Activation of glutamine synthetase (GS) as a new strategy for the treatment of major depressive disorder and other GS-related diseases.

Glutamine synthetase (GS) plays a crucial role in the homeostasis of the glutamate-glutamine cycle in the brain. Hypoactive GS causes depressive behaviors. Under chronic stress, GS has no change in expression, but its activity is decreased due to nitration of tyrosine (Tyr).

Neuroprotective Effects of Chaperonin Containing TCP1 Subunit 2 (CCT2) on Motor Neurons Following Oxidative or Ischemic Stress.

Chaperonin containing TCP1 (CCT) is an essential protein that controls proteostasis following spinal cord damage. In particular, CCT2 plays an important role in neuronal death in various neurological disorders; however, few studies have investigated the effects of CCT2 on ischemic damage in the spinal cord. In the present study, we synthesized a cell-permeable Tat-CCT2 fusion protein and observed its effects on HO-induced oxidative damage in NSC34 motoneuron-like cells and in the spinal cord after ischemic injury.

PFKFB3 ameliorates ischemia-induced neuronal damage by reducing reactive oxygen species and inhibiting nuclear translocation of Cdk5.

The enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB) plays an essential role in glycolysis and in the antioxidant pathway associated with glutathione. Therefore, we investigated the effects of PFKFB3 on oxidative and ischemic damage. We synthesized a fusion protein of transactivator of transcription (Tat)-PFKFB3 to facilitate its passage into the intracellular space and examine its effects against oxidative stress induced by hydrogen peroxide (HO) treatment and ischemic damage caused by occlusion of the common carotid arteries for 5 min in gerbils.

Isoflavone-enriched soybean leaves (Glycine max) restore loss of dermal collagen fibers induced by ovariectomy in the Sprague Dawley rats.

Phytoestrogens, such as isoflavones, are known for their capacity to simulate various physiological impacts of estrogen in the human body. Our research evaluated the effects of isoflavone-enriched soybean leaves (IESL) on collagen fiber loss prompted by ovariectomy in Sprague Dawley (SD) rats, thereby simulating menopausal changes in women. IESL, bolstered with an increased concentration of isoflavones through a metabolite farming process, contained a significantly higher amount of isoflavones than regular soybean leaves.

Long-term exposure changes the environmentally relevant bis(2-ethylhexyl) phthalate to be a neuro-hazardous substance disrupting neural homeostasis in emotional and cognitive functions.

Bis(2-ethylhexyl) phthalate (DEHP) is the most used member of the phthalate class of compounds. Extensive use of this plasticizer allows daily exposure to humans via various routes. A positive relationship between DEHP exposure and neurobehavioral disorders is suspected.

Long-Term Hyperglycemia Causes Depressive Behaviors in Mice with Hypoactive Glutamatergic Activity in the Medial Prefrontal Cortex, Which Is Not Reversed by Insulin Treatment.

The etiology of hyperglycemic-induced depressive behaviors is unclear. We hypothesized that long-term hyperglycemia may induce long-lasting disturbances in glutamatergic signaling and neural damages, causing depressive behaviors. To prove our hypothesis, a C57BL/6N mouse model of hyperglycemia was maintained for 4 weeks (equivalent to approximately 3 years in humans), after which insulin treatment was administered for an additional 4 weeks to normalize hyperglycemia-induced changes.

Isoflavone-Enriched Soybean Leaves (Glycine Max) Alleviate Cognitive Impairment Induced by Ovariectomy and Modulate PI3K/Akt Signaling in the Hippocampus of C57BL6 Mice.

(1) Background: The estrogen decline during perimenopause can induce various disorders, including cognitive impairment. Phytoestrogens, such as isoflavones, lignans, and coumestans, have been tried as a popular alternative to avoid the side effects of conventional hormone replacement therapy, but their exact mechanisms and risk are not fully elucidated. In this study, we investigated the effects of isoflavone-enriched soybean leaves (IESLs) on the cognitive impairment induced by ovariectomy in female mice.

Lipocalin-2 Deficiency Reduces Hepatic and Hippocampal Triggering Receptor Expressed on Myeloid Cells-2 Expressions in High-Fat Diet/Streptozotocin-Induced Diabetic Mice.

Background: Lipocalin-2 (LCN2) is an acute-phase protein that has been linked to insulin resistance, diabetes, and neuroinflammatory diseases. Triggering receptor expressed on myeloid cells-2 (TREM2) has been also implicated in microglia-mediated neuroinflammation. However, the potential role of LCN2 on TREM2 in diabetic mouse models is not fully understood.

Phosphodiesterase-5 Inhibitor Attenuates Anxious Phenotypes and Movement Disorder Induced by Mild Ischemic Stroke in Rats.

Objective: Patients with mild ischemic stroke experience various sequela and residual symptoms, such as anxious behavior and deficits in movement. Few approaches have been proved to be effective and safe therapeutic approaches for patients with mild ischemic stroke by acute stroke. Sildenafil (SIL), a phosphodiesterase-5 inhibitor (PDE5i), is a known remedy for neurodegenerative disorders and vascular dementia through its angiogenesis and neurogenesis effects.

Entacapone promotes hippocampal neurogenesis in mice.

