Plastic changes to dendritic spines in the cerebellar and prefrontal cortices underlie the decline in motor coordination and working memory during successful aging.

Old age is the last stage of life and by taking a multidimensional view of aging, Neuroscientists have been able to characterize pathological or successful aging. Psychomotor and cognitive performance are recognized as two major domains of successful aging, with a loss of motor coordination and working memory deficits two of the most characteristic features of elderly people. Dendritic spines in both the cerebellar and prefrontal cortices diminish in aging, yet the plastic changes in dendritic spines have not been related to behavioral performance neither the changes in the cerebellar or prefrontal cortices. As such, motor coordination and visuospatial working memory (vsWM) was evaluated here in aged, 22-month-old rats, calculating the density of spines and the proportion of the different types of spines. These animals performed erratically and slowly in a motor coordination-related paradigm, and the vsWM was resolved deficiently. Spine density was reduced in aged animals, and the proportional density of each of the spine types studied diminished in both the brain regions studied. The loss of dendritic spines and particularly, the changes in the proportional density of the different spine types could underlie, at least in part, the behavioral deficits observed during aging. To our knowledge, this is the first study of the plastic changes in different dendritic spine types that might underlie the behavioral alterations in motor and cognitive abilities associated with aging. Further neurochemical and molecular studies will help better understand the functional significance of the plastic changes to dendritic spines in both successful and pathological aging.

Spinogenesis in spinal cord motor neurons following pharmacological lesions to the rat motor cortex. / Espinogénesis en motoneuronas de la médula espinal tras la lesión farmacológica de la corteza motora de ratas.

INTRODUCTION: Motor function is impaired in multiple neurological diseases associated with corticospinal tract degeneration. Motor impairment has been linked to plastic changes at both the presynaptic and postsynaptic levels. However, there is no evidence of changes in information transmission from the cortex to spinal motor neurons. METHODS: We used kainic acid to induce stereotactic lesions to the primary motor cortex of female adult rats. Fifteen days later, we evaluated motor function with the BBB scale and the rotarod and determined the density of thin, stubby, and mushroom spines of motor neurons from a thoracolumbar segment of the spinal cord. Spinophilin, synaptophysin, and ß iii-tubulin expression was also measured. RESULTS: Pharmacological lesions resulted in poor motor performance. Spine density and the proportion of thin and stubby spines were greater. We also observed increased expression of the 3 proteins analysed. CONCLUSION: The clinical symptoms of neurological damage secondary to Wallerian degeneration of the corticospinal tract are associated with spontaneous, compensatory plastic changes at the synaptic level. Based on these findings, spontaneous plasticity is a factor to consider when designing more efficient strategies in the early phase of rehabilitation.

Antiherpes simplex virus type 2 activity of the antimicrobial peptide subtilosin.

AIMS: In this study, we evaluated the antiviral activity of subtilosin, a cyclical peptide isolated from Bacillus amyloliquefaciens, against herpes simplex virus type 2 (HSV-2) in cell cultures and we investigated subtilosin mode of action. METHODS AND RESULTS: We determined, using a virus yield inhibition assay, that noncytotoxic concentrations of subtilosin inhibit HSV-2 replication in Vero cell cultures. Subtilosin strongly inhibited extracellular and total virus production even when it was added at 8 h postinfection indicating that not only virus release but also viral particle formation is impeded by the antiviral peptide. Although viral glycoprotein gD level of expression is not affected by the bacteriocin, an altered pattern of gD intracellular localization was detected by immunofluorescence assay in subtilosin-treated culture. On the other hand, at high concentrations, subtilosin displays virucidal action. CONCLUSIONS: Subtilosin displays antiviral and virucidal actions against HSV-2. The target of subtilosin inhibitory effect would be late stages of the viral replicative cycle such as viral glycoprotein intracellular transport. SIGNIFICANCE AND IMPACT OF THE STUDY: Given its antimicrobial activity and its safety for human tissues, subtilosin could represent a valuable alternative to be considered in the development of new microbicide formulations.

Cholera-like enterotoxin produced by Campylobacter jejuni. Characterisation and clinical significance.

The presence and clinical significance of enterotoxins produced by Campylobacter jejuni were investigated. The supernatant of a prototype virulent strain grown in supplemented medium induced intraluminal fluid secretion in rat ileal loop but not in rabbit ileal loop or the infant mouse assay. It induced elongation and increased intracellular cyclic AMP levels in Chinese hamster ovary cells. Toxin activity was blocked by cholera antitoxin and was destroyed by heat and high or low pH; its molecular weight is in the range 10(4)-10(5) daltons. Toxin production was detected in 24 of 32 C jejuni strains from patients with diarrhoea and 1 of 6 from carriers. Antibody response to autologous C jejuni somatic antigen was investigated in 19 subjects for whom serial serum specimens were available. A fourfold rise was observed in all 10 patients with enterotoxigenic C jejuni diarrhoea, in 1 of 3 patients with non-enterotoxigenic C jejuni, and in none of the symptomless carriers of non-enterotoxigenic strains. These findings demonstrate that C jejuni produces an enterotoxin that may be important in pathogenesis of diarrhoea.