neuropeptide-y and Seizures--Febrile

Seizures induce profound plastic changes in the brain, including altered expression of neuropeptide Y (NPY) and its receptors. Here, I discuss a potential role of NPY plasticity in the developmental brain: in a rat model of febrile seizures (FS), the most common type of seizures in infants and young children, NPY expression was up-regulated in hippocampus after experimentally induced FS. Interestingly, NPY up-regulation was associated with an increased seizure threshold for additional (recurrent) FS, and this effect was abolished when an antagonist against NPY receptor type 2 was applied. These findings suggest that inhibitory actions of NPY, released after seizures, exert a protective effect that reduces the risk of seizure recurrence in the developing brain.

Topics: Animals; Disease Models, Animal; Humans; Neuropeptide Y; Rats; Recurrence; Seizures, Febrile

It has been reported that prenatal undernutrition affects the development of the peripheral immune system. In this study, the effects of prenatal undernutrition on the febrile response and hypothalamic innate immune system were evaluated in male rats. Pregnant rats were divided into normally nourished (NN) and undernourished groups (UN). The febrile and anorectic responses to lipopolysaccharides (LPS) were evaluated in the offspring of NN and UN dams. The hypothalamic expression levels of pro-inflammatory cytokines, toll-like receptor 4 (TLR4), and neuropeptide Y (NPY) were also evaluated. The UN rats exhibited significantly lighter body weights than the NN rats at birth; however, their mean body weight was the same as that of the NN rats by postnatal day 10. In adulthood, the UN rats exhibited significantly stronger febrile responses than the NN rats, and the anorectic responses of the UN rats also tended to be stronger than those of the NN rats. On the other hand, no differences in hypothalamic interleukin (IL)-1β, IL-6, tumor necrosis factor-α, TLR4, or NPY mRNA expression were detected between the NN and UN rats. These results suggest that prenatal undernutrition has long-lasting effects on the febrile response to LPS. However, the precise mechanism underlying these effects and their pathophysiological significance remain unclear.

Topics: Analysis of Variance; Animals; Body Temperature; Body Weight; Cytokines; Eating; Female; Glyceraldehyde-3-Phosphate Dehydrogenases; Hypothalamus; Lipopolysaccharides; Male; Malnutrition; Neuropeptide Y; Peptide Fragments; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley; RNA, Messenger; Seizures, Febrile; Time Factors; Toll-Like Receptor 4

It is known that neuropeptide Y which is widely distributed throughout the central nervous system is able to prevent seizures in animals. There are limited studies about the role of neuropeptide Y in febrile seizures. This study was conducted to evaluate the association between plasma neuropeptide Y level and febrile seizures in children. Seventy six patients with typical and atypical febrile seizures (each group 38 patients) and 38 sex and age matched control subjects were enrolled. The mean plasma levels of neuropeptide Y in typical and atypical febrile seizures were 90.60±28.01 and 97.34±41.27 pmol/l respectively. This value in control group was 88.94±32.66 pmol/l. There was no significant differences between groups regarding plasma neuropeptide Y level (P=0.532). Also, there was no significant difference in comparison with case groups (P=0.40). This study revealed that there is no association between plasma neuropeptide Y and febrile seizures.

Topics: Age Factors; Case-Control Studies; Child, Preschool; Female; Humans; Infant; Iran; Male; Neuropeptide Y; Prospective Studies; Risk Factors; Seizures, Febrile

