Basal levels of metabolic activity are elevated in Genetic Absence Epilepsy Rats from Strasbourg (GAERS): measurement of regional activity of cytochrome oxidase and lactate dehydrogenase by histochemistry

The Genetic Absence Epilepsy Rats from Strasbourg (GAERS) are considered an isomorphic, predictive, and homologous model of human generalized absence epilepsy. It is characterized by the expression of spike-and-wave discharges in the thalamus and cortex. In this strain, basal regional rates of cerebral glucose utilization measured by the quantitative autoradiographic [(14)C]2-deoxyglucose technique display a widespread consistent increase compared to a selected strain of genetically nonepileptic rats (NE). In order to verify whether these high rates of glucose metabolism are paralleled by elevated activities of the enzymes of the glycolytic and tricarboxylic acid cycle pathways, we measured by histochemistry the regional activity of the two key enzymes of glucose metabolism, lactate dehydrogenase (LDH) for the anaerobic pathway and cytochrome oxidase (CO) for the aerobic pathway coupled to oxidative phosphorylation. CO and LDH activities were significantly higher in GAERS than in NE rats in 24 and 28 of the 30 brain regions studied, respectively. The differences in CO and LDH activity between both strains were widespread, affected all brain systems studied, and ranged from 12 to 63%. The data of the present study confirm the generalized increase in cerebral glucose metabolism in GAERS, occurring both at the glycolytic and at the oxidative step. However, they still do not allow us to understand why the ubiquitous mutation(s) generates spike-and-wave discharges only in the thalamocortical circuit.     

Role of TNF-alpha receptors in mice intoxicated with the parkinsonian toxin MPTP

Local application of GABA-potentiating agents can prevent or reduce the development and maintenance of behavioral seizures induced by limbic kindling in rats. Microinjection and lesion studies suggest that the transition zone between anterior and posterior piriform cortex (PC), termed here central PC, is a potential target for transplantation of GABA-producing cells. In the present study, we transplanted conditionally immortalized mouse cortical neurons, engineered with the GABA-synthesizing enzyme GAD(65), to the central PC of rats. Suspensions of 1.5 x 10(5) cells in 1 microl were transplanted bilaterally. Control animals received transplantation of beta-galactosidase (beta-gal)-expressing cells. All rats were subsequently kindled through a chronically implanted electrode placed in the basolateral amygdala. The pre- and postkindling threshold currents for eliciting behavioral seizures were determined before and after kindling. We found the prekindling partial seizure threshold to be significantly increased by about 200% in the rats that received the GABA-producing cells compared to rats receiving beta-gal-producing transplants. After kindling, the seizure threshold tended to be higher by 100% in rats that received GABA-producing cells, although the difference from controls was not statistically significant. GABA-producing transplants had no significant effect on the rate of amygdala kindling, but the latency to the first generalized seizure during kindling was significantly increased in animals receiving GABA-producing cells. The transplanted cells showed long-term GAD(65) expression as verified immunohistologically after termination of the experiments. The findings substantiate and extend previous findings that the central PC is part of the anatomical substrate that facilitates propagation from partial to generalized seizures. The data demonstrate that genetically engineered cells have the potential to raise seizure thresholds when transplanted to the central PC.     

Prevalence and denial of sexual abuse in a male psychiatric inpatient population

While the link between sexual abuse and psychiatric morbidity is well established, there are only a few studies that have investigated the prevalence of sexual abuse in male psychiatric populations and these studies have typically employed designs that ignore methodological issues specific to male sexual abuse. The present study aims to contribute to this research using as methodologically sound approach as possible. Seventy-four male inpatients were interviewed using a questionnaire (J. N. Briere, 1992) about childhood sexual experiences. Approximately one third reported incidents that met this study's criteria for sexual abuse. Many of these men did not label such experiences as "sexual abuse." The results suggest that mental health professionals need to be aware that many of their male patients may have a history of sexual abuse and that potential minimization or denial of it is a barrier to disclosure.     

