Antonio Mendonça

Maintenance on L-deprenyl prolongs life in aged male rats

The effect of l-deprenyl on longevity was examined in male Fischer rats. Subcutaneous injections of either l-deprenyl (0.25 mg/kg) or saline were given every other day starting at 23 to 25 months of age. The deprenyl-treated animals showed a significant increase in both mean and maximum survival. The differences were largest in the longest surviving animals, suggesting that an earlier onset for treatment may be beneficial. Analysis of body weights ruled out deprenyl-induced dietary restriction as an explanation for the group differences in survival. To the contrary, after about four months of treatment, the animals of l-deprenyl showed a slower rate of decrease in body weight than the controls.

Steroid hormones affect limbic afterdischarge thresholds and kindling rates in adult female rats.

UNLABELLED Catamenial epileptics show particular vulnerability to seizures during menstruation and at the time of ovulation, when circulating estradiol (E(2))/progesterone (P(4)) ratios are high. The present study tested the hypothesis that alterations in neuronal excitability induced by E(2) and P(4) affect thresholds and the development of secondary generalization in kindled rats. METHODS The effects of endogenous hormones secreted during the estrous cycle, and of exogenous exposure to E(2) and P(4) after ovariectomy (OVX), with and without adrenalectomy (ADX), were tested. Kindling electrodes were implanted in the basolateral amygdala or dorsal hippocampus in adult female rats. The anticonvulsive effects of P(4) on amygdala kindled seizures were also determined in intact subjects. RESULTS In intact females, afterdischarge thresholds (ADTs) in the amygdala were significantly lower (306+/-48 microA; peak to peak) at mid-day proestrus, just prior to ovulation, when serum E(2) is elevated. ADTs were more than twofold higher (808+/-95 microA) during metestrus, coincident with peak ovarian P(4) secretion. In OVX females, amygdala thresholds were lowest with E(2) replacement and highest with P(4) replacement. Hippocampal ADT was unaffected by hormone replacement after OVX. The rates of both amygdala and hippocampal kindling were significantly accelerated by E(2) and slowed by P(4). E(2) replacement significantly increased serum corticosterone (CORT) levels. In ADX rats, CORT replacement increased kindling rates, synergizing with the effects of E(2). In fully kindled animals, P(4) administration suppressed motor seizures in approximately 60% of cases. CONCLUSIONS E(2) lowers amygdala ADTs and facilitates kindling. This effect may involve both direct E(2) effects and indirect effects mediated via increased levels of circulating corticosterone. P(4) raises amygdala ADTs, slows kindling development and suppresses fully kindled seizures. Hence, P(4) may have potential therapeutic value for women with catamenial epilepsy.

Dietary fat, ketosis, and Seizure resistance in rats on the ketogenic diet

Summary: Purpose: Fat is the major component of the ketogenic diet (KD), yet no studies have examined whether the type of fat used in the diet can be optimized to provide additional benefits. The purpose of the present experiments was to compare the efficiency of different fats in inducing ketosis and affording seizure resistance.

The MCT Ketogenic Diet: Effects on Animal Seizure Models

Male Wistar rat pups were weaned at 20 days of age and placed on either a control diet or a ketogenic diet containing medium-chain triglyceride (MCT) oil. After 10 days on the diets, they were subjected to one of four seizure tests-maximal electric shock, threshold electroconvulsive shock, threshold pentylenetetrazol, or maximal pentylenetetrazol. After testing, subjects were sacrificed and blood samples were analyzed for beta-hydroxybutyrate concentration. It was found that the MCT diet produced blood levels of beta-hydroxybutyrate that were comparable to or higher than those commonly reported in clinical studies. However, no anticonvulsant effects were seen in any of the seizure tests. In fact, the tests involving maximal seizures actually showed proconvulsant effects. It appears that clinical levels of ketones may be present in the bloodstream without suppressing seizures.

EEG rhythms of the sensorimotor region during hand movements

The aim of this study was to determine what motor behaviors or conditions were associated with an increased occurrence of beta activity in the sensorimotor region of human subjects. EEG recordings were obtained from 8 electrodes symmetrically arranged around C3, with 3 cm interelectrode spacing. The electrode montage allowed calculation of the Laplacian operator at two positions, C3r and C3c, overlying the hand area of the motor cortex and of the somatosensory cortex, respectively. A variety of tasks involving right-hand movements of different levels of complexity, attention and preparation were performed. The corresponding EEG power spectra were subsequently computed for frequencies between 7 and 50 Hz. Repetitive hand movements alone (either drawing circles or writing ones signature) did not result in significantly increased beta activity in the sensorimotor region compared to relaxed conditions. However, both motor preparations and focused attention, whether movements were performed or not, were associated with an increase of high frequency beta activity (30-50 Hz) in the sensorimotor region. Therefore, the facilitatory effect of attention and motor preparation and not the functional activation of the sensorimotor cortex by hand movements was associated with an increase in synchronized fast beta activity.

Amygdala-kindled and electroconvulsive seizures alter hippocampal expression of the m1 and m3 muscarinic cholinergic receptor genes

Expression of m1 and m3 muscarinic cholinergic receptors mRNAs was examined in rat hippocampus following either: (1) kindling to five Stage 5 amygdala-kindled seizures; or (2) eight electroconvulsive shock (ECS) seizures. Twenty-four hours after the last seizure of either type, there was a significant decrease in both m1 and m3 mRNAs in CA1, CA3 and the dentate gyrus subfields of the hippocampus. Twenty-eight days after the last seizure of either type, there was a significant increase in m1 mRNAs in CA1, CA3, and the dentate gyrus; for m3 mRNAs, there was a significant increase in CA3 28 days after the last ECS seizure, and in CA1 and CA3 28 days after the last kindled seizure. These results suggest that seizures alter the cholinergic system in the hippocampus, and that some of the alterations are very long-lasting.

Kindling induces an asymmetric enhancement of N-type Ca2+ channel density in the dendritic fields of the rat hippocampus

The mechanisms underlying epilepsy are largely unknown. Recent genetic, pharmacological and electrophysiological data indicate a significant, but poorly understood, role for voltage-dependent calcium channels (VDCCs). Since the contribution of ion channels to nerve function depends on their cell surface distribution, we hypothesized that epilepsy might alter VDCC surface densities. To test this idea we mapped the expression and distribution of fluorescent-labeled hippocampal N-type VDCCs (N-VDCCs) in an animal model of epilepsy, amygdala kindling. Image analysis demonstrated that kindling induced a 21-40% increase in N-VDCC expression in CA1 but not CA3. This increase occurred in the stratum radiatum and was twice as high in tissues contra- versus ipsi-lateral to the stimulating electrode. These data rationalize recent electrophysiology and argue that a persistent alteration in N-VDCC trafficking in dendrites or nerve termini may contribute to seizure-induced synaptic plasticity.

Spatially modulated touch responses in parietal cortex

Cortical neurons with low-threshold, cutaneous receptive fields on the fingers were recorded in areas 5 and 7b of the parietal lobe in two awake monkeys, trained in a visually guided reach task. 72% (81/113) of the cells responded when targets displayed on a videomonitor were actively touched. Of these, 20 neurons discharged preferentially when target contact was made on one side of the screen compared with the other. This spatial modulation of the cutaneous modality may have originated in neighboring joint-related neurons which were directionally selective.