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Critically attained threshold of cerebral hypoperfusion: the CATCH hypothesis of Alzheimer's pathogenesis.

This review discusses the experimental and clinical data which indicate that chronic cerebral hypoperfusion can affect metabolic, anatomic, and cognitive function adversely. In aged but not young animals, chronic brain hypoperfusion results in regional pre- and post-synaptic changes, protein synthesis abnormalities, energy metabolic dysregulation, reduced glucose utilization, cholinergic receptor loss, and visuo-spatial memory deficits. Additionally, aging animals that are kept for prolonged periods of time after chronic brain hypoperfusion, also develop brain capillary degeneration in CA1 hippocampus and neuronal damage extending from the hippocampal region to the temporo-parietal cortex where neurodegenerative tissue atrophy eventually forms. All these pathologic events occur in rodents in the absence of senile plaques and neurofibrillary tangles. Alzheimer brains reveal similar biochemical and structural changes as those experimentally induced in aging animals. Moreover, regional cerebral hypoperfusion is one of the earlier (if not the earliest) clinical manifestations in both the sporadic and familial forms of Alzheimer's disease. In addition, therapy that improves or increases cerebral perfusion is generally of some benefit to Alzheimer patients. Conversely, a variety of disorders with different etiologies that impair or diminish cerebral perfusion are reported to be risk factors for this dementia. These findings have prompted us to propose the concept that advanced aging in the presence of a vascular risk factor can converge to create a critically attained threshold of cerebral hypoperfusion (CATCH) that triggers regional brain microcirculatory disturbances and impairs optimal delivery of energy substrates needed for normal brain cell function. The outcome of this defect generates a chain of events leading to the progressive evolution of brain metabolic, cognitive and tissue pathology that characterize Alzheimer's disease. The possible role of CATCH in familial and early onset Alzheimer's disease is briefly discussed from a theoretical vantagepoint. The growing and most recent evidence in support of the CATCH concept is the focus of this review.

Alzheimer Disease↗
PubMed1985

Animal intelligence as encephalization.

There is no consensus on the nature of animal intelligence despite a century of research, though recent work on cognitive capacities of dolphins and great apes seems to be on one right track. The most precise quantitative analyses have been of relative brain size, or structural encephalization, undertaken to find biological correlates of mind in animals. Encephalization and its evolution are remarkably orderly, and if the idea of intelligence were unknown it would have to be invented to explain encephalization. The scientific question is: what behaviour or dimensions of behaviour evolved when encephalization evolved? The answer: the relatively unusual behaviours that require increased neural information processing capacity, beyond that attributable to differences among species in body size. In this perspective, the different behaviours that depend on augmented processing capacity in different species are evidence of different intelligences (in the plural) that have evolved.

Adaptation, Biological↗
PubMed1989

Phylogenesis and nutrition.

The evolution of man is connected with a life-style of hunting and gathering, and with the development and use of tools. The success of tools promoted the evolution of brain, thinking and skills. The food sources--animal and plant--remained the same during the whole of evolution. But the proportions of foods, preferences, preparations and the attainability changed. Evolution was a process continuously based on omnivorous nutrition. Compared to modern nutrition, paleolithic nutrition is richer in animal protein, vitamins, calcium, potassium and fibre, and poorer in fat and sodium. Saccharose, lactose and alcohol play no roles. The quality of the fat is marked by a high proportion of polyunsaturated fatty acids. This shift from a paleolithic diet to a modern diet caused nutritional risks, partly responsible for the dramatic increase in modern chronic diseases of heart, circulation and so on. Man's metabolism works in a stable genetic frame, derived during phylogenesis. We have to adapt our nutritional behaviour to its tolerances or we may succumb to disease and premature death. While our paleolithic metabolism is overdone with modern nutrition, our psychological heritages press in the direction of overdoing.

Agriculture↗
PubMed2000

Cortical organization in insectivora: the parallel evolution of the sensory periphery and the brain.