Effect of distance feedback on pacing strategy and perceived exertion during cycling

PURPOSE: The aim of this study was to investigate whether providing incorrect distance feedback would alter pacing strategies, perceived exertion, and heart rate during 20-km cycling time trials (TT). METHODS: Well-trained cyclists (N=15) performed a peak power output (PPO) test, familiarization trial, and four 20-km cycling TT during which they were provided with only distance feedback using 1-km distance splits. For the control trial, subjects received accurate feedback at each kilometer split. In the increase trial, they received inaccurate feedback at 0.775 km for the first kilometer split with the distance increasing by 25 m each subsequent split up to 1.25 km in the final kilometer split. For the decrease trial, inaccurate feedback was provided at 1.25 km for the first kilometer split with the distance decreasing by 25 m each subsequent split up to 0.775 km in the final split. For the random trial, distance splits were randomized. RESULTS: No significant differences were found in the finishing times between trials. Pacing strategies were unaltered as suggested by similar power output profiles during all trials. RPE scores were also similar for all trials. However, average heart rate varied significantly between trials (P<0.05). CONCLUSIONS: These results suggest that exercise performance, pacing strategy, and RPE during a 20-km cycling TT are not altered by incorrect distance feedback. The data supported the existence of a pacing strategy that is set before exercise and that is unaffected by external distance feedback.     

Postnatal maturation of cytochrome oxidase and lactate dehydrogenase activity and age-dependent consequences of lithium-pilocarpine status epilepticus in the rat: a regional histoenzymology study

The lithium-pilocarpine (Li-Pilo) model of epilepsy reproduces some pathophysiological, temporal, and developmental features of human temporal lobe epilepsy. In this model, rates of cerebral glucose utilization measured by the [(14)C]2-deoxyglucose technique increased during the initial status epilepticus (SE) and decreased during the latent or chronic periods. To correlate these metabolic changes with the activities of the enzymes of the glycolytic and tricarboxylic acid cycle pathways, we measured by histoenzymology the regional activity of two key enzymes of glucose metabolism, lactate dehydrogenase (LDH) for the anaerobic pathway and cytochrome oxidase (CO) for the aerobic pathway coupled to oxidative phosphorylation, at various times after SE induced by Li-Pilo in 10- (P10), 21-d-old (P21) and adult rats for CO and in adult rats only for LDH. CO activity was slightly affected in P10 and P21 rats only at 4 and 24 h and normalized by 14 d after SE. In adult rats, CO activity decreased at 4 and 24 h in damaged areas, like entorhinal cortex, hippocampal CA3 area, amygdala, and thalamus. At 14 d after SE, CO activity was decreased only in entorhinal cortex and increased in brainstem regions involved in the remote control of seizures. In adult rats, LDH activity decreased at 24 h and 14 d after SE in sensorimotor and entorhinal cortex. These data show that the enzymatic equipment underlying the metabolism of glucose is not severely affected by Li-Pilo SE and confirm our previous observations concerning the relative metabolic hyperactivity of brain regions involved in the seizure circuit despite marked neuronal loss.     

A simple method for short-term controlled anesthesia in newborn mice

In this study, we describe a simple and inexpensive method for inducing short-term anesthesia and rapid recovery in newborn mice. Litters of Swiss mice pups were randomly allocated to testing on postnatal days 2, 5, and 8. Anesthesia was induced by placing the pup in a syringe and adding a volume of isoflurane-saturated gas that produced an estimated level of 32% isoflurane. Exposure to isoflurane lasted 30 s. All the pups survived the anesthesia. At all study ages, this method abolished the nociceptive response to tail clamp without inducing mortality, thus showing effective anesthesia. Recovery from anesthesia was assessed immediately after isoflurane exposure, based on two nonnoxious behavioral tests: the defensive response to a drop of water (10 tests, 1 min apart) and 10 min later the righting reflex, i.e., the time to recovery of the prone position (five tests, 10 min apart). The water drop test scores increased during the recovery phase toward the control values in all age groups. Treatment and time had no significant effect on righting reflex scores. The initial volume in the syringe, the volume of added isoflurane-saturated gas, and the duration of exposure may be adjusted according to postnatal age and specific strains or species (e.g., rats). This method is well suited to behavioral or physiological phenotype studies in developing mice, in which noxious procedures must precede functional testing, making rapid recovery from anesthesia a key requirement.