Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
1.
Neurobiol Dis ; 151: 105273, 2021 04.
Article in English | MEDLINE | ID: mdl-33482356

ABSTRACT

Pathological hyperphosphorylated tau is a key feature of Alzheimer's disease (AD) and Frontotemporal dementia (FTD). Using transgenic mice overexpressing human non-mutated tau (htau mice), we assessed the contribution of tau to peripheral and central neurodegeneration. Indices of peripheral small and large fiber neuropathy and learning and memory performances were assessed at 3 and 6 months of age. Overexpression of human tau is associated with peripheral neuropathy at 6 months of age. Our study also provides evidence that non-mutated tau hyperphosphorylation plays a critical role in memory deficits. In addition, htau mice had reduced stromal corneal nerve length with preservation of sub-basal corneal nerves, consistent with a somatofugal degeneration. Corneal nerve degeneration occurred prior to any cognitive deficits and peripheral neuropathy. Stromal corneal nerve loss was observed in patients with FTD but not AD. Corneal confocal microscopy may be used to identify early neurodegeneration and differentiate FTD from AD.


Subject(s)
Cornea/diagnostic imaging , Cornea/pathology , Tauopathies/diagnostic imaging , Tauopathies/pathology , tau Proteins/metabolism , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/pathology , Animals , Female , Frontotemporal Dementia/diagnostic imaging , Frontotemporal Dementia/pathology , Humans , Memory Disorders/etiology , Mice , Mice, Transgenic , Microscopy, Confocal , Middle Aged , Nerve Degeneration/diagnostic imaging , Nerve Degeneration/pathology , Peripheral Nervous System Diseases/diagnostic imaging , Peripheral Nervous System Diseases/pathology
2.
J Neurosci Res ; 98(11): 2357-2369, 2020 11.
Article in English | MEDLINE | ID: mdl-32737929

ABSTRACT

Epidemiological studies have pointed at diabetes as a risk factor for Alzheimer's disease (AD) and this has been supported by several studies in animal models of both type 1 and type 2 diabetes. However, side-by-side comparison of the two types of diabetes is limited. We investigated the role of insulin deficiency and insulin resistance in the development of memory impairments and the effect of Exendin-4 (Ex4) treatment in a mouse model of AD. Three-4-month-old female wild type (WT) mice and mice overexpressing human tau and amyloid precursor protein (TAPP) were injected with streptozotocin (STZ) or fed a high-fat diet (HFD). A second study was performed in TAPP-STZ mice treated with Ex4, a long-lasting analog of GLP-1. Plasma and brain were collected at study termination for ELISA, Western blot, and immunohistochemistry analysis. Learning and memory deficits were impaired in TAPP transgenic mice compared with WT mice at the end of the study. Deficits were exaggerated by insulin deficiency in TAPP mice but 12 weeks of insulin resistance did not affect memory performances in either WT or TAPP mice. Levels of phosphorylated tau were increased in the brain of WT-STZ and TAPP-STZ mice but not in the brain of WT or TAPP mice on HFD. In the TAPP-STZ mice, treatment with Ex4 initiated after established cognitive deficits ameliorated learning, but not memory, impairments. This was accompanied by the reduction of amyloid ß and phosphorylated tau expression. Theses studies support the role of Ex4 in AD, independently from its actions on diabetes.


Subject(s)
Amyloid beta-Protein Precursor/genetics , Cognition Disorders/genetics , Exenatide/pharmacology , Hypoglycemic Agents/pharmacology , Insulin Resistance , Insulin/deficiency , tau Proteins/genetics , Animals , Brain Chemistry/drug effects , Brain Chemistry/genetics , Cognition Disorders/drug therapy , Cognition Disorders/psychology , Diabetes Mellitus, Experimental/psychology , Female , Humans , Male , Maze Learning/drug effects , Memory , Mice , Mice, Inbred C57BL , Mice, Inbred DBA , Mice, Transgenic , Obesity/metabolism , Obesity/psychology , Psychomotor Performance
SELECTION OF CITATIONS
SEARCH DETAIL
...