The Synthetic Retinoid Acitretin Increases IL-6 in the Central Nervous System of Alzheimer Disease Model Mice and Human Patients

Neuropeptide Y (NPY) is one of the most abundant protein transmitters in the central nervous system with roles in a variety of biological functions including: food intake, cardiovascular regulation, cognition, seizure activity, circadian rhythms, and neurogenesis. Reduced NPY and NPY receptor expression is associated with numerous neurodegenerative disorders including Alzheimer disease (AD). To determine whether replacement of NPY could ameliorate some of the neurodegenerative and behavioral pathology associated with AD, we generated a lentiviral vector expressing NPY fused to a brain transport peptide (apoB) for widespread CNS delivery in an APP-transgenic (tg) mouse model of AD. The recombinant NPY-apoB effectively reversed neurodegenerative pathology and behavioral deficits although it had no effect on accumulation of Aβ. The subgranular zone of the hippocampus showed a significant increase in proliferation of neural precursor cells without further differentiation into neurons. The neuroprotective and neurogenic effects of NPY-apoB appeared to involve signaling via ERK and Akt through the NPY R1 and NPY R2 receptors. Thus, widespread CNS-targeted delivery of NPY appears to be effective at reversing the neuronal and glial pathology associated with Aβ accumulation while also increasing NPC proliferation. Overall, increased delivery of NPY to the CNS for AD might be an effective therapy especially if combined with an anti-Aβ therapeutic.

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A Nanomule Peptide Carrier Delivers siRNA Across the Intact Blood-Brain Barrier to Attenuate Ischemic Stroke

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.611367 ◽

2021 ◽

Vol 8 ◽

Author(s):

Brett A. Eyford ◽

Chaahat S. B. Singh ◽

Thomas Abraham ◽

Lonna Munro ◽

Kyung Bok Choi ◽

...

Keyword(s):

Oxidative Stress ◽

Central Nervous System ◽

Nervous System ◽

Ischemic Stroke ◽

Blood Brain Barrier ◽

Disease Model ◽

Brain Barrier ◽

Blood Brain ◽

Peptide Carrier ◽

The Central Nervous System

The blood-brain barrier (BBB) hinders the distribution of therapeutics intended for treatment of neuroinflammation (NI) of the central nervous system. A twelve-amino acid peptide that transcytoses the BBB, termed MTfp, was chemically conjugated to siRNA to create a novel peptide-oligonucleotide conjugate (POC), directed to downregulate NOX4, a gene thought responsible for oxidative stress in ischemic stroke. The MTfp-NOX4 POC has the ability to cross the intact BBB and knockdown NOX4 expression in the brain. Following induction of ischemic stroke, animals pretreated with the POC exhibited significantly smaller infarcts; accompanied by increased protection against neurological deterioration and improved recovery. The data demonstrates that the MTfp can act as a nanomule to facilitate BBB transcytosis of siRNAs; where the NOX-4 specific siRNA moiety can elicit effective therapeutic knockdown of a gene responsible for oxidative stress in the central nervous system. This study is the first to conclusively demonstrate both siRNA-carrier delivery and therapeutic efficacy in any CNS disease model where the BBB remains intact and thus offers new avenues for potential treatments of oxidative stress underlying neuroinflammation in a variety of neuropathologies that are currently refractory to existing therapies.

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Decision letter for "Differential expression of five prosomatostatin genes in the central nervous system of the catshark Scyliorhinus canicula"

10.1002/cne.24898/v1/decision1 ◽

2019 ◽

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Differential Expression ◽

Scyliorhinus Canicula ◽

The Central Nervous System

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Review for "The central nervous system of whip spiders (Amblypygi): large mushroom bodies receive olfactory and visual input"

10.1002/cne.25045/v1/review1 ◽

2020 ◽

Author(s):

Harald Wolf

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Visual Input ◽

Mushroom Bodies ◽

The Central Nervous System

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Effects of Hyperoxia on Lung Utrastructure

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100067121 ◽

1970 ◽

Vol 28 ◽

pp. 26-27

Author(s):

Gladys Harrison

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Light Microscopy ◽

Oxygen Effects ◽

Age Dependent ◽

The Central Nervous System ◽

The Subject ◽

Space Age ◽

Alveolar Septa ◽

Extensive Damage

With the advent of the space age and the need to determine the requirements for a space cabin atmosphere, oxygen effects came into increased importance, even though these effects have been the subject of continuous research for many years. In fact, Priestly initiated oxygen research when in 1775 he published his results of isolating oxygen and described the effects of breathing it on himself and two mice, the only creatures to have had the “privilege” of breathing this “pure air”.Early studies had demonstrated the central nervous system effects at pressures above one atmosphere. Light microscopy revealed extensive damage to the lungs at one atmosphere. These changes which included perivascular and peribronchial edema, focal hemorrhage, rupture of the alveolar septa, and widespread edema, resulted in death of the animal in less than one week. The severity of the symptoms differed between species and was age dependent, with young animals being more resistant.

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Emigration of neutrophils in the central nervous system

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100077517 ◽

1983 ◽

Vol 41 ◽

pp. 788-789

Author(s):

John L.Beggs ◽

John D. Waggener ◽

Wanda Miller ◽

Jane Watkins

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Osmium Tetroxide ◽

White Blood Cells ◽

Arterial Perfusion ◽

E Coli ◽

Intracisternal Injection ◽

The Central Nervous System ◽

Brain And Spinal Cord ◽

Interendothelial Junctions

Studies using mesenteric and ear chamber preparations have shown that interendothelial junctions provide the route for neutrophil emigration during inflammation. The term emigration refers to the passage of white blood cells across the endothelium from the vascular lumen. Although the precise pathway of transendo- thelial emigration in the central nervous system (CNS) has not been resolved, the presence of different physiological and morphological (tight junctions) properties of CNS endothelium may dictate alternate emigration pathways.To study neutrophil emigration in the CNS, we induced meningitis in guinea pigs by intracisternal injection of E. coli bacteria.In this model, leptomeningeal inflammation is well developed by 3 hr. After 3 1/2 hr, animals were sacrificed by arterial perfusion with 3% phosphate buffered glutaraldehyde. Tissues from brain and spinal cord were post-fixed in 1% osmium tetroxide, dehydrated in alcohols and propylene oxide, and embedded in Epon. Thin serial sections were cut with diamond knives and examined in a Philips 300 electron microscope.

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Mammalian Bone Marrow Acetylcholinesterase

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100053024 ◽

1982 ◽

Vol 40 ◽

pp. 44-45

Author(s):

Ezzatollah Keyhani

Keyword(s):

Central Nervous System ◽

Bone Marrow ◽

Nervous System ◽

Common Property ◽

Extracellular Medium ◽

The Central Nervous System ◽

The Common ◽

Mammalian Bone

Acetylcholinesterase (EC 3.1.1.7) (ACHE) has been localized at cholinergic junctions both in the central nervous system and at the periphery and it functions in neurotransmission. ACHE was also found in other tissues without involvement in neurotransmission, but exhibiting the common property of transporting water and ions. This communication describes intracellular ACHE in mammalian bone marrow and its secretion into the extracellular medium.

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