Differential effects of aging on EEG after baclofen administration

Baclofen is a selective gamma-aminobutyric acid (GABA) type B agonist that may have important medicinal uses, such as in analgesics and drug addiction treatment. In addition, evidence is accumulating that suggests GABAergic-mediated neurotransmission is altered during aging. This study investigated whether baclofen administration (5 mg kg⁻¹) induces differential effects on cortical electrical activity with age. Electroencephalograms (EEGs) were recorded from young (3–4 months) and aged (15–17 months) rats, and both the absolute and relative powers in five frequency bands (delta: 2–4 Hz; theta: 4–8 Hz; alpha: 8–12 Hz; beta: 12–20 Hz; gamma: 20–100 Hz) were analyzed. Before administration of baclofen, we found that the EEG relative power in the beta band was higher in the aged than that in the young rats. After administration of baclofen, there was a slower increase in the relative power in the delta band in the aged than that in the young rats. Moreover, there was no significant difference between the two age groups in absolute power in any frequency band. These findings indicate that baclofen treatment appears to differentially modify cortical EEG activity as a function of age. Our data further elucidate the relationship between GABA_B receptor-mediated neurotransmission and aging.     

Cytological changes in hypophysis of immatur rats after administration of anti-LH antibodies (author's transl)]

In the present work, cytological changes produced in rats' pars distalis were studied by administration of anti-LH antibodies. The anti-LH sera was obtained by active immunization of adult rabbits using bovine LH hormone with Freund's complete adjuvant. Newborn albino Wistar male and female rats were daily and subcutaneously inoculated with 0.1 ml. to 0.8 ml of anti-LH sera from the first 24 hr. on during 5 weeks. For controls, a similar schedule of inoculations with normal rabbit serum was used. At weekly intervals during the treatment, 5 lots of rats were sacrificed and the rest after a recovery period of 95 days. At the end of the 2nd week of immunization, both male and female animals showed degranulated gonadotroph cells in the central part of the pars distalis; at the 3rd week these cells were hypertrophied and presented developed Golgi complex. At the 4th week, the first large vacuoles of "castration" were seen in the gonadotroph cells of male pars distalis, besides in the females the degranulation of gonadotrophs continued. During the last week of treatment, the gonadotrophs of the male animals presented a highly dilated Golgi complex, more "castration-like cells" and numerous mitosis figures. The gonadotrophs of females pars distalis presented degranulation, but not vacuoles. After the recovery period the gonadotrophs of male rats were similar to those of the control hypophisis and did not show castration vacuoles in their cytoplasm. In female rats, the gonadotrophic cells showed "castration-like vacuoles" and a raised number of mitosis cells compared to control pituitaries. The significance of these findings will be discussed.     

Mitochondria and dopamine: new insights into recessive parkinsonism

Recessively inherited mutations in parkin, DJ-1, and PINK1 have recently been linked to familial forms of parkinsonism. These syndromes are often clinically indistinguishable from Parkinson's disease, as similar neuronal groups, notably dopaminergic neurons, are selectively affected. Studies of the functions of these gene products may provide insights into the pathogenic mechanisms underlying the selective degeneration of dopaminergic neurons. Emerging evidence that one or several of these genes play important roles in mitochondrial function and the dopaminergic system suggests that these events may be early steps of the pathophysiological changes of the disease. This review will summarize recent advances in our understanding of these gene products, with emphasis on the surprising convergence of their functions.     

Changes in the EEG parameters related to parkinsonism and aging

The EEG parameters were analyzed in 73 patients with parkinsonism characterized by different levels of clinical disorders and duration of the disease (44- to 77-year-old persons, mean 58.1 years; group P) and in 60 practically healthy persons (control group, group C). Group C was divided into two subgroups: Cy and Co (persons younger and older than 40 years, respectively). In the P group, the powers of fluctuations in 1- and 2-ranges and of -waves in anterior recording sites, (F,C), was noticeably higher than those in the C group. These parameters were in positive correlation with the disease intensity; there was a trend toward a lower level of the above EEG components in older patients. Patients with a lower level of clinical symptoms showed lower power of -waves in posterior recording sites, (P,O), than that in the Co and, moreover, Cy subgroups. Yet, a higher level of clinical symptoms correlated with a higher level of this parameter. A decrease in the frequency of (F,C) and (P,O) components in the P group was found. These findings show that there are obvious shifts in spatial distribution, and relative levels and frequency parameters of brain electrical activity in parkinsonian patients, which reflects the multilevel pattern of brain disorders related to this disease.Neirofiziologiya/Neurophysiology, Vol. 27, No. 5/6, pp. 396–402, September–December, 1995.     

