The State of The Art on Acetylcholinesterase Inhibitors in the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is a chronic disabling disease that affects the central nervous system. The main consequences of AD include the decline of cognitive functions and language disorders. One of the causes leading to AD is the decrease of neurotransmitter acetylcholine (ACh) levels in the brain, in part due to a higher activity of acetylcholinesterase (AChE), the enzyme responsible for its degradation.

The Sphingosine 1-Phosphate Signaling Pathway in Epilepsy: A Possible Role for the Immunomodulator Drug Fingolimod in Epilepsy Treatment.

It is currently known that erythrocytes are the major source of sphingosine 1-phosphate (S1P) in the body. S1P acts both extracellularly as a cellular mediator and intracellularly as an important second messenger molecule. Its effects are mediated by interaction with five specific types of G proteincoupled S1P receptor.

Antiepileptogenic effects of the selective COX-2 inhibitor etoricoxib, on the development of spontaneous absence seizures in WAG/Rij rats.

Different data suggest the involvement of specific inflammatory pathways in the pathogenesis of epilepsy. Cyclooxygenase (COX), which catalyses the production of pro-inflammatory prostaglandins, may play a significant role in seizure-induced neuroinflammation and neuronal hyperexcitability. COX-2 is constitutively expressed in the brain and also increased during/after seizures.

Long-term betamethasone 21-phosphate disodium treatment has distinct effects in CD1 and DBA/2 mice on animal behavior accompanied by opposite effects on neurogenesis.

One of the most peculiar characteristics of the stress response is the pronounced inter-individual and inter-strain variability both in behavioral and neurochemical outcomes. Several studies confirm that rodents belonging to the same or different strain and/or gender, when exposed to a stressor, may show behavioral and cognitive differences. We compared the effects of long-term betamethasone 21-phosphate disodium (BTM), a widely clinically used corticosteroid, on animal behavior and neurogenesis in CD1 and DBA/2 mice.

Lamotrigine positively affects the development of psychiatric comorbidity in epileptic animals, while psychiatric comorbidity aggravates seizures.

Several clinical and preclinical studies have focused on the relationship between epilepsy and psychological disturbances. Although behavior in some experimental models of epilepsy has been studied, only few of them can be considered as models of epilepsy and mood disorder comorbidity. Since several models of epilepsy or psychiatric disorders are already available, we wondered whether a mixture of the two could experimentally represent a valid alternative to study such comorbidity.

Huperzine a restores cortico-hippocampal functional connectivity after bilateral AMPA lesion of the nucleus basalis of meynert.

Huperzine A (Hup-A), an alkaloid isolated from Huperzia serrata (Thunb.) Trevis. (Lycopodiaceae), acts as a selective inhibitor of acetylcholinesterase and shows memory-enhancing properties.

Vigabatrin has antiepileptogenic and antidepressant effects in an animal model of epilepsy and depression comorbidity.

To evaluate the effects of Vigabatrin (VGB) treatment, on both absence seizure and depressive-like behaviour development in the WAG/Rij rat model of absence seizures. Early long-term treatment with VGB could alter the development of absence pathology, by significantly reducing seizure generation and synchronization in contrast to its pro-absence effects observed after acute or subchronic administration. We have demonstrated the antidepressant effects of a sub-chronic treatment with VGB in both wistar and WAG/Rij rats.

Enhancement of anti-absence effects of ethosuximide by low doses of a noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist in a genetic animal model of absence epilepsy.

N-Acetyl-1-(4-chlorophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (THIQ-10c) is a noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist that has been demonstrated to antagonize generalized tonic-clonic seizures in different animal models of epilepsy. In the study described here, we tested the potential effect of such a compound alone or co-administered with ethosuximide in a genetic animal model of absence epilepsy, the WAG/Rij rat. The intraperitoneal or intracerebroventricular microinjection of THIQ-10c alone was unable to significantly modify the number and duration of spike-and-wave discharges (SWDs).

Choline pivaloyl ester enhances brain expression of both nerve growth factor and high-affinity receptor TrkA, and reverses memory and cognitive deficits, in rats with excitotoxic lesion of nucleus basalis magnocellularis.

The aim of present work was the evaluation of the effects on brain levels of nerve growth factor (NGF) and of its high-affinity tyrosine kinase A receptor (TrkA), induced in rats unilaterally lesioned at nucleus basalis magnocellularis (NBM), by treatment with choline pivaloyl ester (CPE). CPE was daily administered (60 micromol/Kg ip) during 3 weeks to rats selectively lesioned by AMPA infusion into right NBM; the intact left NBM serving as control. NGF levels were determined in cerebral cortex and hippocampus by Elisa assay.

Effects of some neurosteroids injected into some brain areas of WAG/Rij rats, an animal model of generalized absence epilepsy.

Neurosteroids are synthesized in the brain and have been demonstrated to modulate various cerebral functions. Allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one), a naturally occurring neurosteroid, and ganaxolone (3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one), a synthetic derivative, are two neurosteroids acting as positive allosteric modulators of the GABA(A) receptor complex acting on a specific steroid recognition site. Both agents antagonize generalized tonic-clonic seizures in various animal models of epilepsy.

Electroencephalographic effects induced by choline pivaloyl esters in scopolamine-treated or nucleus basalis magnocellularis lesioned rats.

The electroencephalographic (EEG) effects of two choline pivaloyl esters, [2-(2,2-dimethylpropionyloxy)ethyl]trimethylammonium iodide (1) and [2-(2,2-dimethylpropionyloxy)ethyl]trimethylammonium 2,2-dimethylpropionate (2), were evaluated in scopolamine-treated or nucleus basalis magnocellularis (NBM) lesioned rats. In scopolamine-treated animals, Compounds 1 and 2 prevented or reduced EEG effects, such as increased amplitude of total spectra and high-voltage spindle (HVS) activity as well. Furthermore, choline esters showed a noticeable effectiveness in reversing the EEG changes produced in rats by AMPA-induced lesion of NBM.

Seizure susceptibility to various convulsant stimuli in dystrophin-deficient mdx mice.

In the present study, the susceptibility of the mdx mouse, a dystrophin-deficient genetic model of Duchenne muscular dystrophy (DMD), to various convulsant stimuli has been evaluated and compared to three related mice strains (C57BL/6J, C57BL/10 and DBA/2 mice). Animals were treated with chemical convulsants impairing gamma-aminobutyric acid (GABA) neurotransmission [pentylenetetrazole, picrotoxin, bicuculline, methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM), methyl-beta-carboline-3-carboxylate (beta-CCM)], enhancing glutamatergic neurotransmission [N-methyl-d-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and kainic acid (KA)] or a K(+) channel blocker (4-aminopyridine). Occurrence of clonic and/or tonic seizures was evaluated to observe possible differences in seizure susceptibility.

Choline pivaloyl esters improve in rats cognitive and memory performances impaired by scopolamine treatment or lesions of the nucleus basalis of Meynert.

The effects of two choline pivaloyl esters, [2-(2,2-dimethylpropionyloxy)ethyl]trimethylammonium iodide (1) and [2-(2,2-dimethylpropionyloxy)ethyl]trimethylammonium 2,2-dimethylpropionate (2), on learning and memory impairments induced in rats by scopolamine or lesions of nucleus basalis magnocellularis (NBM) have been evaluated by object recognition and Morris water maze tests in comparison with Tacrine (THA). Both 1 and 2 restored discrimination in object recognition test for assessing working-episodic memory and improved spatial memory in scopolamine or NBM-lesioned rats as well. The positive effects produced by 1 and 2 on cognitive and memory deficits were well comparable with those evoked by THA, used as reference compound.