Anticonvulsant and Antiepileptogenic Effects Mediated by Adeno-Associated Virus Vector Neuropeptide Y Expression in the Rat Hippocampus

Richichi, Cristina; Lin, En Ju; Stefanin, Daniela; Colella, Daniele; Ravizza, Teresa; Grignaschi, Giuliano; Veglianese, Pietro; Sperk, Günther; During, Matthew J.; Vezzani, Annamaria

doi:10.1523/jneurosci.4056-03.2004

Cited by 212 publications

(184 citation statements)

References 58 publications

Supporting

Mentioning

170

Contrasting

Unclassified

Order By: Relevance

“…Accordingly, increased NPY expression in the hippocampus after prenatal betamethasone exposure is congruent with anti-anxiety effects. Increased expression of NPY (which also has anticonvulsant features; Richichi et al, 2004) in the hippocampus may also help in explaining the slower dentate gyrus kindling rate in betamethasone-exposed immature rats compared to saline-exposed rats in our previous study (Velíšek, 2005b). Earlier studies have shown that mainly ventral but also dorsal hippocampus is involved in anxiety control (Andrews et al, 1997;Bannerman et al, 2002aBannerman et al, , b, 2003Gonzalez et al, 1998;Kjelstrup et al, 2002;McHugh et al, 2004) and NPY alterations in the hippocampus affect anxiety behaviors (Heilig, 2004;Thorsell et al, 2000).…”

Section: Technical Considerationsmentioning

confidence: 62%

Prenatal Exposure to Betamethasone Decreases Anxiety in Developing Rats: Hippocampal Neuropeptide Y as a Target Molecule

Velı́šek

2006

Neuropsychopharmacol

View full text Add to dashboard Cite

Repeated antenatal administration of betamethasone is frequently used as a life-saving treatment in obstetrics. However, limited information is available about the outcome of this therapy in children. The initial prospective studies indicate that there are behavioral impairments in children exposed to repeated courses of prenatal betamethasone during the third trimester of pregnancy. In this study, pregnant rats received two betamethasone injections on day 15 of gestation. Using immunohistochemistry, the expression of a powerful anxiolytic molecule neuropeptide Y (NPY) was determined on postnatal day (PN) 20 in the hippocampus and basolateral amygdala (structures related to anxiety and fear) of the offspring. Prenatal betamethasone exposure induced significant increases in NPY expression in the hippocampus but not in the amygdala. Indeed, behavioral tests in the offspring, between PN20 and PN22 in the open field, on the horizontal bar, and in the elevated plus maze, indicated decreases in anxiety, without impairments in motor performance or total activity. Decreased body weight in betamethasone-exposed rats confirmed long-lasting effects of prenatal exposure. Thus, prenatal betamethasone treatment consistently increases hippocampal NPY, with decreases in anxiety-related behaviors and hippocampal role in anxiety in rats. Animal models may assist in differentiation between pathways of the desired main effect of the antenatal corticosteroid treatment and pathways of unwanted side effects. This differentiation can lead to specific therapeutic interventions directed against the side effects without eliminating the beneficial main effect of the corticosteroid treatment.

show abstract

Section: Technical Considerationsmentioning

confidence: 62%

Prenatal Exposure to Betamethasone Decreases Anxiety in Developing Rats: Hippocampal Neuropeptide Y as a Target Molecule

Velı́šek

2006

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…Indeed NPY is an inhibitory neuromodulator, whose synthesis is prompted by seizures (Vezzani and Sperk, 2004), and is thus considered as part of an endogenous antiepileptic mechanism (Richichi et al, 2004). Accordingly, here NPY expression increased in the temporal cortex of naïve marmosets as a consequence of repetitive PTZ administration, inherent to the drug testing protocol.…”

