cellular apoptosis mitochondrial function and confers resistance to The arginine metabolite agmatine protects

is dedicated to innovative approaches to the study of cell and molecular physiology. It is published 12 times AJP -Cell Physiolog

The septohippocampal cholinergic system and spatial working memory in the Morris water maze.

The objective of the present study was to determine whether a systematic optimization of Morris water maze (mwm) testing parameters could reveal a significant role of the septohippocampal cholinergic system in spatial working memory. Young adult rats were lesioned using 192 IgG-saporin infused bilaterally into the medial septum. Lesions were near complete as measured by choline acetyltransferase (ChAT) activity and immunohistochemistry. Behavioral testing was performed in three phases. In the first, lesioned and unlesioned rats were trained in the mwm focusing on working memory, which was tested using novel platform locations daily. In the second phase, the optimal locations were retested with increasing intertrial intervals (ITI). In the third phase, intracerebroventricular infusions of nerve growth factor (NGF) were employed to enhance cholinergic activity of the unlesioned rats and potentially further separate group performance. Neither the standard or increased ITI resulted in a consistent significant difference in spatial working memory between groups. In addition, NGF treatment also failed to induce a significant difference in behavioral performance. In conclusion, impairments in working memory as assessed by the mwm could not be revealed despite a greater than 90% loss of hippocampal ChAT and the use of optimal testing parameters and NGF treatment

Nerve growth factor promotes survival of new neurons in the adult hippocampus.

xogenously provided NGF enhances cognitive performance in impaired rodents and humans and is currently a promising compound for the treatment of dementia. To investigate whether NGF-dependent cognitive improvement may be due in part to increased hippocampal neurogenesis, adult and aged male rats were treated with NGF or vehicle intracerebroventricularly for 6 or 20 days followed by evaluation of cholinergic parameters and hippocampal neurogenesis. We show that NGF increases hippocampal cholinergic activity as rapidly as 3 days after initiation of treatment. NGF treatment for 6 days did not affect proliferation of progenitor cells in the dentate gyrus granule cell layer (GCL). However, continuous NGF infusion enhanced survival of new neurons in the GCL of young adult, but not aged rats. Taken together, these findings suggest that NGF, likely mediated through increased cholinergic tone, promotes neurogenesis in the adult hippocampus, which may relate to the nootropic action of NGF

Intracerebroventricular Administration of Nerve Growth Factor Induces Gliogenesis in Sensory Ganglia, Dorsal Root, and within the Dorsal Root Entry Zone

Previous studies indicated that intracerebroventricular administration of nerve growth factor (NGF) leads to massive Schwann cell hyperplasia surrounding the medulla oblongata and spinal cord. This study was designed to characterize the proliferation of peripheral glial cells, that is, Schwann and satellite cells, in the trigeminal ganglia and dorsal root ganglia (DRG) of adult rats during two weeks of NGF infusion using bromodeoxyuridine (BrdU) to label dividing cells. The trigeminal ganglia as well as the cervical and lumbar DRG were analyzed. Along the entire neuraxis a small number of dividing cells were observed within these regions under physiological condition. NGF infusion has dramatically increased the generation of new cells in the neuronal soma and axonal compartments of sensory ganglia and along the dorsal root and the dorsal root entry zone. Quantification of BrdU positive cells within sensory ganglia revealed a 2.3- to 3-fold increase in glial cells compared to controls with a similar response to NGF for the different peripheral ganglia examined. Immunofluorescent labeling with S100β revealed that Schwann and satellite cells underwent mitosis after NGF administration. These data indicate that intracerebroventricular NGF infusion significantly induces gliogenesis in trigeminal ganglia and the spinal sensory ganglia and along the dorsal root entry zone as well as the dorsal root

Unusual anatomic variant of the axillary nerve challenging the deltopectoral approach to the shoulder: a case report

