CHI3L1
Chitinase-3-like protein 1 precursor (39 kDa synovial protein) (Cartilage glycoprotein 39) (CGP-39) (GP-39) (hCGP-39) (YKL-40)
Publications[править]
Alzheimer's disease (AD) is one of the most common forms of dementia with still unknown pathogenesis. Several cytokines and chemokines are involved in the pathogenesis of AD. Among the chemokines, the CXCR4/CXCL12 complex has been shown to play an important role in the pathogenetic development of AD. We investigated the expression levels of CXCR4 / CXCL12 in fifteen brain regions of healthy non-demented subjects (NDHC) (2139 sample) and AD patients (1170 sample) stratified according to sex and age. Furthermore, we correlated their expressions with the Neurogranin (NRGN) and CHI3L1 levels, two inflamm-aging markers. We highlighted that CXCR4 gene expression levels were age-correlated in the brain of NDHC subjects and that AD nullified this correlation. A similar trend, but diametrically opposite was observed for CXCL12. Its expression was decreased during the aging in both sexes, and in the brains of AD patients, it underwent an inversion of the trend, only and exclusively in females. Brains of AD patients expressed high CXCR4 and CHI3L1, and low CXCL12 and Neurogranin levels compared to NDHC subjects. Both CXCR4 and CXCL12 correlated significantly with CHI3L1 and Neurogranin expression levels, regardless of disease. Furthermore, we showed a selective modulation of CXCL12 and CXCR4 only in specific brain regions. Taken together our results demonstrate that CXCL12 and CXCR4 are linked to Neurogranin and CHI3L1 expression levels and the relationship between postsynaptic damage and microglial activation in AD could be shown using all these genes. Further confirmations are needed to demonstrate the close link between these genes.
Keywords
- Aging
- Alzheimer’s disease
- Bioinformatics
- CHI3L1
- Chitinase
- NRGN
Several genetic sexual dimorphisms have been identified in animal and human brains, which may form a neural basis for sex-specific predisposition to neurological diseases. In the last years, clinical studies have observed that Alzheimer's disease (AD) disproportionately affects women compared with men. Chitinase-3-Like 1 protein (CHI3L1) has been frequently investigated in body fluids as a surrogate marker of neuroinflammation in AD and other neurological disorders. Nevertheless, the sex-related differences in CHI3L1 expression in the human brain has not yet been investigated. Here we aimed to evaluate the specificity of increase of CHI3L1 in five brain regions (cerebellum, dorsolateral prefrontal cortex, prefrontal cortex, hippocampus, and visual cortex) of male and female controls during normal aging, as well as in AD patients. We selected ten microarray datasets from NCBI, representing normal aging (n = 1290) and AD (n = 992), and stratified the brain specimens according to age, gender and brain region. The expression levels of CHI3L1 were correlated with age and gender. Female control brain specimens showed higher CHI3L1 expression than male brains. The expression differences between men and women were most obvious in older subjects. The expression analysis of CHI3L1 in the different brain regions of AD subjects also showed sex differences; females with AD had greater expression in the cerebellum than males. Notably, sex-associated CHI3L1 expression differences in hippocampus disappeared in AD. These findings demonstrate that the expression of CHI3L1 in the brains of cognitively unimpaired subjects and AD patients is closely linked to age and sex, which was most obvious in the cerebellum. Further studies are needed to confirm our results.
MeSH Terms
- Adult
- Age Factors
- Aged
- Aged, 80 and over
- Aging
- Alzheimer Disease
- Amyloid beta-Peptides
- Biomarkers
- Brain
- Cerebellum
- Chitinase-3-Like Protein 1
- Disease Susceptibility
- Female
- Gene Expression Profiling
- Hippocampus
- Humans
- Male
- Middle Aged
- Nervous System Diseases
- Prefrontal Cortex
- Sex Characteristics
- Sex Factors
- Transcriptome
- Visual Cortex
Keywords
- Alzheimer’s disease
- CHI3L1
- Chitinase
- Sex
- YKL40
CHI3L1 (YKL-40) is up-regulated in a variety of inflammatory conditions and cancers. We have previously reported elevated CHI3L1 concentration in the cerebrospinal fluid (CSF) of human and non-human primates with lentiviral encephalitis and using immunohistochemistry showed that CHI3L1 was associated with astrocytes. In the current study CHI3L1 transcription and expression were evaluated in a variety of acute and chronic human neurological diseases. ELISA revealed significant elevation of CHI3L1 in the CSF of multiple sclerosis (MS) patients as well as mild elevation with aging. In situ hybridization (ISH) showed CHI3L1 transcription mostly associated with reactive astrocytes, that was more pronounced in inflammatory conditions like lentiviral encephalitis and MS. Comparison of CHI3L1 expression in different stages of brain infarction showed that YKL40 was abundantly expressed in astrocytes during acute phases and diminished to low levels in chronic infarcts. Taken together, these findings demonstrate that CHI3L1 is induced in astrocytes in a variety of neurological diseases but that it is most abundantly associated with astrocytes in regions of inflammatory cells.
MeSH Terms
- Adipokines
- Adult
- Aged
- Aged, 80 and over
- Aging
- Alzheimer Disease
- Amyotrophic Lateral Sclerosis
- Animals
- Astrocytes
- Chitinase-3-Like Protein 1
- Chronic Disease
- Female
- Glycoproteins
- Humans
- Lectins
- Macaca nemestrina
- Male
- Middle Aged
- Multiple Sclerosis
- Nervous System Diseases
- Stroke