Early postnatal chronic inflammation produces long-term changes in pain behavior and N-methyl-D-aspartate receptor subtype gene expression in the central nervous system of adult mice

AbstractDirect delivery of therapeutic enzymes to the Central Nervous System requires stringent formulation design. Not only should the formulation design consider the delicate balance of existing ions, proteins, and osmolality in the cerebrospinal fluid, it must also provide long term efficacy and stability for the enzyme. One fundamental approach to this predicament is designing formulations with no buffering species. In this study, we report a high concentration, saline-based formulation for a human sulfatase for its delivery into the intrathecal space. A high concentration formulation (≤ 40 mg/mL) was developed through a series of systematic studies that demonstrated the feasibility of a self-buffered formulation for this molecule. The self-buffering capacity phenomenon was found to be a product of both the protein itself and potentially the residual phosphates associated with the protein. To date, the self-buffered formulation for this molecule has been stable for up to 4 years when stored at 5 ± 3 °C, with no changes either in the pH values or other quality attributes of the molecule. The high concentration self-buffered protein formulation was also observed to be stable when exposed to multiple freeze–thaw cycles and was robust during in-use and agitation studies.

Download Full-text

A novel gene signature based on five immune checkpoint genes predicts the survival of glioma

Chinese Neurosurgical Journal ◽

10.1186/s41016-020-00220-2 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Wei Zhang ◽

You Zhai ◽

Guanzhang Li ◽

Tao Jiang

Keyword(s):

Gene Expression ◽

Central Nervous System ◽

Immune Response ◽

Nervous System ◽

Cox Regression ◽

Gene Signature ◽

Immune Checkpoints ◽

The Novel ◽

The Central Nervous System ◽

Checkpoint Genes

Abstract Background Glioma is the most common and fatal type of nerve neoplasm in the central nervous system. Several biomarkers have been considered for prognosis prediction, which is not accurate enough. We aimed to carry out a gene signature related to the expression of immune checkpoints which was enough for its performance in prediction. Methods Gene expression of immune checkpoints in TGGA database was filtrated. The 5 selected genes underwent verification by COX and Lasso-COX regression. Next, the selected genes were included to build a novel signature for further analysis. Results Patients were sub-grouped into high and low risk according to the novel signature. Immune response, clinicopathologic characters, and survival showed significant differences between those 2 groups. Terms including “naive,” “effector,” and “IL-4” were screened out by GSEA. The results showed strong relevance between the signature and immune response. Conclusions We constructed a gene signature with 5 immune checkpoints. The signature predicted survival effectively. The novel signature performed more functional than previous biomarkers.

Download Full-text

GAP-43 gene expression during postnatal development in the central nervous system of macaque monkey

Neuroscience Research Supplements ◽

10.1016/0921-8696(94)92605-0 ◽

1994 ◽

Vol 19 ◽

pp. S121 ◽

Cited By ~ 2

Author(s):

Takao Oishi ◽

Keiji Matsuda ◽

Noriyuki Higo ◽

Yumiko Umino ◽

Motoharu Hayashi

Keyword(s):

Gene Expression ◽

Central Nervous System ◽

Nervous System ◽

Postnatal Development ◽

Macaque Monkey ◽

The Central Nervous System

Download Full-text

Cloning of glucocorticoid receptor and mineralocorticoid receptor cDNA and gene expression in the central nervous system of the tree shrew (Tupaia belangeri)

Molecular Brain Research ◽

10.1016/s0169-328x(98)00004-7 ◽

1998 ◽

Vol 55 (2) ◽

pp. 243-253 ◽

Cited By ~ 39

Author(s):

Ute Meyer ◽

Mogens Kruhøffer ◽

Gabriele Flügge ◽

Eberhard Fuchs

Keyword(s):

Gene Expression ◽

Central Nervous System ◽

Nervous System ◽

Glucocorticoid Receptor ◽

Mineralocorticoid Receptor ◽

Tree Shrew ◽

Tupaia Belangeri ◽

The Central Nervous System ◽

Receptor Cdna

Download Full-text

Regulation of Cholesterol Homeostasis by the Liver X Receptors in the Central Nervous System

Molecular Endocrinology ◽

10.1210/mend.16.6.0835 ◽

2002 ◽

Vol 16 (6) ◽

pp. 1378-1385 ◽

Cited By ~ 78

Author(s):

Karl D. Whitney ◽

Michael A. Watson ◽

Jon L. Collins ◽

William G. Benson ◽

Tammy M. Stone ◽

...

Keyword(s):

Gene Expression ◽

Central Nervous System ◽

Nervous System ◽

Cholesterol Efflux ◽

Target Genes ◽

Cholesterol Homeostasis ◽

Neuronal Cultures ◽

Primary Neuronal Cultures ◽

The Central Nervous System ◽

Lxr Agonists

Abstract The nuclear oxysterol receptors liver X receptor-α [LXRα (NR1H3)] and LXRβ (NR1H2) coordinately regulate genes involved in cholesterol homeostasis. Although both LXR subtypes are expressed in the brain, their roles in this tissue remain largely unexplored. In this report, we show that LXR agonists have marked effects on gene expression in murine brain tissue both in vitro and in vivo. In primary astrocyte cultures, LXR agonists regulated several established LXR target genes, including ATP binding cassette transporter A1, and enhanced cholesterol efflux. In contrast, little or no effect on gene expression or cholesterol efflux was detected in primary neuronal cultures. Treatment of mice with a selective LXR agonist resulted in the induction of several LXR target genes related to cholesterol homeostasis in the cerebellum and hippocampus. These data provide the first evidence that the LXRs regulate cholesterol homeostasis in the central nervous system. Because dysregulation of cholesterol balance is implicated in central nervous system diseases such as Alzheimer’s and Niemann-Pick disease, pharmacological manipulation of the LXRs may prove beneficial in the treatment of these disorders.

Download Full-text