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Pregnane x receptors (PXRs) regulate the expression of ATP-binding cassette proteins transporters and organic anion transporting polypeptides responsible for influx/efflux of xenobiotics across brain. Ligand activation of PXR augments the expression of P-gp and promotes Aβ clearance across the blood brain barrier. Dementia was induced in mice by intacerebroventricular administration of streptozotocin (STZ), followed by treatment with meclizine, a PXR agonist and subsequently exposed to Morris water maze test and biochemical analysis to evaluate the effect on cognition. STZ-treated mice exhibited significant enhancement in brain thiobarbituric acid reactive species, interleukin-1β, tumour necrosis factor-α, myeloperoxidase and acetylcholinestrase activity in addition to diminution in glutathione levels and superoxide dismutase activity in comparison to untreated mice. Administration of meclizine to STZ mice recuperated cognition and biochemical alterations. Concomitant administration of ketoconazole, a PXR antagonist with meclizine prevented the protective effects. The upshots of our study proclaim that meclizine protects cognitive deficits by virtue of its antioxidant, anti-cholinesterase and anti-inflammatory properties. Results also signify the potential of PXR in neuroprotective actions of meclizine in dementia.
This article was published in the following journal.
Name: Canadian journal of physiology and pharmacology
Alzheimer's disease (AD) is a neurodegenerative disease and a common cause of dementia, manifesting as progressive memory loss and cognitive decline. Moscatilin, which reportedly reduces fever and is ...
Our previous data indicated that tanshinone IIA (tan IIA) improves learning and memory in a mouse model of Alzheimer's disease (AD) induced by streptozotocin via restoring cholinergic function, attenu...
Intracerebroventricular (icv) streptozotocin (STZ) injection decreases cerebral insulin signal pathway function and produces multiple effects that resemble the molecular, pathological, and behavioural...
Oxiracetam ameliorates cognitive deficits in vascular dementia rats by regulating the expression of neuronal apoptosis/autophagy-related genes associated with the activation of the Akt/mTOR signaling pathway.
Oxiracetam (ORC) is a commonly used nootropic drug for improving cognition and memory impairments. The therapeutic effect and underlying mechanism of ORC in vascular dementia (VaD) treatment remain un...
Background Natural medicinal plants have been the focus of current research for developing neuroprotective agents to be used in the diabetes-linked cognitive dysfunction. Trigonella foenum-graecum see...
Memory deficits after brain damage are common and there is still a need for evaluated therapy methods. In this study we compare two therapeutic interventions and investigate whether therap...
Meclizine hydrochloride is an antihistamine widely used for treatment of vertigo and motion sickness. In HCC it has been used for anti-emetic effects, but it is used here as a CAR (constit...
The study hypothesizes that donepezil will have a positive impact on brain blood flow deficits in subjects with memory deficits and/or mild dementia and that improvements in brain blood fl...
This project is based on a three-year program that aims to improve the knowledge of the socioeconomic consequences of dementia in Norway. By including patients with and without dementia in...
Alzheimer's disease often manifests as a memory disorder before dementia develops. Dementia is considered to be present when a person can no longer handle complex activities of daily livin...
Disturbances in registering an impression, in the retention of an acquired impression, or in the recall of an impression. Memory impairments are associated with DEMENTIA; CRANIOCEREBRAL TRAUMA; ENCEPHALITIS; ALCOHOLISM (see also ALCOHOL AMNESTIC DISORDER); SCHIZOPHRENIA; and other conditions.
ARTHRITIS that is induced in experimental animals. Immunological methods and infectious agents can be used to develop experimental arthritis models. These methods include injections of stimulators of the immune response, such as an adjuvant (ADJUVANTS, IMMUNOLOGIC) or COLLAGEN.
Type of declarative memory, consisting of personal memory in contrast to general knowledge.
Loss of the ability to form new memories beyond a certain point in time. This condition may be organic or psychogenic in origin. Organically induced anterograde amnesia may follow CRANIOCEREBRAL TRAUMA; SEIZURES; ANOXIA; and other conditions which adversely affect neural structures associated with memory formation (e.g., the HIPPOCAMPUS; FORNIX (BRAIN); MAMMILLARY BODIES; and ANTERIOR THALAMIC NUCLEI). (From Memory 1997 Jan-Mar;5(1-2):49-71)
Drugs used to specifically facilitate learning or memory, particularly to prevent the cognitive deficits associated with dementias. These drugs act by a variety of mechanisms. While no potent nootropic drugs have yet been accepted for general use, several are being actively investigated.
Of all the types of Dementia, Alzheimer's disease is the most common, affecting around 465,000 people in the UK. Neurons in the brain die, becuase 'plaques' and 'tangles' (mis-folded proteins) form in the brain. People with Al...
Dementia describes a range of symptoms of cognitive decline. For example memory loss, problems with reasoning and communication skills, and a reduction in a person's abilities and skills in carrying out daily activities. There are about 820,000 peo...
Cytokine Tumour Necrosis Factor (TNF)
TNF is a compound that is classified as a cytokine which plays a central role in the cellular mechanisms of apoptosis or cell death. However, there are a number of different kinds of TNF, just under twenty, but the family of molecules have very similar a...