Abstract Background The deltopectoral approach is a well-described surgical approach to the proximal humerus and glenohumeral joint. One of the structures at risk during this approach is the axillary nerve. Typically, the axillary nerve arises off the posterior cord of the brachial plexus and courses lateral to the proximal humerus and inferior to the glenohumeral joint, exiting the axilla through the quadrangular space. We describe a case of an aberrant axillary nerve, coursing anteriorly across the glenohumeral joint within the deltopectoral groove encountered during a reverse total shoulder arthroplasty. Case presentation A 73-year-old female presented complaining of atraumatic progressive right shoulder pain of several months duration. Clinical and radiographic findings were consistent with advanced rotator cuff arthropathy. After failing appropriate non-operative treatment, the patient elected to undergo reverse total shoulder arthroplasty. During the deltopectoral approach to the glenohumeral joint, the axillary nerve was found to be coursing deep to the cephalic vein within the deltopectoral interval. The nerve was isolated and protected, and the glenohumeral joint was accessed via a small window in the anterior deltoid muscle. The remainder of the procedure was performed without complication. The patient was found to be healing well and with normal axillary nerve function at 4-month follow-up. Conclusions Neurologic lesions are well-documented complications of reverse total shoulder arthroplasty. The integrity of the axillary nerve is of particular importance to reverse total shoulder arthroplasty as it innervates the deltoid and post-operative function of the extremity is dependent upon a functioning deltoid muscle. Extreme care must be taken to avoid insult to the axillary nerve and any aberrant paths it may course around the glenohumeral joint

Activation of the Interferon Pathway in Trophoblast Cells Productively Infected with SARS-CoV-2.

SARS-CoV-2 infection during pregnancy has been associated with poor maternal and neonatal outcomes and placental defects. The placenta, which acts as a physical and immunological barrier at the maternal-fetal interface, is not established until the end of the first trimester. Therefore, localized viral infection of the trophoblast compartment early in gestation could trigger an inflammatory response resulting in altered placental function and consequent suboptimal conditions for fetal growth and development. In this study, we investigated the effect of SARS-CoV-2 infection in early gestation placentae using placenta-derived human trophoblast stem cells (TSCs), a novel in vitro model, and their extravillous trophoblast (EVT) and syncytiotrophoblast (STB) derivatives. SARS-CoV-2 was able to productively replicate in TSC-derived STB and EVT, but not undifferentiated TSCs, which is consistent with the expression of SARS-CoV-2 entry host factors, ACE2 (angiotensin-converting enzyme 2) and TMPRSS2 (transmembrane cellular serine protease) in these cells. In addition, both TSC-derived EVT and STB infected with SARS-CoV-2 elicited an interferon-mediated innate immune response. Combined, these results suggest that placenta-derived TSCs are a robust in vitro model to investigate the effect of SARS-CoV-2 infection in the trophoblast compartment of the early placenta and that SARS-CoV-2 infection in early gestation activates the innate immune response and inflammation pathways. Therefore, placental development could be adversely affected by early SARS-CoV-2 infection by directly infecting the developing differentiated trophoblast compartment, posing a higher risk for poor pregnancy outcomes

Rescue of Alzheimer’s disease phenotype in a mouse model by transplantation of wild-type hematopoietic stem and progenitor cells

Alzheimer's disease (AD) is the most prevalent cause of dementia; microglia have been implicated in AD pathogenesis, but their role is still matter of debate. Our study showed that single systemic wild-type (WT) hematopoietic stem and progenitor cell (HSPC) transplantation rescued the AD phenotype in 5xFAD mice and that transplantation may prevent microglia activation. Indeed, complete prevention of memory loss and neurocognitive impairment and decrease of β-amyloid plaques in the hippocampus and cortex were observed in the WT HSPC-transplanted 5xFAD mice compared with untreated 5xFAD mice and with mice transplanted with 5xFAD HSPCs. Neuroinflammation was also significantly reduced. Transcriptomic analysis revealed a significant decrease in gene expression related to "disease-associated microglia" in the cortex and "neurodegeneration-associated endothelial cells" in the hippocampus of the WT HSPC-transplanted 5xFAD mice compared with diseased controls. This work shows that HSPC transplant has the potential to prevent AD-associated complications and represents a promising therapeutic avenue for this disease