This study aims to investigate the potential effects of anticonvulsant drugs on neuropeptides (galanin and neuropeptide Y) and neurotrophic factors (BDNF and NGF) in pentylenetetrazol (PTZ)-kindled seizures in the rat.
We subsequently studied to what extent CPON might affect seizure susceptibility and memory performance, respectively, to address two important questions to evaluate the potential of NPY gene therapy in epilepsy.
Viral overexpression of human NPY in the thalamus and somatosensory cortex in GAERS significantly reduced the time spent in seizure activity and number of seizures, whereas seizure duration was only reduced after thalamic NPY overexpression.
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.
NPY has recently gained much attention as an endogenous antiepileptic and antidepressant agent, as drugs with antiepileptic and/or mood-stabilizing properties may exert their action by increasing NPY concentrations, which in turn can reduce anxiety and depression levels, dampen seizures or increase seizure threshold.
Recent findings showed a long-lasting NPY over-expression in the rat hippocampus by local application of recombinant AAV vectors associated with reduced generalization of seizures, delayed kindling epileptogenesis, and strong reduction of chronic spontaneous seizures.
Several candidate genes such as neuropeptide Y and galanin have been demonstrated in preclinical studies to have a positive effect on seizure activity.
In a subset of APdE9 mice, seizure phenotype was associated with a loss of calbindin-D28k immunoreactivity in dentate granular cells and ectopic expression of neuropeptide Y in mossy fibers.
The present results in amygdala kindling and chemical seizure models suggest that NPY may play a more prominent role in determining seizure thresholds and severity of seizures than in events leading to epileptogenesis.
The present results in amygdala kindling and chemical seizure models suggest that NPY may play a more prominent role in determining seizure thresholds and severity of seizures than in events leading to epileptogenesis.
This concept is strongly supported by evidence that genetically modified rats overexpressing the NPY gene are less susceptible to seizures while deletion of NPY or Y2 receptor genes results in increased susceptibility to seizures.