Effects of early‐life LiCl‐Pilocarpine‐induced status epilepticus on memory and anxiety in adult rats are associated with mossy fiber sprouting and elevated CSF S100B protein

Abstract

SUMMARYPurpose: This study investigated putative correlations among behavioral changes and: (1) neuronal loss, (2) hippocampal mossy fiber sprouting, and (3) reactive astrogliosis in adult rats submitted to early-life LiCl-pilocarpine-induced status epilepticus (SE). Methods: Rats (P15) received LiCl (3 mEq/kg, i.p.) 12-18 h prior pilocarpine (60 mg/kg; s.c.). At adulthood, animals were submitted to behavioral tasks and after the completion of tasks biochemical and histological analysis were performed. Results: In SE group, it was observed an increased number of degenerating neurons in the CA1 subfield and in the hilus of animals 24 h after SE. At adulthood, SE group presented an aversive memory deficit in an inhibitory avoidance task and the animals that presented lower latency to the step down showed a higher score for mossy fiber sprouting. In the light-dark exploration task, SE rats returned less and spent less time in the light compartment and present an increased number of risk assessment behavior (RA). There was a negative correlation between the time spent in the light compartment and the score for mossy fiber sprouting and a positive correlation between score for mossy fiber sprouting and number of RA. LiClpilocarpine-treated animals showed higher levels of S100B immunocontent in the CSF as well as a positive correlation between the score for sprouting and the GFAP immunocontent in the CA1 subfield, suggesting an astrocytic response to neuronal injury. Conclusions: We showed that LiCl-pilocarpineinduced SE during development produced longlasting behavioral abnormalities, which might be associated with mossy fiber sprouting and elevated CSF S100B levels at adulthood. KEY WORDS: Status epilepticus, Development, Learning and memory, Anxiety, S100B protein, Mossy fiber sprouting.Epilepsy is a common neurological disorder that affects children much more often than adults (Cowan, 2002). There is a clinical debate about brain damage and behavioral impairment induced by epileptic activity in infants

Low‐intensity physical training recovers object recognition memory impairment in rats after early‐life induced Status epilepticus

“…Two hours after SE onset, animals cycled through periods of forelimb clonus and periods of loss of the righting reflex with falling. All behavioural manifestations reported here for convulsive SE are in agreement with previous descriptions from Hirsch et al (1992) and de Oliveira et al (2008).…”

“…Neurological disabilities observed in humans are very similar to those found in animal models of SE. Male rats that suffered SE at 16–20 days old showed long‐term deficits in spatial learning in the water maze task (Cilio et al, 2003) and showed an impairment in aversive memory learning in an inhibitory avoidance task (de Oliveira et al, 2008). Furthermore, animals submitted to LiCl‐pilocarpine‐induced SE between the 2nd and 3rd weeks of life presented increased levels of anxiety in the elevated plus maze, as well as impaired performance in the water maze task 3 months after the insult (Kubová et al, 2004).…”

Oral Uncaria rhynchophylla (UR) reduces kainic acid-induced epileptic seizures and neuronal death accompanied by attenuating glial cell proliferation and S100B proteins in rats

“…The overexpression of S100B protein is highly dependent on environmental factors including harmful stimuli. The overexpression of S100B protein during the epileptic process (especially in chronic epilepsy) suggests a principle role of S100B (Sakatani et al, 2007;de Oliveira et al, 2008). In the current study, we showed that S100B protein was increased with KA-induced epilepsy and this phenomenon was reversed by oral UR.…”

Hippocampal Y2 receptor-mediated mossy fiber plasticity is implicated in nicotine abstinence-related social anxiety-like behavior in an outbred rat model of the novelty-seeking phenotype

“…Although the direct link between hippocampal MF plasticity and anxiety-like behavior has not been reported, studies have shown a positive correlation between SP-MF sprouting and increased anxiety-like behavior in inbred (Prior et al ., 1997), as well as in outbred rats (de Oliveira et al ., 2008; Oztan et al ., 2011), suggesting that the MF system may contribute to modulation of anxiety-like responses. In support of this premise, our present data show that increased social anxiety-like behavior observed in HRs following a behaviorally sensitizing nicotine regimen is accompanied by increased SP-MF terminal field size, in comparison to saline pre-trained controls.…”

“…Moreover, data from inbred mice correlate heritable variance in MF size with different emotional behaviors, such as fear conditioning and anxiety-like behavior (Prior et al ., 1997). Likewise, studies on outbred rats show a positive correlation between MF sprouting and anxiety-like behavior in the light-dark box test (de Oliveira et al ., 2008), implicating MF plasticity in regulation of anxiety.…”