Generation of Alzheimer's Disease Transgenic Zebrafish Expressing Human APP Mutation Under Control of Zebrafish appb Promotor.

Background: Amyloid peptide precursor (APP) as the precursor protein of peptide betaamyloid (β-amyloid, Aβ), which is thought to play a central role in the pathogenesis of Alzheimer's disease (AD), also has an important effect on the development and progression of AD. Through knocking-in APP gene in animals, numerous transgenic AD models have been set up for the investigation of the mechanisms behind AD pathogenesis and the screening of anti-AD drugs. However, there are some limitations to these models and here is a need for such an AD model that is economic as well as has satisfactory genetic homology with human.

[Zebrafish as a model animal for the study of blood-brain barrier permeability by biomolecules].

Blood-brain barrier (BBB) is the major obstacle for drug delivery into the central nervous system (CNS). However, there is no ideal model animal for the study of BBB permeability till now. Currently zebrafish (Danio rerio) has emerged as a powerful model organism for the study of vertebrate biology.

Single intravenous injection of plasmid DNA encoding human paraoxonase-1 inhibits hyperlipidemia in rats.

Paraoxonase-1 (PON1, EC 3.1.8.

Thyroid hormone prevents cognitive deficit in a mouse model of Alzheimer's disease.

This study aimed to examine the feasibility of using thyroid hormone (TH) as a therapeutic agent for Alzheimer's disease (AD). Mice were injected intra-hippocampally aggregated amyloid beta-peptide (Abeta) to produce AD animal model. Intraperitoneal administration of l-thyroxine (L-T4) into Abeta-induced AD model mice prevented their cognitive impairment and improved their memory function.

Down-regulation of beta1-adrenoceptors gene expression by short interfering RNA impairs the memory retrieval in the basolateral amygdala of rats.

The influence of basolateral amygdala (BLA) on memory is known to depend critically on adrenergic neurotransmission. However, the roles of noradrenergic receptors on memory retrieval have been elusive and controversial. Here, we investigated the effect of beta(1)-adrenoceptor (beta(1)-AR) on auditory fear memory in the rat BLA.

A novel therapeutic approach to depression via supplement with tyrosine hydroxylase.

Tyrosine hydroxylase (tyrosine 3-monooxygenase, EC 1.14.16.

Protective effect of N-acetyl-L-cysteine on amyloid beta-peptide-induced learning and memory deficits in mice.

This study aimed to examine the effects of N-acetyl-L-cysteine (NAC) on protecting neurons function and improving learning and memory deficits in mice. Mice were intracerebroventricularly (icv) injected with the aggregated amyloid beta-peptide (Abeta) to produce Alzheimer's disease (AD). Learning and memory functions in mice were examined by the step through test and the water maze performance.

A novel therapeutic approach to 6-OHDA-induced Parkinson's disease in rats via supplementation of PTD-conjugated tyrosine hydroxylase.

The present study aimed to evaluate whether the protein transduction domain (PTD)-conjugated human tyrosine hydroxylase (TH) fusion protein was effective on the 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease (PD) model rats. An expression vector pET-PTD-TH harbouring the PTD-TH gene was constructed and transformed to the Escherichia coli BL21 cells for expression. The expressed recombinant PTD-TH with a molecular weight of 61 kD was successfully transduced (1 microM) into the dopaminergic SH-sy5y human neuroblastoma cells in vitro and visualized by immunohistochemical assay.

Antisense inhibition of acetylcholinesterase gene expression for treating cognition deficit in Alzheimer's disease model mice.

To examine whether the selected antisense oligodeoxynucleotides (AS-ODN) targeting against human brain acetylcholinesterase (AChE) mRNA could improve the cognitive deficit in the Alzheimer's disease (AD) model mice induced by amyloid-beta peptide (Abeta), we determined the time-effect relationship of AChE activity and the learning and memory after AS-ODN delivery. The results showed that the AChE activity decreased gradually along with time, initiating at 8 h and lasting 42 h. The time-effect curves of acetylcholine (ACh) behaved consistency with that of AChE activity.

Complementary remedy of aged-related learning and memory deficits via exogenous choline acetyltransferase.

The present study aimed to examine whether the aged mice with naturally occurring cognitive deficits in learning and memory would benefit from supplementation of choline acetyltransferase (ChAT), the biosynthetic enzyme for neurotransmitter acetylcholine. Delivered by protein transduction domain (PTD), ChAT could pass through the blood-brain barrier, enter the neurons, interact with heat shock protein 70kDa, and retain enzyme activity. In behavior tests, PTD-ChAT given to the aged and memory-deficient mice almost completely reversed the behavioral changes, such as impairment of memory retention in the step-through test (an index of long-term memory) and prolonged swimming time in water maze test (an index of spatial recognition memory).

Naked DNA prevents soman intoxication.

Paraoxonase (Q isoenzyme, PON1) can effectively hydrolyze chlorpyrifos-oxon (CPO), soman, sarin, and other organophosphates. Previous studies had indicated that the levels of serum PON1 in gene therapy with adenoviral vector could decrease the toxicity of CPO. In our study, plasmid pcDNA/PON1 injected into the tail vein of mice gave excellent expression at 24h after delivery, and PON1 activity decreased gradually along with days.

Alteration of binding sites for [3H]P1075 and [3H]glibenclamide in renovascular hypertensive rat aorta.

Aim: The alterations of the binding sites for ATP-sensitive K+ channel (K(ATP)) openers and blockers in aortic strips were investigated in hypertensive rats.

Methods: Radioligand binding techniques were used to compare the specific binding properties of [3H]P1075 and [3H]glibenclamide (Gli) in normotensive (NWR) and reno-vascular hypertensive rat (RVHR) aortic strips.

Results: The KD values of [3H]P1075 binding were increased by 1.

Alternative therapy of Alzheimer's disease via supplementation with choline acetyltransferase.

Much evidence indicates that the memory and cognitive deficits of patients with Alzheimer's disease are closely associated with dysfunction of central cholinergic system. The degree of reduction of choline acetyltransferase activity in cerebral cholinergic neurons is significantly correlated with the severity of dementia or cognitive impairments observed in Alzheimer's disease. Therefore, Alzheimer's disease may be slowed by supplementation of exogenous choline acetyltransferase.