Changes in peripheral monocyte populations 48-72 hours after subcutaneous denosumab administration in women with osteoporosis.

Objectives: To examine the effect of denosumab administration in the peripheral blood white cell population, to further elucidate a plausible pathophysiological link between denosumab and osteonecrosis of the jaw.

Methods: Thirty women with osteoporosis, after denosumab treatment were included. Peripheral blood samples were obtained prior to and 48-72 hours following denosumab administration.

Application of antibody phage display to identify potential antigenic neural precursor cell proteins.

Background: The discovery of neural precursor cells (NPCs) and the concomitant intensive research in the field offer regenerative medicine novel approaches, enabling it to tackle conditions, such as neurodegenerative diseases. Transplantation of NPCs is nowadays considered a cutting-edge treatment for these conditions and many related clinical trials have been already completed or are still ongoing. However, little is known about the antigenicity of NPCs, with most studies addressing the question whether their antigenicity could lead to rejection of the transplanted cells.

Tauopathy in the young autistic brain: novel biomarker and therapeutic target.

Given our recent discovery of somatic mutations in autism spectrum disorder (ASD)/intellectual disability (ID) genes in postmortem aged Alzheimer's disease brains correlating with increasing tauopathy, it is important to decipher if tauopathy is underlying brain imaging results of atrophy in ASD/ID children. We concentrated on activity-dependent neuroprotective protein (ADNP), a prevalent autism gene. The unique availability of multiple postmortem brain sections of a 7-year-old male, heterozygous for ADNP de novo mutation c.

Reduced expression of L-selectin in T-cells correlates with relative lymphocyte increase in patients with RRMS treated with natalizumab - functional implication towards PML risk.

 Natalizumab (NTZ), a treatment indicated for patients with highly active Relapsing - Remitting Multiple Sclerosis (RRMS), is known to induce increased relative frequency of lymphocytes. Progressive Multifocal Leukoencephalitis (PML) is a rare but serious adverse event related to NTZ. Moreover, reduced L-selectin (CD62L) expression in T-cells in cryopreserved samples of patients with RRMS under NTZ has been proposed as a biomarker of pre-PML state.

Exposure to 3-Nitropropionic Acid Mitochondrial Toxin Induces Tau Pathology in Tangle-Mouse Model and in Wild Type-Mice.

Oxidative stress, particularly of mitochondrial origin, plays an important role in the pathogenesis of neurodegenerative disorders, including Alzheimer's disease (AD) and other tauopathies. Controversies regarding the responses of tau phosphorylation state to various stimuli causing oxidative stress have been reported. Here we investigated the effect of 3-nitropropionic acid (3NP), a mitochondrial toxin which induces oxidative stress, on the tangle-pathology in our previously generated double mutant (E257T/P301S, DM) -Tau-tg mice and in WT-mice.

Spatio-temporal expression profile of NGF and the two-receptor system, TrkA and p75NTR, in experimental autoimmune encephalomyelitis.

Background: Nerve growth factor (NGF) and its receptors, tropomyosin receptor kinase A (TrkA) and pan-neurotrophin receptor p75 (p75NTR), are known to play bidirectional roles between the immune and nervous system. There are only few studies with inconclusive results concerning the expression pattern and role of NGF, TrkA, and p75NTR (NGF system) under the neuroinflammatory conditions in multiple sclerosis (MS) and its mouse model, the experimental autoimmune encephalomyelitis (EAE). The aim of this study is to investigate the temporal expression in different cell types of NGF system in the central nervous system (CNS) during the EAE course.

Exercise intensity-dependent immunomodulatory effects on encephalomyelitis.

Background: Exercise training (ET) has beneficial effects on multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). However, the intensity-dependent effects of ET on the systemic immune system in EAE remain undefined.

Objective: (1) To compare the systemic immune modulatory effects of moderate versus high-intensity ET protocols in protecting against development of EAE; (2) To investigate whether ET affects autoimmunity selectively, or causes general immunosuppression.

