Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 3 de 3
Filter
Add more filters










Database
Language
Publication year range
1.
Front Neurosci ; 14: 574499, 2020.
Article in English | MEDLINE | ID: mdl-33071746

ABSTRACT

The oxytocin receptor (OXTR) is a G protein-coupled receptor with a diverse repertoire of intracellular signaling pathways, which are activated in response to binding oxytocin (OXT) and a similar nonapeptide, vasopressin. This review summarizes the cell and molecular biology of the OXTR and its downstream signaling cascades, particularly focusing on the vasoactive functions of OXTR signaling in humans and animal models, as well as the clinical applications of OXTR targeting cerebrovascular accidents.

2.
J Alzheimers Dis ; 70(2): 371-388, 2019.
Article in English | MEDLINE | ID: mdl-31177220

ABSTRACT

Noradrenergic locus coeruleus (LC) neuron loss is a significant feature of mild cognitive impairment and Alzheimer's disease (AD). The LC is the primary source of norepinephrine in the forebrain, where it modulates attention and memory in vulnerable cognitive regions such as prefrontal cortex (PFC) and hippocampus. Furthermore, LC-mediated norepinephrine signaling is thought to play a role in blood-brain barrier (BBB) maintenance and neurovascular coupling, suggesting that LC degeneration may impact the high comorbidity of cerebrovascular disease and AD. However, the extent to which LC projection system degeneration influences vascular pathology is not fully understood. To address this question in vivo, we stereotactically lesioned LC projection neurons innervating the PFC of six-month-old Tg344-19 AD rats using the noradrenergic immunotoxin, dopamine-ß-hydroxylase IgG-saporin (DBH-sap), or an untargeted control IgG-saporin (IgG-sap). DBH-sap-lesioned animals performed significantly worse than IgG-sap animals on the Barnes maze task in measures of both spatial and working memory. DBH-sap-lesioned rats also displayed increased amyloid and inflammation pathology compared to IgG-sap controls. However, we also discovered prominent parenchymal albumin extravasation with DBH-sap lesions indicative of BBB breakdown. Moreover, microvessel wall-to-lumen ratios were increased in the PFC of DBH-sap compared to IgG-sap rats, suggesting that LC deafferentation results in vascular remodeling. Finally, we noted an early emergence of amyloid angiopathy in the DBH-sap-lesioned Tg344-19 AD rats. Taken together, these data indicate that LC projection system degeneration is a nexus lesion that compromises both vascular and neuronal function in cognitive brain areas during the prodromal stages of AD.


Subject(s)
Alzheimer Disease/pathology , Blood-Brain Barrier/pathology , Disease Models, Animal , Locus Coeruleus/pathology , Nerve Degeneration/pathology , Prosencephalon/pathology , Alzheimer Disease/genetics , Animals , Female , Humans , Locus Coeruleus/blood supply , Male , Maze Learning/physiology , Mice , Nerve Degeneration/genetics , Prosencephalon/blood supply , Rats , Rats, Inbred F344 , Rats, Transgenic
3.
J Neuropathol Exp Neurol ; 78(5): 436-452, 2019 05 01.
Article in English | MEDLINE | ID: mdl-30990880

ABSTRACT

Vascular dementia (VaD) is cognitive decline linked to reduced cerebral blood perfusion, yet there are few therapeutic options to protect cognitive function following cerebrovascular accidents. The purpose of this study was to profile gene expression changes unique to VaD to identify and characterize disease relevant changes that could offer clues for future therapeutic direction. Microarray-based profiling and validation studies of postmortem frontal cortex samples from VaD, Alzheimer disease, and age-matched control subjects revealed that the oxytocin receptor (OXTR) was strongly and differentially upregulated in VaD. Further characterization in fixed tissue from the same cases showed that OXTR upregulation occurs de novo around and within microinfarcts in peri-infarct reactive astrocytes as well as within vascular profiles, likely on microvascular endothelial cells. These results indicate that increased OXTR expression in peri-infarct regions may be a specific response to microvascular insults. Given the established OXTR signaling cascades that elicit antioxidant, anti-inflammatory, and pro-angiogenic responses, the present findings suggest that de novo OXTR expression in the peri-infarct space is a tissue-protective response by astroglial and vascular cells in the wake of ischemic damage that could be exploited as a therapeutic option for the preservation of cognition following cerebrovascular insults.


Subject(s)
Cerebral Infarction/metabolism , Dementia, Vascular/metabolism , Frontal Lobe/metabolism , Receptors, Oxytocin/biosynthesis , Up-Regulation/physiology , Aged , Aged, 80 and over , Cerebral Infarction/genetics , Cerebral Infarction/pathology , Dementia, Vascular/genetics , Dementia, Vascular/pathology , Female , Frontal Lobe/pathology , Gene Regulatory Networks/physiology , Humans , Male , Middle Aged , Receptors, Oxytocin/genetics
SELECTION OF CITATIONS
SEARCH DETAIL
...