Vasiliki Costa

Systemic immune aberrations in Alzheimer's disease patients

The role of chronic inflammation in the pathogenesis of Alzheimers disease (AD) has been implied in a plethora of studies. The objective of the present study was to evaluate the immune alterations and the immunological markers in patients suffering from AD. IL-1alpha, IL-2, IL-6, IL-8, IL-10, TNF-alpha cytokine and helper/inducer (CD4), suppressor/cytotoxic (CD8) T lymphocyte levels were investigated in patients with various degrees of cognitive impairment (mild-moderate and severe stage), as well as in age-matched non demented controls. Cytokines were measured using the ELISA immunoassay method and lymphocytes using flow cytometry. Results showed a significant TNF-alpha increase in patients of severe stage serum compared to controls as well as a significant decrease of CD4 lymphocyte subpopulation levels in patients of severe stage compared to those of mild-moderate stage patients and controls. No significant differences were observed on IL-1alpha, IL-2, IL-6, IL-8, IL-10 cytokine levels and on CD8, CD4/CD8 lymphocyte subpopulations levels between patients and controls neither between mild moderate and severe stage patients. CD4 lymphocyte subpopulation and cytokine IL-2 were revealed as having a significant relationship (positive and negative respectively) with the MMSE score of patients. Data suggest the existence of detectable changes of peripheral immune system in AD.

CYTOKINES IN ALZHEIMER'S DISEASE AND VASCULAR DEMENTIA

The levels of interleukin 1β, interleukin 6, and interleukin 10 were elevated in the serum of patients with dementia. No statistically significant correlation was recorded in the interleukin levels among patients with Alzheimers disease and vascular dementia. Also, no significant correlation was observed in the interleukin levels in the serum and the severity of dementia. However, a significant correlation was found between IL-6 and tumor necrosis factor-α (TNF-α) levels and age. The levels of IL-1β and IL-6 were positively correlated with hypertension, and IL-2 levels were negatively correlated. No correlation was found between depressive symptoms and levels of cytokines in the serum.

Morphological Changes of the Human Purkinje Cells and Deposition of Neuritic Plaques and Neurofibrillary Tangles on the Cerebellar Cortex of Alzheimer’s Disease

Alzheimer’s disease is a neurodegenerative disorder, characterized by progressive decline in memory and in social performance. The morphological hallmarks of the disease are neuronal loss, loss of dendritic spines, neurofibrillary degeneration and neuritic plaques mainly in the hippocampus and the cortex of the cerebral hemispheres. This study is based on the morphological analysis of the cerebellar cortices of eight brains, 4 patients suffered from Alzheimer’s disease and 4 normal controls, by Golgi method, as well as Nissl, Gallyas’, Bielschowsky’s, Methenamine Silver staining and Congo red methods. Although typical neuritic plaques were not seen in the cerebellar cortex and the diffuse plaques found in the cerebellum in far smaller proportion than plaques in the prefrontal and parietal cortices of the same cases, Golgi impregnation technique revealed a loss of Purkinje cells and a marked decrease in the density of dendritic arborization.

Dendritic Pathology and Spinal Loss in the Visual Cortex in Alzheimer's Disease: A Golgi Study in Pathology

ABSTRACT Alzheimers disease is a neurodegenerative disorder characterized by progressive decline in memory, loss of professional skills, impairment of judgement and behavior, and decline in social performances. In terms of neuropathology, the morphological hallmarks of the disease are the accumulation of alpha–beta peptide and the neurofibrillary degeneration, associated with synaptic alterations, involving mostly the dendritic spines. This study is based on the morphological analysis of 10 brains, 5 of which were obtained from patients who suffered from Alzheimers disease and 5 from nondemented senile individuals used as control group. The segments taken in major from the occipital lobe were studied with the use of Golgi method, as well as Gallyas’ and Bielschowski’ s staining methods. In most of the pyramidal cells in the affected brains, there seems to be important spine loss and extensive dendrite pathology. Apical dendrites are distorted and tortuous. Horizontal dendritic arborization is severely decreased leading to an amputated, bell-shaped cell soma. Senile plaques have been often revealed, and neurofibrillary changes have also been noticed.

INTRAVENTRICULAR ADMINISTRATION OF SUBSTANCE P INDUCES UNATTACHED PURKINJE CELL DENDRITIC SPINES IN RATS

Substance P was infused in the lateral ventricles of twenty Lewis rats for twenty days. The animals under the influence of the substance P demonstrated grooming of the head, the body and the forepaws. On the twentieth day the animals were sacrificed and the cerebellar cortex was processed for electron microscopy. The ultrastructural analysis revealed that although the granule cells, the parallel fibers and the systems of the afferent fibers were intact, numerous unattached Purkinje cell dendritic spines were seen embedded in the soma of the astrocytes, demonstrating postsynaptic differentiation. Numerous unattached spines of the secondary and tertiary dendritic branches of the Purkinje cells were also seen in the molecular layer surrounded by astrocytic sheath. Free unattached spines were also seen not surrounded by any astrocytic process, which did not demonstrate any postsynaptic specialization. The development of unattached Purkinje cell dendritic spines, in an otherwise intact cerebellar cortex, following the intraventricular administration of substance P, suggests that it may act as local growth factor, enforcing the preprogrammed-capability of the Purkinje cells in developing new synaptic surfaces.