Induction of apoptosis in CD4(+) T-cells is linked with optimal treatment response in patients with relapsing-remitting multiple sclerosis treated with Glatiramer acetate.

Background: Induction of T-cell apoptosis constitutes a mechanism of action for Glatiramer Acetate (GA). We investigated whether activation of apoptotic T-cell death may be indicative of optimal treatment response in patients with relapsing-remitting Multiple Sclerosis (RRMS), with respect to radiological activity.

Methods: We studied apoptotic markers on blood T-cells of forty patients with RRMS, 19 patients under GA and 21 patients under interferon-β (IFNβ), by flow cytometry.

The autism/neuroprotection-linked ADNP/NAP regulate the excitatory glutamatergic synapse.

Activity-dependent neuroprotective protein (ADNP), essential for brain formation, was discovered as a leading de novo mutated gene causing the autism-like ADNP syndrome. This syndrome is phenotypically characterized by global developmental delays, intellectual disabilities, speech impediments, and motor dysfunctions. The Adnp haploinsufficient mouse mimics the human ADNP syndrome in terms of synapse density and gene expression patterns, as well as in developmental, motor, and cognitive abilities.

Atypical Auditory Brainstem Response and Protein Expression Aberrations Related to ASD and Hearing Loss in the Adnp Haploinsufficient Mouse Brain.

Autism is a wide spread neurodevelopmental disorder with growing morbidity rates, affecting more boys than girls worldwide. Activity-dependent neuroprotective protein (ADNP) was recently recognized as a leading gene accounted for 0.17% of autism spectrum disorder (ASD) cases globally.

Cyclization of PLP peptide reduces its encephalitogenic potential in experimental autoimmune encephalomyelitis.

We report the novel synthesis of cyclic PLP (cPLP) and its application in SJL/J mice to study its encephalitogenic effects. Our results indicate that the cPLP analog is minimally encephalitogenic when administered to induce experimental autoimmune encephalomyelitis (low disease burden, minimal inflammatory, demyelinating and axonopathic pathology compared to its linear counterpart). Proliferation assays confirmed the low stimulatory potential of the cPLP compared to linPLP (2.

Beneficial effects of environmental enrichment on behavior, stress reactivity and synaptophysin/BDNF expression in hippocampus following early life stress.

Exposure to environmental enrichment can beneficially influence the behavior and enhance synaptic plasticity. The aim of the present study was to investigate the mediated effects of environmental enrichment on postnatal stress-associated impact with regard to behavior, stress reactivity as well as synaptic plasticity changes in the dorsal hippocampus. Wistar rat pups were submitted to a 3 h maternal separation (MS) protocol during postnatal days 1-21, while another group was left undisturbed.

Humoral response in experimental autoimmune encephalomyelitis targets neural precursor cells in the central nervous system of naive rodents.

Background: Neural precursor cells (NPCs) located in the subventricular zone (SVZ), a well-defined NPC niche, play a crucial role in central nervous system (CNS) homeostasis. Moreover, NPCs are involved in the endogenous reparative process both in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). However, the possibility that NPCs may be vulnerable to immune-related components may not be ruled out.

Exercise training attenuates experimental autoimmune encephalomyelitis by peripheral immunomodulation rather than direct neuroprotection.

Background: Conflicting results exist on the effects of exercise training (ET) on Experimental Autoimmune Encephalomyelitis (EAE), nor is it known how exercise impacts on disease progression.

Objective: We examined whether ET ameliorates the development of EAE by modulating the systemic immune system or exerting direct neuroprotective effects on the CNS.

Methods: Healthy mice were subjected to 6weeks of motorized treadmill running.

Long-term effects of enriched environment following neonatal hypoxia-ischemia on behavior, BDNF and synaptophysin levels in rat hippocampus: Effect of combined treatment with G-CSF.

