Neonatal status epilepticus alters prefrontal–striatal circuitry and enhances methamphetamine-induced behavioral sensitization in adolescence

Lin, Tzu Chao; Huang, Li; Huang, Ya‐Fang; Chen, Gunng Shinng

doi:10.1016/j.yebeh.2008.12.005

Cited by 17 publications

(8 citation statements)

References 78 publications

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“…This effect could be related to decreased motivation, increased emotionality or impaired social memory. Lin et al (2009) reported in lithium-pilocarpine-induced neonatal seizures reduced levels of dopamine in the PFC. It is well-established that the dopamine found in the PFC originates from the ventral tegmental area, a structure involved in neural network of social behaviors (Goodson and Kabelik, 2009) is also involved in and emotional responses (Baskerville and Douglas, 2010).…”

Section: Discussionmentioning

confidence: 99%

Altered anxiety-related and abnormal social behaviors in rats exposed to early life seizures

Castelhano¹,

Cassane²,

Scorza³

et al. 2013

Front. Behav. Neurosci.

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Neonatal seizures are the most common manifestation of neurological dysfunction in the neonate. The prognosis of neonatal seizures is highly variable, and the controversy remains whether the severity, duration, or frequency of seizures may contribute to brain damage independently of its etiology. Animal data indicates that seizures during development are associated with a high probability of long-term adverse effects such as learning and memory impairment, behavioral changes and even epilepsy, which is strongly age dependent, as well as the severity, duration, and frequency of seizures. In preliminary studies, we demonstrated that adolescent male rats exposed to one-single neonatal status epilepticus (SE) episode showed social behavior impairment, and we proposed the model as relevant for studies of developmental disorders. Based on these facts, the goal of this study was to verify the existence of a persistent deficit and if the anxiety-related behavior could be associated with that impairment. To do so, male Wistar rats at 9 days postnatal were submitted to a single episode of SE by pilocarpine injection (380 mg/kg, i.p.) and control animals received saline (0.9%, 0.1 mL/10 g). It was possible to demonstrate that in adulthood, animals exposed to neonatal SE displayed low preference for social novelty, anxiety-related behavior, and increased stereotyped behavior in anxiogenic environment with no locomotor activity changes. On the balance, these data suggests that neonatal SE in rodents leads to altered anxiety-related and abnormal social behaviors.

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Section: Discussionmentioning

confidence: 99%

Altered anxiety-related and abnormal social behaviors in rats exposed to early life seizures

Castelhano¹,

Cassane²,

Scorza³

et al. 2013

Front. Behav. Neurosci.

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“…Rapid kindling leads to an increase of Rgs4 mRNA in hippocampus and forebrain, but not in brainstem or cerebellum [23]. Rgs4 expression is downregulated in prefrontal cortex and striatum by neonatal status epilepticus [24]. In rat adrenal glands, Rgs4 is upregulated by aldosterone secretagogues, both in vivo and in vitro [25].…”

Section: Introductionmentioning

confidence: 99%

MEKK1-MKK4-JNK-AP1 Pathway Negatively Regulates Rgs4 Expression in Colonic Smooth Muscle Cells

Zhang

Liu

et al. 2012

PLoS ONE

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Background Regulator of G-protein Signaling 4 (RGS4) plays an important role in regulating smooth muscle contraction, cardiac development, neural plasticity and psychiatric disorder. However, the underlying regulatory mechanisms remain elusive. Our recent studies have shown that upregulation of Rgs4 by interleukin (IL)-1β is mediated by the activation of NFκB signaling and modulated by extracellular signal-regulated kinases, p38 mitogen-activated protein kinase, and phosphoinositide-3 kinase. Here we investigate the effect of the c-Jun N-terminal kinase (JNK) pathway on Rgs4 expression in rabbit colonic smooth muscle cells.Methodology/Principal FindingsCultured cells at first passage were treated with or without IL-1β (10 ng/ml) in the presence or absence of the selective JNK inhibitor (SP600125) or JNK small hairpin RNA (shRNA). The expression levels of Rgs4 mRNA and protein were determined by real-time RT-PCR and Western blot respectively. SP600125 or JNK shRNA increased Rgs4 expression in the absence or presence of IL-1β stimulation. Overexpression of MEKK1, the key upstream kinase of JNK, inhibited Rgs4 expression, which was reversed by co-expression of JNK shRNA or dominant-negative mutants for MKK4 or JNK. Both constitutive and inducible upregulation of Rgs4 expression by SP600125 was significantly inhibited by pretreatment with the transcription inhibitor, actinomycin D. Dual reporter assay showed that pretreatment with SP600125 sensitized the promoter activity of Rgs4 in response to IL-1β. Mutation of the AP1-binding site within Rgs4 promoter increased the promoter activity. Western blot analysis confirmed that IL-1β treatment increased the phosphorylation of JNK, ATF-2 and c-Jun. Gel shift and chromatin immunoprecipitation assays validated that IL-1β increased the in vitro and ex vivo binding activities of AP1 within rabbit Rgs4 promoter.Conclusion/SignificanceActivation of MEKK1-MKK4-JNK-AP1 signal pathway plays a tonic inhibitory role in regulating Rgs4 transcription in rabbit colonic smooth muscle cells. This negative regulation may aid in maintaining the transient level of RGS4 expression.

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“…There is some evidence that ELS can affect the PFC in a rodent model. Specifically, neonatal status epilepticus can modify later dopaminergic and glutamatergic neurochemistry in the PFC, and alter behaviors related to addiction [23]. However, it is unknown whether repeated ELS affect PFC cellular architecture and behavioral functions that are typically associated with this structure.…”

Section: Introductionmentioning

confidence: 99%

Early-life seizures produce lasting alterations in the structure and function of the prefrontal cortex

Kleen¹,

Sesqué²,

Wu³

et al. 2011

Epilepsy & Behavior

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Early-life seizures (ELS) are associated with long-term behavioral disorders including autism and ADHD, suggesting that frontal lobe structures may be permanently affected. We tested whether ELS produce structural alterations in the prefrontal cortex (PFC) and impair PFC-mediated function using an operant task of behavioral flexibility in rats. Adult rats that had been exposed to 75 flurothyl seizures during postnatal days 1–10 showed decreased behavioral flexibility in the task compared to controls over multiple behavioral sessions, measured as a lever preference asymmetry (p<0.001) and a decreased efficiency of attaining food rewards (p<0.05). ELS rats also showed an increased thickness of the PFC (p<0.01), primarily attributed to layer V (p<0.01) with no differences in cell density. These structural changes correlated with lever preference behavioral impairments (p<0.05). This study demonstrates that the consequences of ELS extend to the PFC, which may help explain the high prevalence of comorbid behavioral disorders following ELS.

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Neonatal status epilepticus alters prefrontal–striatal circuitry and enhances methamphetamine-induced behavioral sensitization in adolescence

Cited by 17 publications

References 78 publications

Altered anxiety-related and abnormal social behaviors in rats exposed to early life seizures

Altered anxiety-related and abnormal social behaviors in rats exposed to early life seizures

MEKK1-MKK4-JNK-AP1 Pathway Negatively Regulates Rgs4 Expression in Colonic Smooth Muscle Cells

Early-life seizures produce lasting alterations in the structure and function of the prefrontal cortex

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