GFAP expression and social deficits in transgenic mice overexpressing human sAPPα
Antoinette R. Bailey,Huayan Hou,Min Song,Demian Obregon,Samantha M. Portis,Steven W. Barger,Doug Shytle,Saundra Stock,Takashi Mori,Paul G. Sanberg,Tanya K. Murphy,Jun Tan +11 more
Reads0
Chats0
TLDR
The results suggest that elevations in brain sAPPα levels are observed in subsets of individuals with autism and TgsAPPα mice display signs suggestive of gliosis and behavioral impairment.Abstract:
Autistic individuals display impaired social interactions and language, and restricted, stereotyped behaviors. Elevated levels of secreted amyloid precursor protein-alpha (sAPPα), the product of α-secretase cleavage of APP, are found in the plasma of some individuals with autism. The sAPPα protein is neurotrophic and neuroprotective and recently showed a correlation to glial differentiation in human neural stem cells (NSCs) via the IL-6 pathway. Considering evidence of gliosis in postmortem autistic brains, we hypothesized that subsets of patients with autism would exhibit elevations in CNS sAPPα and mice generated to mimic this observation would display markers suggestive of gliosis and autism-like behavior. Elevations in sAPPα levels were observed in brains of autistic patients compared to controls. Transgenic mice engineered to overexpress human sAPPα (TgsAPPα mice) displayed hypoactivity, impaired sociability, increased brain glial fibrillary acidic protein (GFAP) expression, and altered Notch1 and IL-6 levels. NSCs isolated from TgsAPPα mice, and those derived from wild-type mice treated with sAPPα, displayed suppressed β-tubulin III and elevated GFAP expression. These results suggest that elevations in brain sAPPα levels are observed in subsets of individuals with autism and TgsAPPα mice display signs suggestive of gliosis and behavioral impairment.read more
Citations
More filters
Journal ArticleDOI
Not just amyloid: physiological functions of the amyloid precursor protein family
TL;DR: Focus is focused on the in vivo roles of APP family members and their processing products for CNS development, synapse formation and function, brain injury and neuroprotection, as well as ageing.
Journal ArticleDOI
Expression of A152T human tau causes age-dependent neuronal dysfunction and loss in transgenic mice.
Sumihiro Maeda,Biljana Djukic,Praveen Taneja,Gui Qiu Yu,Iris Lo,Allyson Davis,Ryan Craft,Weikun Guo,Xin Wang,Daniel Kim,Ravikumar Ponnusamy,T. Michael Gill,Eliezer Masliah,Lennart Mucke +13 more
TL;DR: The A152T substitution may augment risk for neurodegenerative diseases by increasing hTau protein levels, promoting network hyperexcitability, and synergizing with the adverse effects of other pathogenic factors.
Journal ArticleDOI
Therapeutic Potential of Secreted Amyloid Precursor Protein APPsα
TL;DR: These studies have revealed that either upregulating α-secretase activity, acutely administering APPs α or chronic delivery of APPsα via a gene therapy approach can effectively treat mouse models of Alzheimer’s disease (AD) and other disorders such as traumatic head injury.
Journal ArticleDOI
Altered expression of Alzheimer's disease-related genes in the cerebellum of autistic patients: a model for disrupted brain connectome and therapy
Fares Zeidán-Chuliá,B-Hn de Oliveira,Alla B. Salmina,Manuel F. Casanova,Daniel Pens Gelain,Mami Noda,Alexei Verkhratsky,Alexei Verkhratsky,Alexei Verkhratsky,J Cf Moreira +9 more
TL;DR: A model of NMDA glutamate receptor-mediated ERK activation of α-secretase activity and mitochondrial adaptation to apoptosis that may explain the early brain overgrowth and disruption of synaptic plasticity and connectome in autism is proposed.
Journal ArticleDOI
ADAM10 as a therapeutic target for brain diseases: from developmental disorders to Alzheimer's disease.
Elena Marcello,Barbara Borroni,Silvia Pelucchi,Silvia Pelucchi,Fabrizio Gardoni,Monica Di Luca +5 more
TL;DR: The most recent discoveries in understanding of the role of ADAM10 activity at the glutamatergic excitatory synapse are described and its involvement in the onset of neurodevelopmental and neurodegenerative disorders is described.
References
More filters
Journal ArticleDOI
Diagnostic and Statistical Manual of Mental Disorders
Vijay A. Mittal,Elaine F. Walker +1 more
TL;DR: An issue concerning the criteria for tic disorders is highlighted, and how this might affect classification of dyskinesias in psychotic spectrum disorders.
Journal ArticleDOI
Astrocytes: biology and pathology
TL;DR: Astrocyte functions in healthy CNS, mechanisms and functions of reactive astrogliosis and glial scar formation, and ways in which reactive astrocytes may cause or contribute to specific CNS disorders and lesions are reviewed.
Journal ArticleDOI
Neuroglial activation and neuroinflammation in the brain of patients with autism
Diana L. Vargas,Caterina Nascimbene,Caterina Nascimbene,Chitra Krishnan,Andrew W. Zimmerman,Andrew W. Zimmerman,Carlos A. Pardo +6 more
TL;DR: It is indicated that innate neuroimmune reactions play a pathogenic role in an undefined proportion of autistic patients, suggesting that future therapies might involve modifying neuroglial responses in the brain.
Journal ArticleDOI
Neuroanatomy of autism
TL;DR: It is suggested that the heterogeneity of both the core and co-morbid features predicts a heterogeneous pattern of neuropathology in autism, and defined phenotypes in larger samples of children and well-characterized brain tissue will be necessary for clarification of the neuroanatomy of autism.
Journal ArticleDOI
Cellular actions of beta-amyloid precursor protein and its soluble and fibrillogenic derivatives
TL;DR: Alternative enzymatic processing of beta-APP liberates A beta, which has a propensity to form amyloid fibrils; A beta can damage and kill neurons and increase their vulnerability to excitotoxicity.
Related Papers (5)
Increased Secreted Amyloid Precursor Protein-α (sAPPα) in Severe Autism: Proposal of a Specific, Anabolic Pathway and Putative Biomarker
FMRP Mediates mGluR5-Dependent Translation of Amyloid Precursor Protein
Cara J. Westmark,James S. Malter +1 more