Your search for: 'author:("Lazarov, Orly")' has returned 4 results. (0.014s) Save search

Authors: Little, Deborah M. | Foxely, Sean | Lazarov, Orly

Article Type: Research Article

Abstract: We have shown that experience of transgenic mice harboring familial Alzheimer's disease (FAD)-linked AβPPswe/PS1ΔE9 in an enriched environment enhances hippocampal neurogenesis and synaptic plasticity and attenuates neuropathology. Nevertheless, the neuronal pathways activated following environmental enrichment underlying this effect are unknown. Using resting-state functional magnetic resonance imaging, we present preliminary evidence to show that transgenic mice, which had been housed in an enriched environment, show increased connectivity between CA1 and cortical areas compared to mice from standard housing. This is the first preliminary demonstration of live-activated neuronal pathways following environmental enrichment in FAD mice. Understanding the activated pathways may unravel the …molecular mechanism underlying environmental enrichment-enhanced neuroplasticity in FAD. Show more

Keywords: Alzheimer's disease, brain plasticity, environmental enrichment, resting state functional MRI

DOI: 10.3233/JAD-2012-111508

Citation: Journal of Alzheimer's Disease, vol. 32, no. 1, pp. 101-107, 2012

Authors: Bartolotti, Nancy | Segura, Laura | Lazarov, Orly

Article Type: Research Article

Abstract: The mechanism underlying impaired learning and memory in Alzheimer’s disease is not fully elucidated. The phosphorylation of cyclic-AMP response element binding protein (pCREB) in the hippocampus is thought to be a critical initiating step in the formation of long-term memories. Here, we tested CRE-driven gene expression following learning in mice harboring the familial Alzheimer’s disease-linked APPswe/PS1ΔE9 mutations using CRE-β galactosidase reporter. We show that young adult APPswe/PS1ΔE9 mice exhibit impaired recognition memory and reduced levels of pCREB, and its cofactors CREB binding protein (CBP) and p-300 following a learning task, compared to their wild type littermate counterparts. Impairments in learning-induced …activation of CREB in these mice are manifested by reduced CRE-driven gene transcription. Importantly, expression of the CRE-driven immediate early gene, Egr-1 (Zif268) is decreased in the CA1 region of the hippocampus. These studies implicate defective CREB-dependent plasticity in the mechanism underlying learning and memory deficits in Alzheimer’s disease. Show more

Keywords: Alzheimer’s disease, CBP, CRE, CREB, hippocampal plasticity, learning and memory

DOI: 10.3233/JAD-150650

Citation: Journal of Alzheimer's Disease, vol. 50, no. 2, pp. 477-489, 2016

Authors: Bartolotti, Nancy | Disouky, Ahmed | Kalinski, Arthur | Elmann, Anat | Lazarov, Orly

Article Type: Research Article

Abstract: Plant derivatives offer a novel and natural source of therapeutics. The desert plant Achillea fragrantissima (Forssk) Sch. Bip (Af) is characterized by protective antioxidative and anti-inflammatory properties. Here, we examined the effect of two Af -derived phytochemicals on learning and memory, amyloid-β protein precursor (AβPP) metabolism, and tau phosphorylation in the familial Alzheimer’s disease-linked APPswe/PS1Δ E9 mouse model. We observed that mice that were injected with the phytochemicals showed a trend of improvement, albeit statistically insignificant, in the Novel Object Recognition task. However, we did not observe improvement in contextual fear conditioning, suggesting that the benefits of treatment may be …either indirect or task-specific. In addition, we observed an increase in the full-length form of AβPP in the brains of mice treated with Af –derived phytochemicals. Interestingly, both in vivo and in vitro , there was no change in levels of soluble Aβ, oligomeric Aβ, or the carboxyl terminus fragments of AβPP (APP-CTFs), suggesting that the increase in full length AβPP does not exacerbate AβPP pathology, but may stabilize the full-length form of the molecule. Together, our data suggest that phytochemicals present in Af may have a modest positive impact on the progression of Alzheimer’s disease. Show more

Keywords: Achillolide A, Alzheimer’s disease, amyloid-β protein precursor, flavonoids, sesquiterpene lactones, 3, 5, 4’-trihydroxy-6, 7, 3’-trimethoxyflavone

DOI: 10.3233/JAD-180068

Citation: Journal of Alzheimer's Disease, vol. 66, no. 4, pp. 1425-1435, 2018

Authors: Kuttner-Hirshler, Yafit | Venkatasubramanian, Palamadai N. | Apolinario, Joan | Bonds, Jacqueline | Wyrwicz, Alice M. | Lazarov, Orly

Article Type: Research Article

Abstract: Alzheimer’s disease (AD) is characterized by progressive loss of memory and cognitive deterioration. It is thought that the onset of the disease takes place several decades before memory deficits are apparent. Reliable biomarkers for the diagnosis or prognostication of the disease are highly desirable. Neural stem cells (NSC) exist in the adult brain throughout life and give rise to neural progenitor cells (NPC), which differentiate into neurons or glia. The level of NPC proliferation and new neuron formation is significantly compromised in mouse models of familial Alzheimer’s disease (FAD). These deficits are readily detected in young adults, at 2-3 months …of age, preceding amyloid deposition and cognitive impairments, which may indicate that impaired neurogenesis can be an early biomarker for cognitive deficits in AD. Recent studies suggest that NSC can be detected in live rodents, noninvasively, using proton magnetic resonance spectroscopy (1 H-MRS) signal at 1.28 ppm. Here we examined the use of 1 H-MRS for determining the extent of neurogenesis in the brains of FAD mice. We observed that the reduction in neurogenesis in the FAD mice as observed by immunohistochemistry, was not manifested by a reduction in the 1.28 ppm signal, suggesting that this marker is either not specific for neurogenesis or not sensitive enough for the detection of alterations in hippocampal neurogenesis in the brains of FAD mice. Show more

Keywords: Alzheimer’s disease, brain biomarkers, 1H-MRS, mouse models, neurogenesis

DOI: 10.3233/JAD-170269

Citation: Journal of Alzheimer's Disease, vol. 60, no. 3, pp. 949-958, 2017