Febrile convulsion (FC) is the most common neurological disease in children. Cases with seizures that persist for more than 15 minutes or recurrent seizures within the same febrile illness are considered to be atypical and may have a different prognosis. Neuropeptide Y (NPY), an endogenous anticonvulsant that is widely distributed throughout the central nervous system, including the hippocampus, is known to prevent seizures by increasing the seizure threshold. Based on our previously finding that patients with atypical FC have lower concentrations of NPY, we hypothesized that the concentration of NPY may play a role in the development of atypical FC. To investigate this hypothesis, we used a radioimmunoassay to measure the plasma NPY concentration of 60 children with FC (typical FC, n = 46; atypical FC, n = 14) and 56 age-matched controls. The atypical FC group had significantly lower concentrations of NPY than children with typical FC and controls (66.47 +/- 19.11 pmol/L vs. 88.68 +/- 28.50 pmol/L and 86.82 +/- 22.66 pmol/L, respectively). Very low NPY levels were found in two patients; one patient (NPY level: 44.75 pmol/L) experienced prolonged seizures lasting for up to 1 hour and the other had recurrent seizures (three seizures) during the same febrile illness (NPY level: 33.53 pmol/L). These results suggest that patients with inadequate NPY inhibitory activity are more susceptible to atypical FC.

Topics: Adolescent; Adult; Case-Control Studies; Child; Female; Humans; Male; Neuropeptide Y; Radioimmunoassay; Seizures, Febrile; Young Adult

Neuropeptide Y (NPY) has been shown to depress the hyperexcitability of neurons. In the present study, we investigated the association between the nucleotide (nt) 5671 C/T polymorphism of the NPY gene and the plasma NPY level in patients with febrile seizures (FS). Fifty-six patients with FS and 55 control subjects were enrolled. Genotype and allele frequencies were compared. The frequencies of genotypes TT, TC and CC for the NPY gene nt 5671 C/T polymorphism were 21.4%, 28.6% and 50.0%, respectively, in patients with FS, and 14.6%, 40.0% and 45.4%, respectively, in control subjects. The frequencies of alleles T and C were 35.7% and 64.3%, respectively, in patients with FS, while those in the control group were 34.5% and 65.5%, respectively. We found no significant relationship between the NPY gene nt 5671 C/T polymorphism and FS. The plasma NPY concentrations of the FS group, the age-matched non-FS group, and subjects aged > 6 years in the non-FS group were 48.23 +/- 32.49, 55.36 +/- 23.12, and 70.10 +/- 60.31 pg/mL, respectively. These results indicate no statistical difference in plasma NPY concentration between FS patients and the non-FS group. However, plasma NPY concentration was found to increase significantly with age.

Topics: Child, Preschool; Female; Humans; Infant; Male; Neuropeptide Y; Polymorphism, Genetic; Seizures, Febrile

Febrile seizures (FSs) typically occur at the onset of fever and do not recur within the same febrile episode despite enduring or increased hyperthermia. Recurrent seizures during the same febrile episode are considered "complex," with potentially altered prognosis. A characterized immature rat model of FS was used to test the hypotheses that (1) a first FS influences the threshold temperature for subsequent ones, and (2) the underlying mechanisms involve the release and actions of the endogenous inhibitory hippocampal neuropeptide Y (NPY). Experimental FSs were induced two or three times, at 3- to 4-h intervals, and threshold temperatures measured. To determine the potential effects of seizure-induced endogenous NPY on thresholds for subsequent seizures, an antagonist of the major hippocampal NPY receptor (type 2) was infused prior to induction of the second seizure. As an indicator of NPY release, NPY expression was determined 4 and 24 h later. Threshold core and brain temperatures for hyperthermic seizures were consistent with those observed during human fever. Threshold temperatures for a second and third seizure were significantly and progressively higher than those required for the first. This "protective" effect involved induction of endogenous NPY because it was abolished by the NPY antagonist. In addition, NPY mRNA expression was increased in dentate gyrus, CA3 and CA1, after an experimental FS, consistent with peptide release. Collectively these data indicate that the absence of repetitive seizures during a febrile episode involves the inhibitory actions of endogenous NPY, suggesting that the signaling cascade triggered by this peptide might provide targets for therapeutic intervention.

Topics: Age Factors; Animals; Body Temperature; Disease Models, Animal; Fever; Hippocampus; Neuropeptide Y; Rats; Rats, Sprague-Dawley; Receptors, Neuropeptide Y; Recurrence; Seizures, Febrile