Microglia phenotype diversity

Microglia, the tissue macrophages of the brain, have under healthy conditions a resting phenotype that is characterized by a ramified morphology. With their fine processes microglia are continuously scanning their environment. Upon any homeostatic disturbance microglia rapidly change their phenotype and contribute to processes including inflammation, tissue remodeling, and neurogenesis. In this review, we will address functional phenotypes of microglia in diverse brain regions and phenotypes associated with neuroinflammation, neurogenesis, brain tumor homeostasis, and aging.     

Defining the schizophrenia phenotype

Schizophrenia is a complex disease with multifactorial etiology. The schizophrenia phenotype has been traditionally defined by chronic psychosis and functional deterioration. However, the boundary of the phenotype is likely to be more extensive than the one defined by chronic psychosis. This is highlighted by the findings of subtle, schizophrenialike deficits in the nonschizophrenic, first-degree relatives of schizophrenic patients. Subtle clinical signs and symptoms, cognitive impairment particularly in attention and memory, and neurophysiologic deficits such as in sensory gating and smooth-pursuit eye movements all define aspects of the schizophrenia phenotype.     

The core Dravet syndrome phenotype

Dravet syndrome was described in 1978 by Dravet (1978) under the name of severe myoclonic epilepsy in infancy (SMEI). The characteristics of the syndrome were confirmed and further delineated by other authors over the years. According to the semiologic features, two forms have been individualized: (1) the typical, core, SMEI; and (2) the borderline form, SMEIB, in which the myoclonic component is absent or subtle. Clinical manifestations at the onset, at the steady state, and during the course of the disease are analyzed in detail for the typical Dravet syndrome, and the differential diagnosis is discussed. Onset in the first year of life by febrile or afebrile clonic and tonic-clonic, generalized, and unilateral seizures, often prolonged, in an apparently normal infant is the first symptom, suggesting the diagnosis. Later on, multiple seizure types, mainly myoclonic, atypical absences, and focal seizures appear, as well as a slowing of developmental and cognitive skills, and the appearance of behavioral disorders. Mutation screening for the SCN1A gene confirms the diagnosis in 70-80% of patients. All seizure types are pharmacoresistent, but a trend toward less severe epilepsy and cognitive impairment is usually observed after the age of 5 years.     

Dimensions and the psychosis phenotype

In this paper, we discuss the conceptual background for including a dimensional component to the DSM V diagnoses for psychoses. We review the evidence for a continuous distribution of psychosis like symptoms in the general population and summarise the research validating the clinical usefulness of psychopathological dimensions. We conclude that diagnostic models using both categorical and dimensional representations of psychosis have better predictive validity than either model independently. Dimensions do not appear to be diagnosis specific so a flexible scoring of dimensions across all psychotic and major affective disorders may be potentially more informative than a system where categorical diagnoses are kept artificially dimension-specific.     

Human malignant astrocytes express macrophage phenotype

Six well-characterized specimens of cultured astrocytoma cells were investigated with a panel of macrophage markers. Our results show that the macrophage markers OKM-1(CD11b), OKM5(CD36), EBM11(CD68), HAM56, Factor 13, α-1-antichymotrypsin, α-1-antitrypsin, ferritin and lysozyme are clearly reactive to neoplastic astrocytes whereas astrocytes in normal brain specimens are not reactive. In order to obtain further confirmation concerning the reactivity of tumor cells in vivo, we simultaneously measured by flow cytometric analysis DNA content and HAM56 immunoreactivity in a freshly obtained tumor specimen. In this experiment we found a marked reactivity of aneuploid cells to HAM56. The macrophage phenotype of malignant astrocytes may reflect a similarity in functions of these cells and tumor-associated macrophages which promote tumor growth via the production of growth factors and angiogenic factors. Furthermore, our findings implicate that demonstration of macrophages within malignant astrocytomas by using macrophage-specific antibodies must be cautiously considered.     

Hemiconvulsion-hemiplegia-epilepsy evolving to contralateral hemi-Lennox-Gastaut-like phenotype

Background

Hemiconvulsion-hemiplegia-epilepsy (HHE) involves infantile-onset acute hemiconvulsive febrile status epilepticus with subsequent unilateral cerebral atrophy and hemiparesis. Chronic epilepsy later develops, typically involving refractory focal seizures; however, the underlying pathophysiology of this epilepsy is not well understood.

The expanding phenotype of mitochondrial myopathy

PURPOSE OF REVIEW: Our understanding of mitochondrial diseases (defined restrictively as defects in the mitochondrial respiratory chain) continues to progress apace. In this review we provide an update of information regarding disorders that predominantly or exclusively affect skeletal muscle. RECENT FINDINGS: Most recently described mitochondrial myopathies are due to defects in nuclear DNA, including coenzyme Q10 deficiency, and mutations in genes that control mitochondrial DNA (mtDNA) abundance and structure such as POLG and TK2. Barth syndrome, an X-linked recessive mitochondrial myopathy/cardiopathy, is associated with altered lipid composition of the inner mitochondrial membrane, but a putative secondary impairment of the respiratory chain remains to be documented. Concerning the 'other genome', the role played by mutations in protein encoding genes of mtDNA in causing isolated myopathies has been confirmed. It has also been confirmed that mutations in tRNA genes of mtDNA can cause predominantly myopathic syndromes and - contrary to conventional wisdom - these mutations can be homoplasmic. SUMMARY: Defects in the mitochondrial respiratory chain impair energy production and almost invariably involve skeletal muscle, causing exercise intolerance, myalgia, cramps, or fixed weakness, which often affects extraocular muscles and results in droopy eyelids (ptosis) and progressive external ophthalmoplegia.