hemorrhage. In the future, this method shall be considered as a useful animal model for studying the pathophysiology and treatment of petechial cerebral hemorrhages....
The Renin-Angiotensin System (RAS) is expressed in the central nervous system and has important functions that go beyond blood pressure regulation. Clinical and experimental studies have suggested that alterations in the brain RAS contribute to the development and progression of neurodegenerative diseases. However, there is limited information regarding the involvement of RAS components in Huntington’s disease (HD). Herein, we used the HD murine model, (BACHD), as well as samples from patients with HD to investigate the role of both the classical and alternative axes of RAS in HD pathophysiology. BACHD mice displayed worse motor performance in different behavioral tests alongside a decrease in the levels and activity of the components of the RAS alternative axis ACE2, Ang-(1-7), and Mas receptors in the striatum, prefrontal cortex, and hippocampus. BACHD mice also displayed a significant increase in mRNA expression of the AT1 receptor, a component of the RAS classical arm, in these key brain regions. Moreover, patients with manifest HD presented higher plasma levels of Ang-(1-7). No significant changes were found in the levels of ACE, ACE2, and Ang II. Our findings provided the first evidence that an imbalance in the RAS classical and counter-regulatory arms may play a role in HD pathophysiology....
To combat the COVID-19 pandemic, an assortment of vaccines has been developed. Nucleic acid vaccines have the advantage of rapid production, as they only require a viral antigen sequence and can readily be modified to detected viral mutations. Doggybone™ DNA vaccines targeting the spike protein of SARS-CoV-2 have been generated and compared with a traditionally manufactured, bacterially derived plasmid DNA vaccine that utilizes the same spike sequence. Administered to Syrian hamsters by jet injection at two dose levels, the immunogenicity of both DNA vaccines was compared following two vaccinations. Immunized hamsters were then immunosuppressed and exposed to SARS-CoV-2. Significant differences in body weight were observed during acute infection, and lungs collected at the time of euthanasia had significantly reduced viral RNA, infectious virus, and pathology compared with irrelevant DNA-vaccinated controls. Moreover, immune serum from vaccinated animals was capable of neutralizing SARS-CoV-2 variants of interest and importance in vitro. These data demonstrate the efficacy of a synthetic DNA vaccine approach to protect hamsters from SARS-CoV-2....
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