Sleep deprivation, shift work, and jet lag all disrupt normal biological rhythms have major impacts on health; however, circadian disorganization has never been shown as a causal risk factor in organ disease. We now demonstrate devastating effects of rhythm cardiovascular renal integrity that interventions based principles prevent disease pathology caused by short-period mutation (tau) the system hamsters. The point regulatory gene, casein kinase-1epsilon, produces early onset entrainment...

Alzheimer's disease (AD), pathologically characterized by amyloid-β peptide (Aβ) accumulation, neurofibrillary tangle formation, and neurodegeneration, is thought to involve early-onset neurovascular abnormalities. Hitherto studies on AD-associated injury have used animal models that exhibit only a subset of AD-like pathologies demonstrated some Aβ-dependent vascular dysfunction destabilization neuronal network. The present work focuses the early stage progression uses TgF344-AD rats...

Abstract Alzheimer's disease ( AD ) is pathologically characterized by amyloid‐β peptide (Aβ) accumulation, neurofibrillary tangle formation, and neurodegeneration. Preclinical studies on neuronal impairments associated with progressive amyloidosis have demonstrated some Aβ‐dependent dysfunction including modulation of gamma‐aminobutyric acid‐ergic signaling. The present work focuses the early stage progression uses TgF344‐ rats that recapitulate a broad repertoire ‐like pathologies to...

The distinct lack of cell lines derived from the adult brain is evident. Ciliary neurotrophic factor (CNTF) triggers neurogenesis in primary culture mouse hypothalamus, as detected by bromodeoxyuridine and Ki67 immunostaining. Using SV-40 T-antigen, we immortalized dividing neurons generated clonal expressing neuropeptides receptors involved neuroendocrine function. We hypothesized that proglucagon-derived peptides may be mechanistic downstream effectors CNTF due to documented...

Most patients with Alzheimer's disease exhibit accumulation of amyloid-β peptide on leptomeningeal and cortical arterioles, or cerebral amyloid angiopathy, which is associated impaired vascular reactivity accelerated cognitive decline. Despite widespread recognition the significance dysfunction in aetiology progression, much uncertainty still surrounds mechanism underlying injury. Studies to date have focused amyloid-β-induced damage capillaries plaque-associated without examining effects...

Failure of Alzheimer's disease clinical trials to improve or stabilize cognition has led the need for a better understanding driving forces behind cognitive decline in presence active processes. To dissect contributions individual pathologies function, we used TgF344-AD rat model, which recapitulates salient hallmarks pathology observed patient populations (amyloid, tau inclusions, frank neuronal loss, and deficits). scyllo-Inositol treatment attenuated amyloid-β peptide disease-bearing...

Ex vivo 2-photon fluorescence microscopy (2PFM) with optical clearing enables vascular imaging deep into tissue. However, may also produce spherical aberrations if the objective lens is not index-matched to material, while perfusion, clearing, and fixation procedure alter morphology. We compared in ex 2PFM mice, focusing on apparent differences microvascular signal Following imaging, mice (four total) were perfused a fluorescent gel their brains fructose-cleared. The brain regions imaged...

The mammalian master clock, located in the suprachiasmatic nucleus (SCN), is exquisitely sensitive to photic timing cues, but key molecular events that sculpt both phasing and magnitude of responsiveness are not understood. Here, we show Ras-like G-protein Dexras1 a critical factor these processes. -deficient mice ( dexras1 −/− ) exhibit restructured nighttime phase response curve loss gating resetting during day. affects sensitivity by repressing or activating time-of-day-specific signaling...

Abstract Longitudinal studies using two–photon fluorescence microscopy (TPFM) are critical for facilitating cellular scale imaging of brain morphology and function. Studies have been conducted in the mouse due to their relatively higher transparency long term patency a chronic cranial window. Increasing availability transgenic rat models, range established behavioural paradigms, necessitates development preparation rat. However, surgical craniotomies present challenges craniotomy closure by...

Background and Purpose— Recent evidence suggests great potential of metabolically targeted interventions for treating neurological disorders. We investigated the use endogenous ketone body β-hydroxybutyrate (BHB) as an alternate metabolic substrate brain in acute phase ischemia because postischemic hyperglycemia glucose metabolism elevation compromise functional recovery. Methods— delivered BHB (or vehicle) 1 hour after ischemic insult induced by cortical microinjection endothelin-1...