CLINICAL CASE: VERMIS HYPOPLASIA WITH FEATURES OF SMITH-LEMLI-OPITZ SYNDROME

This article attempts to describe a very unusual case of a boy aged 15, who has had intractable epileptic phenomena, mental retardation, megalocephaly, micrognathy, syndactyly, small tongue, hypoplastic genitalia, gynecomasty, obesity, and slight left body hemiatrophy. Neurologically the patient has had hypotonia of the lower limbs, cerebellar dysfunction including horizontal nystagmus, bilateral intention tremor, dysdiadokokinesia, gait ataxia. The clinical investigation revealed low plasma cholesterol and hypoplasia of the vermis in MRI. The epileptic phenomena were intractable and polymorphous. One should have thought that this is an unusual case of Smith-Lemli-Opitz syndrome associated with features of Joubert syndrome.

Intraventricular Administration of Substance P Increases the Dendritic Arborisation and the Synaptic Surfaces of Purkinje Cells in Rat's Cerebellum

Substance P was infused in the lateral ventricles of twenty Lewis rats for twenty days. On the twentieth day the animals were sacrificed and the cerebellar cortex was processed for electron microscopy. The ultrastructural morphometric analysis revealed that the Purkinje cell dendritic arborisation and the number of the synapses between the parallel fibres and the Purkinje cell dendritic spines were much higher than in control animals. Numerous unattached spines of the secondary and tertiary dendritic branches of the Purkinje cells were also seen in the molecular layer either free or surrounded by astro-cytic sheath. The increased number of synapses between the Purkinje cell dendrites and the parallel fibres in the animals, which received substance P intraventricularly, in correlation to control animals, supports a neurotrophine-like activity of the substance P in the mammalian cerebellum, enforcing the pre-programmed capability of the Purkinje cells to develop new synaptic surfaces.

The Nucleus Basalis of Meynert of the Human Brain: A Golgi and Electron Microscope Study

The nucleus basalis of Meynert of normal brains, aged from 15 to 73 years was studied in Golgi preparations and in electron microscopy. The nucleus is composed of large triangular, polyhedral and bipolar cells which are intermixed with numerous small or medium-sized spiny neurons. All of the neurons form a dense three dimensional dendritic arborization, with numerous secondary and tertiary dendritic branches studded with spines. The ultrastructural analysis revealed numerous axodendritic and axosomatic synapses between the spines. The ultrastructural analysis revealed numerous axodendritic and axosomatic synapses between the spiny neurons and the large triangular and polyhedral neurons. The presynaptic axonic profiles are plenty of ellipsoid and round synaptic vesicles. Large presynaptic terminals are seen frequently surrounded by numerous dendritic spines forming synaptic glomeruli, in all the areas of the nucleus basalis of Meynert. An age depended decrease of the number of neurons was noticed affecting mainly the population of the spiny neurons. Although in senile and presenile dementias an impressive loss of the cholinergic neurons of the nucleus basalis was reported, in normal aging the large cholinergic neurons of the nucleus basalis seems to be intact, whereas the medium and small shaped spiny neurons are decreased in number suggesting that the GABA-ergic neurons are principally affected.

Dendritic, Axonal, and Spinal Pathology of the Purkinje Cells and the Neurons of the Dentate Nucleus After Long-Term Phenytoin Administration A Case Report

Phenytoin is a commonly prescribed anticonvulsant drug; however, there is evidence that long-term administration is related to cerebellar ataxia, cerebellar atrophy, loss of Purkinje cells, and hyperplasia of Bergman glia cells. The aim of the present study was to detect and describe any possible alterations of the Purkinje cells, and neurons of the dentate nucleus, as those can be seen with the use of silver impregnation techniques, such as Golgi and Nauta method. The study was performed on a 7-year-old boy who was under phenytoin treatment for more than 3.5 years and had clinical manifestations of cerebellar ataxia. Golgi silver impregnation technique revealed substantial loss of dendritic spines and tertiary dendritic branches, both on the Purkinje cells and the neurons of the dentate nucleus, whereas the Nauta method demonstrated swollen and degenerated axons of Purkinje cells.

A case of intractable epilepsy in a double cortex syndrome.

This article describes a very rare case of a double cortex syndrome in a man aged 32 years old who started from the age of 14 years having seizures and many other epileptic manifestations that continue to the present age, being always intractable to various therapeutic regimes. The neuroimaging revealed cortical ectopias in the cingulum, the visual cortex, in the middle part of the superior temporal gyrus, in the frontal pole as well as in the middle area of precentral gyrus. This article attempts to underline the behavioral disturbances, the learning difficulties, the psychological fluctuations, and the multitude of the seizures that have been released during the clinical course of the patient. The article attempts to correlate the clinical phenomena of the patient and the resistance to therapeutical interventions with the morphological changes as they have been visualized by the neuroimaging techniques, reviewing in addition relevant cases from the literature.