Entacapone, a catechol-O-methyltransferase inhibitor, can strengthen the therapeutic effects of levodopa on the treatment of Parkinson's disease. However, few studies are reported on whether entacapone can affect hippocampal neurogenesis in mice. To investigate the effects of entacapone, a modulator of dopamine, on proliferating cells and immature neurons in the mouse hippocampal dentate gyrus, 60 mice (7 weeks old) were randomly divided into a vehicle-treated group and the groups treated with 10, 50, or 200 mg/kg entacapone.

Pyridoxine Deficiency Exacerbates Neuronal Damage after Ischemia by Increasing Oxidative Stress and Reduces Proliferating Cells and Neuroblasts in the Gerbil Hippocampus.

We investigated the effects of pyridoxine deficiency on ischemic neuronal death in the hippocampus of gerbil ( = 5 per group). Serum pyridoxal 5'-phosphate levels were significantly decreased in Pyridoxine-deficient diet (PDD)-fed gerbils, while homocysteine levels were significantly increased in sham- and ischemia-operated gerbils. PDD-fed gerbil showed a reduction in neuronal nuclei (NeuN)-immunoreactive neurons in the medial part of the hippocampal CA1 region three days after.

Tat-Cannabinoid Receptor Interacting Protein Reduces Ischemia-Induced Neuronal Damage and Its Possible Relationship with 14-3-3η.

Cannabinoid receptor-interacting protein 1a (CRIP1a) binds to the -terminal domain of cannabinoid 1 receptor (CB1R) and regulates CB1R activities. In this study, we made Tat-CRIP1a fusion proteins to enhance CRIP1a penetration into neurons and brain and to evaluate the function of CRIP1a in neuroprotection following oxidative stress in HT22 hippocampal cells and transient forebrain ischemia in gerbils. Purified exogenous Tat-CRIP1a was penetrated into HT22 cells in a time and concentration-dependent manner and prevented HO-induced reactive oxygen species formation, DNA fragmentation, and cell damage.

Cuprizone Affects Hypothermia-Induced Neuroprotection and Enhanced Neuroblast Differentiation in the Gerbil Hippocampus after Ischemia.

In the present study, we investigated the effects of cuprizone on cell death, glial activation, and neuronal plasticity induced by hypothermia after ischemia in gerbils. Food was supplemented with cuprizone at 0.2% ad libitum for eight weeks.

Effects of Pyridoxine Deficiency on Hippocampal Function and Its Possible Association with V-Type Proton ATPase Subunit B2 and Heat Shock Cognate Protein 70.

Pyridoxine, one of the vitamin B vitamers, plays a crucial role in amino acid metabolism and synthesis of monoamines as a cofactor. In the present study, we observed the effects of pyridoxine deficiency on novel object recognition memory. In addition, we examined the levels of 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), 3,4-dihydroxyphenethylamine (DA), 3,4-dihydroxyphenylacetic acid, and homovanillic acid and the number of proliferating cells and neuroblasts in the hippocampus.

Altered expression of parvalbumin immunoreactivity in rat main olfactory bulb following pilocarpine-induced status epilepticus.

Epilepsy is a chronic neurological disease characterized by spontaneous recurrent seizures and caused by various factors and mechanisms. Malfunction of the olfactory bulb is frequently observed in patients with epilepsy. However, the morphological changes in the olfactory bulb during epilepsy-induced neuropathology have not been elucidated.

Heat shock protein 70 increases cell proliferation, neuroblast differentiation, and the phosphorylation of CREB in the hippocampus.

In the present study, we investigated the effects of heat shock protein 70 (HSP70) on novel object recognition, cell proliferation, and neuroblast differentiation in the hippocampus. To facilitate penetration into the blood-brain barrier and neuronal plasma membrane, we created a Tat-HSP70 fusion protein. Eight-week-old mice received intraperitoneal injections of vehicle (10% glycerol), control-HSP70, or Tat-HSP70 protein once a day for 21 days.

Differential roles of exogenous protein disulfide isomerase A3 on proliferating cell and neuroblast numbers in the normal and ischemic gerbils.

Introduction: We examined the effects of exogenous protein disulfide isomerase A3 (PDIA3) on hippocampal neurogenesis in gerbils under control and ischemic damage.

Methods: To facilitate the delivery of PDIA3 to the brain, we constructed Tat-PDIA3 protein and administered vehicle (10% glycerol) or Tat-PDIA3 protein once a day for 28 days. On day 24 of vehicle or Tat-PDIA3 treatment, ischemia was transiently induced by occlusion of both common carotid arteries for 5 min.

Phosphoglycerate mutase 1 reduces neuronal damage in the hippocampus following ischemia/reperfusion through the facilitation of energy utilization.

In a previous study, we observed the effect of phosphoglycerate mutase 1 (PGAM1) on proliferating cells and neuroblasts in the subgranular zone of mouse dentate gyrus. In the present study, we examined the roles of PGAM1 in the HT22 hippocampal cell line and in gerbil hippocampus after HO-induced oxidative stress and after ischemia/reperfusion, respectively. Control-PGAM1 and Tat-PGAM1 proteins were synthesized using Tat-1 expression vector since Tat-1 fusion proteins can easily cross the blood-brain barrier and cell membranes.