Section: Discussionmentioning

confidence: 88%

Seizures triggered by pentylenetetrazol in marmosets made chronically epileptic with pilocarpine show greater refractoriness to treatment

et al. 2016

View full text Add to dashboard Cite

a b s t r a c tThe efficiency of most of the new antiepileptic drugs (AEDs) on clinical trials still falls short the success reported in pre-clinical studies, possibly because the validity of the animal models is insufficient to fully represent the human pathology. To improve the translational value for testing AEDs, we propose the use of non-human primates. Here, we suggest that triggering limbic seizures with low doses of PTZ in pilocarpine-treated marmosets might provide a more effective basis for the development of AED. Marmosets with epileptic background were more susceptible to seizures induced by PTZ, which were at least 3 times longer and more severe (about 6 times greater frequency of generalized seizures) in comparison to naïve peers. Accordingly, PTZ-induced seizures were remarkably less attenuated by AEDs in epileptic than naïve marmosets. While phenobarbital (40 mg/kg) virtually abolished seizures regardless of the animal's background, carbamazepine (120 mg/kg) and valproic acid (400 mg/kg) could not prevent PTZinduced seizures in epileptic animals with the same efficiency as observed in naïve peers. VPA was less effective regarding the duration of individual seizures in epileptic animals, as assessed in ECoG (p = 0.05). Similarly following CBZ treatment, the behavioral manifestation of generalized seizures lasted longer in epileptic (p < 0.05), which were also more frequent than in the naïve group (p < 0.05). As expected, epileptic marmosets experiencing stronger seizures showed more NPY-and FosB-immunostained neurons in a number of brain areas associated with the generation and spread of limbic seizures. Our results suggest that PTZ induced seizures over an already existing epileptic background constitutes a reliable and controllable mean for the screening of new AEDs.

show abstract

“…During (University of Auckland, Auckland, New Zealand). Production of rAAV-NPY has been described previously (During et al, 2003;Richichi et al, 2004). Per site, 1 l of virus (1 ϫ 10 8 genomic copies) was injected over 5 min, after which the needle was kept in place for 10 min before removal.…”

Section: Methodsmentioning

confidence: 99%

Differential Effects of Recombinant Adeno-Associated Virus-Mediated Neuropeptide Y Overexpression in the Hypothalamic Paraventricular Nucleus and Lateral Hypothalamus on Feeding Behavior

Tiesjema¹,

Adan²,

Luijendijk³

et al. 2007

J. Neurosci.

View full text Add to dashboard Cite

It is well known that neuropeptide Y (NPY) increases food intake. The hypothalamic paraventricular nucleus (PVN) and the lateral hypothalamus (LH) are both involved in the acute, hyperphagic effects of NPY. Although it is obvious that increased energy intake may lead to obesity, it is less understood which aspects of feeding behavior are affected and whether one or multiple neural sites mediate the effects of long-term increased NPY signaling. By long-term overexpressing NPY in either the PVN or the LH, we uncovered brain site-specific effects of NPY on meal frequency, meal size, and diurnal feeding patterns. In rats injected with adeno-associated virus-NPY in the PVN, increased food intake resulted from an increase in the amount of meals consumed, whereas in rats injected in the LH, increased food intake was attributable to increased meal size. Interestingly, food intake and body weight gain were only temporarily increased in PVN-injected rats, whereas in LH-injected rats hyperphagia and body weight gain remained for the entire 50 d. Moreover, in LH-NPY rats, but not in PVN-NPY rats, diurnal rhythmicity with regard to food intake and body core temperature was lost. These data clearly show that the NPY system differentially regulates energy intake and energy expenditure in the PVN and LH, which together adjust energy balance.

show abstract

Anticonvulsant and Antiepileptogenic Effects Mediated by Adeno-Associated Virus Vector Neuropeptide Y Expression in the Rat Hippocampus

Cited by 212 publications

References 58 publications

Prenatal Exposure to Betamethasone Decreases Anxiety in Developing Rats: Hippocampal Neuropeptide Y as a Target Molecule

Prenatal Exposure to Betamethasone Decreases Anxiety in Developing Rats: Hippocampal Neuropeptide Y as a Target Molecule

Seizures triggered by pentylenetetrazol in marmosets made chronically epileptic with pilocarpine show greater refractoriness to treatment

Differential Effects of Recombinant Adeno-Associated Virus-Mediated Neuropeptide Y Overexpression in the Hypothalamic Paraventricular Nucleus and Lateral Hypothalamus on Feeding Behavior

Contact Info

Product

Resources

About