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.

/pdf/astrocytes-biology-and-pathology-2hq13zf0bo.pdf

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

Degeneration and regeneration of the nervous system

http://old.nbu.bg/cogs/events/2002/materials/Eran/Fiber%20composition%20of%20the%20human,%20corpus%20callosum.pdf

Fiber composition of the human corpus callosum.

A neurohistological correlate of schizophrenia

Progressive dendritic changes in aging human cortex.

This quantitative Golgi study extends our investigation of relationships between cortical dendrite systems in humans and higher cognitive functions. Here we examine the relationship between the basilar dendrites of supragranular pyramidal cells in Wernicke's area and selected intrinsic (i.e., gender and hemisphere) and extrinsic (i.e., education and personal history) variables. Tissue was obtained from 20 neurologically normal right-handers: 10 males (Mage = 52.2) and 10 females (Mage = 47.8). Several independent variables were investigated: GENDER (male, female), HEMISPHERE (left, right), and EDUCATION (less than high school, high school, and university). These were evaluated according to Total Dendritic Length, Mean Dendritic Length, and Dendritic Segment Count. A distinction was made between proximal (1st, 2nd, and 3rd order) and ontogenetically later developing distal (4th order and above) branches. There was significant interindividual variation in dendritic measurements, which roughly reflected individuals' personal backgrounds. Females exhibited slightly greater dendritic values and variability than males across the age range examined. On the whole, the left hemisphere maintained a slight advantage over the right hemisphere for all dendritic measures when all subjects were pooled, but these differences were not in a consistent direction across individuals. Education had a consistent and substantial effect such that dendritic measures increased as educational levels increased. Dendritic differences between independent variable levels were most clearly illustrated in the total dendritic length of 3rd and 4th order branches. Distal dendritic branches appeared to exhibit greater epigenetic flexibility than proximal dendrites. The present findings concur with environmental enrichment research results in animals and suggest that dendritic systems in humans function as a sensitive indicator of an individual's (a)vocational activities.

Arnold B. Scheibel

Papers

Degeneration and regeneration of the nervous system

Fiber composition of the human corpus callosum.

A neurohistological correlate of schizophrenia

Progressive dendritic changes in aging human cortex.

A quantitative dendritic analysis of Wernicke's area in humans. II. Gender, hemispheric, and environmental factors.