Increasing evidence shows that exposure to an enriched environment (EE) is neuroprotective in adult and neonatal animal models of brain ischemia. However, the mechanisms underlying this effect remain unclear. The aim of the current study was to investigate whether post-weaning EE would be effective in preventing functional deficits and brain damage by affecting markers of synaptic plasticity in a neonatal rat model of hypoxia-ischemia (HI).

A case of CD30+ ALK1- anaplastic large cell lymphoma resembling acute disseminated encephalomyelitis.

Central nervous system involvement is an uncommon complication of systemic non-Hodgkin lymphomas. The majority of these cases concern B-cell lymphomas. We report a case of systemic T-cell anaplastic large cell lymphoma CD30+ ALK- with CNS involvement at the time of diagnosis and unusual MRI characteristics resembling acute disseminated encephalomyelitis.

Increased CD14+ and decreased CD14- populations of monocytes 48 h after zolendronic acid infusion in breast cancer patients.

Unlabelled: It has been proposed that bisphosphonates cause osteonecrosis of the jaws through impairment of the monocyte population function and proliferation. Such changes have been confirmed in jaw tissues, ex vivo. In this clinical study, we report for the first time a similar pattern of changes in peripheral blood monocytes.

Nogo receptor complex expression dynamics in the inflammatory foci of central nervous system experimental autoimmune demyelination.

Background: Nogo-A and its putative receptor NgR are considered to be among the inhibitors of axonal regeneration in the CNS. However, few studies so far have addressed the issue of local NgR complex multilateral localization within inflammation in an MS mouse model of autoimmune demyelination.

Methods: Chronic experimental autoimmune encephalomyelitis (EAE) was induced in C57BL/6 mice.

Validation of the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) in Greek population with multiple sclerosis.

Background: Cognitive impairment is experienced by about 50% of patients with Multiple Sclerosis (MS) worldwide and affects their employment, disease management and quality of life in general. The Brief International Cognitive assessment for MS (BICAMS) is a brief, practical and potentially universal battery for cognitive impairment in MS patients. It consists of three tests: the Symbol Digit Modalities Test (SDMT), the California Verbal Learning Test-2 (CVLT-2) and the Brief Visuospatial Memory Test-Revised (BVMT-R).

The Impact of Methylprednisolone Pulses during Relapses of Multiple Sclerosis on the Kinetics of Anti-Interferon-Beta Antibodies.

Background/aims: We assessed the, hitherto unknown, impact of intravenous methylprednisolone (ivMP) pulses during relapses of multiple sclerosis (MS) on the kinetics of anti-interferon-beta neutralizing antibodies (Nabs) and binding antibodies (Babs).

Methods: Babs (ELISA) and Nabs (antiviral cytopathic effect assay) titers were evaluated before, immediately after and at 1 month following ivMP in 60 MS patients.

Results: ivMP reduces Nabs and Babs titers for at least 1 month.

Sexual divergence in microtubule function: the novel intranasal microtubule targeting SKIP normalizes axonal transport and enhances memory.

Activity-dependent neuroprotective protein (ADNP), essential for brain formation, is a frequent autism spectrum disorder (ASD)-mutated gene. ADNP associates with microtubule end-binding proteins (EBs) through its SxIP motif, to regulate dendritic spine formation and brain plasticity. Here, we reveal SKIP, a novel four-amino-acid peptide representing an EB-binding site, as a replacement therapy in an outbred Adnp-deficient mouse model.

Immunophenotype of mouse cerebral hemispheres-derived neural precursor cells.

Postnatally isolated neural precursor cells (piNPCs) from mouse cerebral tissue have been studied in cell-based therapeutic approaches for Experimental Autoimmune Encephalomyelitis (EAE). Transplantation experiments in EAE rodents revealed that piNPCs manage to integrate into the host tissue and ameliorate clinical symptoms. When cultured in vitro, mouse cerebral piNPCs form neurospheres consisting of immature cells positive for polysialylated neural adhesion molecule (PSA-NCAM) that differentiate mainly towards glial cells, but also neurons.