The adolescent brain and age-related behavioral manifestations

Inflammation and Alzheimer's disease.

Astrocytes are specialized glial cells that outnumber neurons by over fivefold. They contiguously tile the entire central nervous system (CNS) and exert many essential complex functions in the healthy CNS. Astrocytes respond to all forms of CNS insults through a process referred to as reactive astrogliosis, which has become a pathological hallmark of CNS structural lesions. Substantial progress has been made recently in determining functions and mechanisms of reactive astrogliosis and in identifying roles of astrocytes in CNS disorders and pathologies. A vast molecular arsenal at the disposal of reactive astrocytes is being defined. Transgenic mouse models are dissecting specific aspects of reactive astrocytosis and glial scar formation in vivo. Astrocyte involvement in specific clinicopathological entities is being defined. It is now clear that reactive astrogliosis is not a simple all-or-none phenomenon but is a finely gradated continuum of changes that occur in context-dependent manners regulated by specific signaling events. These changes range from reversible alterations in gene expression and cell hypertrophy with preservation of cellular domains and tissue structure, to long-lasting scar formation with rearrangement of tissue structure. Increasing evidence points towards the potential of reactive astrogliosis to play either primary or contributing roles in CNS disorders via loss of normal astrocyte functions or gain of abnormal effects. This article reviews (1) astrocyte functions in healthy CNS, (2) mechanisms and functions of reactive astrogliosis and glial scar formation, and (3) ways in which reactive astrocytes may cause or contribute to specific CNS disorders and lesions.

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Astrocytes: biology and pathology

• Recent research on schizophrenia has demonstrated that in this disorder the brain is not, strictly speaking, normal. The findings suggest that nonspecific histopathology exists in the limbic system, diencephalon, and prefrontal cortex, that the pathology occurs early in development, and that the causative process is inactive long before the diagnosis is made. If these findings are valid and not epiphenomena, then the pathogenesis of schizophrenia does not appear to fit either traditional metabolic, posttraumatic, or neurodegenerative models of adult mental illness. The data are more consistent with a neurodevelopmental model in which a fixed "lesion" from early in life interacts with normal brain maturational events that occur much later. Based on neuro-ontological principles and insights from animal research about normal brain development, it is proposed that the appearance of diagnostic symptoms is linked to the normal maturation of brain areas affected by the early developmental pathology, particularly the dorsolateral prefrontal cortex. The course of the illness and the importance of stress may be related to normal maturational aspects of dopaminergic neural systems, particularly those innervating prefrontal cortex. Some implications for future research and treatment are considered.

Implications of normal brain development for the pathogenesis of schizophrenia

Introduction to synaptic circuits, Gordon M.Shepherd and Christof Koch membrane properties and neurotransmitter actions, David A.McCormick peripheral ganglia, Paul R.Adams and Christof Koch spinal cord - ventral horn, Robert E.Burke olfactory bulb, Gordon M.Shepherd, and Charles A.Greer retina, Peter Sterling cerebellum, Rodolfo R.Llinas and Kerry D.Walton thalamus, S.Murray Sherman and Christof Koch basal ganglia, Charles J.Wilson olfactory cortex, Lewis B.Haberly hippocampus, Thomas H.Brown and Anthony M.Zador neocortex, Rodney J.Douglas and Kevan A.C.Martin Gordon M.Shepherd. Appendix: Dendretic electrotonus and synaptic integration.

The synaptic organization of the brain

Regional Dendritic Variation in Primate Cortical Pyramidal Cells

The properties of neurons in the nucleus ventralis lateralis (VL) of thalamus were examined by anatomical and electrophysiological methods and the following results were obtained:

1.

There were two types of projection fibers from VL to the motor cortex. One type projected to a limited area of the cortex, the other arborized extensively and projected to a wide area of the cortex.




2.

The widely arborizing projection fibers, i.e., wide projection fibers, showed a special terminal bush which was different from that of the specific projection fibers of VPL and spread as widely as 1.0 mm2 within the III layer of the motor cortex.




3.

Neither narrow nor wide projection fibers carried specific information from the periphery but rather diffuse information arising from deep structures such as joints and periosts.




4.

Both types of projection fibers branched somewhere in the white substance and projected to different areas of the motor cortex.




5.

The chronaxie of these fibers was about the same as that of PT cells but considerably longer than spinal interneurons. The excitability of these fibers was lower than that of PT cells indicating that weak intracortical microstimulation (ICMS) does not excite these fibers.




6.

The possible functional role of wide projection fibers was discussed in relation to the cortical efferent zones.

Characteristics of projections from the nucleus ventralis lateralis to the motor cortex in the cats: an anatomical and physiological study.

Neuronal changes in the brain of a Rett syndrome patient were examined in a frontal lobe biopsy performed at age 3 years and in the postmortem brain at age 15 years. In the brain biopsy, frontal cortex contained numerous scattered pyramidal neurons with cytoplasmic vacuolation and increased cytoplasmic density, with no neuronophagia or inflammation detected; electron microscopy showed these neurons to have large, lucent-appearing mitochondria, very abundant ribosomal content, and some lipofuscin granules. Postmortem brain 12 years later showed scattered neurons in frontal cortex, substantia nigra, and cerebellar folia, with increased electron density of the cytoplasm, stacks of ribosomal endoplasmic reticulum, and large amounts of disorganized membranous material, including autophagic-type organelles. Mitochondria of these neurons contained electron-dense, finely granular matrix inclusions; in the substantia nigra, some spherical mitochondrial inclusions completely filled the matrix space. Golgi preparati...

Arnold B. Scheibel

Papers

Regional Dendritic Variation in Primate Cortical Pyramidal Cells

Characteristics of projections from the nucleus ventralis lateralis to the motor cortex in the cats: an anatomical and physiological study.

Neuropathology of Rett syndrome: case report with neuronal and mitochondrial abnormalities in the brain.

Degeneration of the human Betz cell due to amyotrophic lateral sclerosis

Chapter 4 – The Methods of Golgi