Antigen-specific age-related memory CD8 T cells induce and track Alzheimer's-like neurodegeneration.

Cerebral (Aβ) plaque and (pTau) tangle deposition are hallmarks of Alzheimer's disease (AD), yet are insufficient to confer complete AD-like neurodegeneration experimentally. Factors acting upstream of Aβ/pTau in AD remain unknown, but their identification could enable earlier diagnosis and more effective treatments. T cell abnormalities are emerging AD hallmarks, and CD8 T cells were recently found to mediate neurodegeneration downstream of tangle deposition in hereditary neurodegeneration models.

CD103 Deficiency Promotes Autism (ASD) and Attention-Deficit Hyperactivity Disorder (ADHD) Behavioral Spectra and Reduces Age-Related Cognitive Decline.

The incidence of autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD), which frequently co-occur, are both rising. The causes of ASD and ADHD remain elusive, even as both appear to involve perturbation of the gut-brain-immune axis. CD103 is an integrin and E-cadherin receptor most prominently expressed on CD8 T cells that reside in gut, brain, and other tissues.

T-Lymphocyte Deficiency Exacerbates Behavioral Deficits in the 6-OHDA Unilateral Lesion Rat Model for Parkinson's Disease.

T-lymphocytes have been previously implicated in protecting dopaminergic neurons in the substantianigra from induced cell death. However, the role of T-cells in neurodegenerative models such as Parkinson's disease (PD) has not been fully elucidated. To examine the role of T-lymphocytes on motor behavior in the 6-hydroxydopamine (6-OHDA) unilateral striatal partial lesion PD rat model, we assessed progression of hemi-parkinsonian lesions in the substantia nigra, induced by 6-OHDA striatal injections, in athymic rats (RNU-/-, T-lymphocyte-deficient) as compared to RNU-/+ rats (phenotypically normal).

Intrinsically de-sialylated CD103(+) CD8 T cells mediate beneficial anti-glioma immune responses.

Background: Cancer vaccines reproducibly cure laboratory animals and reveal encouraging trends in brain tumor (glioma) patients. Identifying parameters governing beneficial vaccine-induced responses may lead to the improvement of glioma immunotherapies. CD103(+) CD8 T cells dominate post-vaccine responses in human glioma patients for unknown reasons, but may be related to recent thymic emigrant (RTE) status.

Prognosis of patients with multifocal glioblastoma: a case-control study.

Object: The prognosis of patients with glioblastoma who present with multifocal disease is not well documented. The objective of this study was to determine whether multifocal disease on initial presentation is associated with worse survival.

Methods: The authors retrospectively reviewed records of 368 patients with newly diagnosed glioblastoma and identified 47 patients with multifocal tumors.

T cells enhance stem-like properties and conditional malignancy in gliomas.

Background: Small populations of highly tumorigenic stem-like cells (cancer stem cells; CSCs) can exist within, and uniquely regenerate cancers including malignant brain tumors (gliomas). Many aspects of glioma CSCs (GSCs), however, have been characterized in non-physiological settings.

Methods: We found gene expression similarity superiorly defined glioma "stemness", and revealed that GSC similarity increased with lower tumor grade.

PDE5 inhibitors enhance tumor permeability and efficacy of chemotherapy in a rat brain tumor model.

The blood-brain tumor barrier (BTB) significantly limits delivery of therapeutic concentrations of chemotherapy to brain tumors. A novel approach to selectively increase drug delivery is pharmacologic modulation of signaling molecules that regulate BTB permeability, such as those in cGMP signaling. Here we show that oral administration of sildenafil (Viagra) and vardenafil (Levitra), inhibitors of cGMP-specific PDE5, selectively increased tumor capillary permeability in 9L gliosarcoma-bearing rats with no significant increase in normal brain capillaries.

Increase in brain tumor permeability in glioma-bearing rats with nitric oxide donors.

Purpose: The blood-brain tumor barrier (BTB) significantly limits the delivery of chemotherapeutics to brain tumors. Nitric oxide (NO) is involved in the regulation of cerebral vascular permeability. We investigated the effects of NO donors, L-arginine and hydroxyurea, on BTB permeability in 9L gliosarcoma-bearing Fischer rats.

In vivo gene delivery to proliferating cells in the striatum generated in response to a 6-hydroxydopamine lesion of the nigro-striatal dopamine pathway.

The degeneration of neurons in the mammalian brain is commonly associated with the division of cells located in the damaged area. The aim of the present study has been to characterise the phenotype of newly born cells in the striatum of adult rats following 6-hydroxydopamine lesion of the nigro-striatal pathway. Newborn cells were identified through labelling with either bromodeoxyuridine or retrovirus encoding green fluorescence protein.

Ngn2 and Nurr1 act in synergy to induce midbrain dopaminergic neurons from expanded neural stem and progenitor cells.

Parkinson's Disease (PD) is a debilitating motor function disorder due primarily to a loss of midbrain dopaminergic neurons and a subsequent reduction in dopaminergic innervation of the striatum. Several attempts have been made to generate dopaminergic neurons from progenitor cell populations in vitro for potential use in cell replacement therapy for PD. However, expanding cells from fetal brain with retained potential for dopaminergic differentiation has proven to be difficult.

Patterns of Jagged1, Jagged2, Delta-like 1 and Delta-like 3 expression during late embryonic and postnatal brain development suggest multiple functional roles in progenitors and differentiated cells.

The Notch-DSL signaling system, consisting of multiple receptors and ligands, inhibits neurogenesis and promotes gliogenesis during embryonic development, but the specific function of the various ligands and receptors at later developmental stages are unknown. Here, we examined the expression pattern of four Delta, Serrate and Lag-2 (DSL) ligands, Jagged1, Jagged2, Delta-like1 (Dl1) and Delta-like 3 (Dl3), in late embryonic and postnatal rat brain by in situ hybridization. In late embryos, Jagged1, Dl1 and Dl3 mRNAs were present in the periventricular germinal epithelia, but this expression diminished during postnatal ages.

Neural progenitor genes. Germinal zone expression and analysis of genetic overlap in stem cell populations.

The identification of the genes regulating neural progenitor cell (NPC) functions is of great importance to developmental neuroscience and neural repair. Previously, we combined genetic subtraction and microarray analysis to identify genes enriched in neural progenitor cultures. Here, we apply a strategy to further stratify the neural progenitor genes.

Extrinsic and intrinsic factors governing cell fate in cortical progenitor cultures.

Central nervous system germinal zones contain stem cells that generate both neurons and glia. In the recent past, these cells have been isolated, maintained in a variety of culture systems and used in vitro for subsequent characterization of molecular mechanisms underlying brain development. Factors that govern cell fate choices of these neural stem cells have not been fully elucidated, but recent studies suggest that age at the time of culture is an important intrinsic mechanism.

The RAS effector RIN1 modulates the formation of aversive memories.

RAS proteins are critical regulators of mitosis and are mutationally activated in many human tumors. RAS signaling is also known to mediate long-term potentiation (LTP) and long-term memory formation in postmitotic neurons, in part through activation of the RAF-MEK-ERK pathway. The RAS effector RIN1 appears to function through competitive inhibition of RAS-RAF binding and also through diversion of RAS signaling to alternate pathways.