Functional hyperaemia is a well-established hallmark of healthy brain function, whereby local blood flow adjusts in response to change the activity surrounding neurons. Although functional hyperemia has been extensively studied at level both tissue and individual vessels, vascular network-level coordination remains largely unknown. To bridge this gap, we developed deep learning-based computational pipeline that uses two-photon fluorescence microscopy images cerebral microcirculation enable...

We report on a miniature label-free imaging system for monitoring brain blood flow and oxygenation changes in awake, freely behaving rats. The device, weighing 15 grams, enables ∼ 2 × mm field of view with 4.4 μm lateral resolution 1 - 8 Hz temporal sampling rate. is performed through chronically-implanted cranial window that remains optically clear between to > 6 weeks after the craniotomy. This method well suited longitudinal studies chronic models diseases disorders. In this work, it...

Aerobic activity has been shown highly beneficial to brain health, yet much uncertainty still surrounds the effects of exercise on functioning cerebral microvasculature. This study used two-photon fluorescence microscopy examine hemodynamic alterations as well accompanying geometric changes in cortical microvascular network following five weeks voluntary transgenic mice endogenously expressing tdTomato vascular endothelial cells allow visualization microvessels irrespective their perfusion...

ABSTRACT Obesity reduces or increases the risk of developing Alzheimer’s disease (AD) depending on whether it is assessed in mid-life late-life. There currently no consensus relationship between obesity and AD mechanism their interaction. Here, we aim to differentiate cause-and-effect a controlled rat model AD. We induced 9-month-old TgF344-AD rats, that pathology-load wise similar early symptomatic phase human To more accurately obesity, fed both non-transgenic littermates varied...

Loss of Dexras1 in gene-targeted mice impairs circadian entrainment to light cycles and produces complex changes phase-dependent resetting responses (phase shifts) light. The authors now describe greatly enhanced phase-specific nonphotic induced by arousal dexras1−/− mice. In constant conditions, mutant exhibited significant arousal-induced phase shifts throughout the subjective day. Unusual advances late night were also produced when has little effect Bilateral lesions intergeniculate...

The pituitary is a complex endocrine tissue composed of number unique cell types distinguished by the expression and secretion specific hormones, which in turn control critical components overall physiology. basic function these cells understood; however, molecular events involved their hormonal regulation are not yet fully defined. While previously established lines have provided much insight into regulatory mechanisms, availability representative from each lineage limited, currently none...

The ability of MRI to differentiate between normal and radioresistant cancer was investigated in prostate tumour xenografts mice. Specifically, the process magnetization exchange water other molecules studied. It found that transfer from semisolid macromolecules (MT) chemical saturation (CEST) combined were significantly different groups (p < 0.01). Further, T2 relaxation macromolecular pool (T2,B), a parameter specific MT, be Also rNOE contributions associated with methine at -0.9 ppm B1...

Abstract A role for arginine vasopressin in the circadian regulation of voluntary locomotor behavior (wheel running activity) was investigated golden hamster, M esocricetus auratus . Spontaneous nocturnal suppressed a dose‐dependent manner by systemic injections vasopressin, and also concentration‐dependent microinjections directly into hypothalamic suprachiasmatic nucleus. Pre‐injections V1 receptor antagonist nucleus reduced suppression vasopressin. Ethogram analyses revealed that...

Abstract Circadian activity rhythms in mammals are controlled by the expression and transcriptional regulation of clock genes suprachiasmatic nucleus (SCN). The circadian cycle length hamsters is regulated part casein kinase I epsilon (CKIε). A semidominant mutation (C→T, R178C, CKIε tau ) appears to act as a dominant‐negative allele shorten period rhythms. We tested this hypothesis vivo expressing wild‐type gene homozygous mutant hamsters. High‐level +/+ transfer (as indicated green...

Transient hypertension is a risk factor for Alzheimer disease (AD), but the effects of this interaction on brain vasculature are understudied. Addressing vascular pathology promising avenue to potentiate efficacy treatments AD. We used arterial spin labeling magnetic resonance imaging longitudinally assess function and immunohistopathology examine cerebrovascular remodeling amyloid load. Hypertension was induced 1 month by administration l-NG-nitroarginine-methyl-ester in TgF344-AD rats at...