Dopamine antibodies in the pathogenesis of parkinsonism]

L-DOPA and dopamine (DA) binding antibodies were found in the blood serum of Parkinsonian patients and middle-aged and elderly normal persons. DA-binding serum gamma-globulins of parkinsonian patients injected into rat caudate nuclei induced the pathogenetic mechanism of Parkinson's syndrome (generator of pathologically enhanced excitation) in these brain part and evoked main parkinsonian symptoms (oligokinesia, rigidity, tremor). The serum gamma-globulins of Parkinsonian patients without Da-antibodies caused less pronounced EEG disturbances. Parkinsonian symptoms developed rarely and were shorter and less pronounced compared with the DA-antibody effect. The DA binding antibodies role in Parkinson's syndrome pathogenesis and is L-DOPA therapeutic tolerance formation was discussed.     

High-performance liquid chromatographic determination of dopamine sulfoconjugates in urine after l-DOPA administration

A procedure was developed for the separation and determination of dopamine-3-O-sulfate (DM-3-S) and dopamine-4-O-sulfate (DM-4-S) in the urine of subjects administered l-DOPA. The method consists of sample preparation using cation- and anion-exchange resins followed by determination of the sulfates by high-performance liquid chromatography. The addition recoveries were 96 ± 2.9% (S.D.) for DM-3-S and 93 ± 3.0% (S.D.) for DM-4-S. Twenty samples could be measured per day. When every 2-h urine specimen from normal subjects was analysed after l-DOPA administration (0.5 g), the maximum excretion of each sulfate was observed in the second 2-h specimen. For the first 6 h 7.5 ± 1.5% (S.D.) of the administered l-DOPA was excreted as DM-O-sulfates. During this time, the ratio of DM-4-S to the DM-O-sulfates was 11.7 ± 0.58% (S.D.).     

Event-related EEG changes preceding saccadic eye movements before and after dry immersion

Objectives of this work were to quantify antisaccade characteristics, presaccadic slow negative EEG-potentials, and event-related EEG frequency band power (theta, alpha1, alpha2, beta1, beta2 and beta3) changes (ERD) in healthy volunteers before and after 6-day simulated weightlessness (dry immersion).     

Non-dehalogenation mechanisms for excretion of radioiodine after administration of labeled antibodies

In patients or mice with cancer the pharmacokinetic behavior of radioiodinated and radiometal chelated antibodies has been observed to be different. Rapid clearance from the tissues and excretion into the urine can occur after injection of radioiodinated antibodies. These observations have been interpreted to reflect in vivo dehalogenation of the antibody. This publication describes a variety of other mechanisms that can underlie these phenomena. These mechanisms include receptor uptake and catabolism of antibody and instability of the labeled antibody due to the labeling conditions. Specifically, the relative masses of chloramine-T and antibody in the iodination reaction mixture, the level of iodination of the antibody, and the amount of antibody administered to the recipient are all factors which can influence the clearance of radioiodinated antibody from the recipient. The final determinant for the different behavior of radioiodinated and In-111 metal chelated antibody relate to the different biologic pathways of indium when compared to iodine.     

Noradrenergic transmission in isolated guinea-pig intestine following in vivo administration of antibodies to dopamine beta-hydroxylase.

The effectiveness of transmission from noradrenergic nerves supplying the guinea-pig ileum was evaluated in normal preparations and in preparations taken from animals injected 18 h to 4 days previously with antiserum to dopamine beta-hydroxylase. Degeneration of the nerves following the antiserum was monitored histochemically in the same preparations. A decline in the effectiveness of transmission, which paralleled the degeneration of the nerves, was observed. The earliest effects were detected at 18 h and the greatest effect was found at 2-4 days following the administration of antiserum. Binding of the antibodies has been detected as early as 6 h after injection. It is therefore concluded that binding of the antibodies to the nerves, per se, does not significantly compromise transmission, and that histochemical evidence of degeneration can be used to indicate the onset of functional deterioration of noradrenergic nerves following their exposure to antibodies to dopamine beta-hydroxylase.