Insectivores are traditionally described as a primitive group that has not changed much in the course of mammalian evolution. In contrast, recent studies reveal a great diversity of sensorimotor specializations among insectivores adapted to a number of different ecological niches, indicating that there has been significant diversification and change in the course of their evolution. Here the organization of sensory cortex is compared in the African hedgehog (Atelerix albiventris), the masked shrew (Sorex cinereus), the eastern mole (Scalopus aquaticus), and the star-nosed mole (Condylura cristata). Each of these four closely related species lives in a unique ecological niche, exhibits a different repertoire of behaviors, and has a different configuration of peripheral sensory receptors. Corresponding specializations of cortical sensory areas reveal a number of ways in which the cortex has evolved in parallel with changes to the sensory periphery. These specializations include expansion of cortical representations (cortical magnification), the addition or loss of cortical areas in the processing network, and the subdivision of areas into modules (barrels and stripes).

Animals↗
PubMed1986

Insulin receptors in lizard brain and liver: structural and functional studies of alpha and beta subunits demonstrate evolutionary conservation.

Specific insulin receptors are present in the liver and brain of the lizard Anolis carolinesis. In this study, the specific binding of 125I-insulin to the receptors showed time, temperature and pH dependency. Specific binding to crude membranes prepared from brain was 1-2% of the total radioactivity added compared to 4-5% in the crude membranes prepared from liver. Solubilization and wheat germ agglutinin purification of the membranes resulted in an increase in the specific binding (per mg of protein) between 6 and 32 times for liver membranes and 13-186 for brain membranes. Binding inhibition of tracer insulin by unlabeled porcine insulin was characteristic for insulin receptors with 50% inhibition for liver crude membranes at 60 ng/ml of porcine insulin and 0.7 ng/ml for purified brain insulin receptors. Chicken insulin was 2- to 3-fold more potent and proinsulin about 100 times less potent than porcine insulin. The alpha-subunits of liver and brain had apparent molecular weights on sodium dodecyl sulfate polyacrylamide gel electrophoresis of 135 kDa and 120 kDa respectively. Apparent molecular weights of beta subunits were 92 kDa for both tissues. Insulin stimulated phosphorylation of the beta subunit of both brain and liver receptors. Both tissues demonstrated tyrosine-specific phosphorylation, which was stimulated by insulin, of exogenously added artificial substrates. In addition, purified brain insulin receptor preparations contained an endogenous protein with apparent molecular weight of 105 kDa, whose phosphorylation was stimulated by insulin (10(-7) mol/l). This phosphoprotein was not immunoprecipitated by anti-insulin receptor antibodies. These studies suggest that the structural differences between brain and liver receptors previously demonstrated in the rat are also present in the lizard, which is about 300,000,000 years older than the mammalian species. Thus, there is strong evolutionary conservation of the brain insulin receptor.

Animals↗
PubMed2003

The expression of planarian brain factor homologs, DjFoxG and DjFoxD.

Recent accumulating evidence revealed that planarian central nervous system (CNS) has numerous functional domains distinguished by a large number of neural markers, suggesting that primitive animals which developed CNS already had the framework of the brain development. It is of interest to investigate genes which have been acquired at an early stage of evolution for brain pattern formation. One such candidate is FoxG1 (BF-1), specifically expressed in the telencephalon and implicated in brain development. We identified a FoxG1 (BF-1) homolog gene in planarians (DjFoxG). We also identified a FoxD class gene, DjFoxD. DjFoxG is expressed in the body and brain, with strong expression in the mesenchyme surrounding the gut. During regeneration, an intense anterior signal is detected, but this is not restricted to the head. DjFoxD is expressed in the mid-apex of the head, between the two lobes of the brain. Strong expression was detected in the mid-anterior blastema. Thus, FoxG and FoxD homologs do exist in planarians, but are regulated differently than those in vertebrates.

Amino Acid Sequence↗
PubMed1993

The role of essential fatty acids in neural development: implications for perinatal nutrition.

The brain is 60% structural lipid, which universally uses arachidonic acid (AA; 20:4n6) and docosahexaenoic acid (DHA; 22:6n-3) for growth, function, and integrity. Both acids are consistent components of human milk. Experimental evidence in animals has demonstrated that the effect of essential fatty acid deficiency during early brain development is deleterious and permanent. The risk of neurodevelopmental disorder is highest in the very-low-birth-weight babies. Babies born of low birth weight or prematurely are most likely to have been born to mothers who were inadequately nourished, and the babies tend to be born with AA and DHA deficits. Because disorders of brain development can be permanent, proper provision should be made to protect the AA and DHA status of both term and preterm infants to ensure optimum conditions for the development of membrane-rich systems such as the brain, nervous, and vascular systems.

Animals↗
PubMed1988

The brain of the basking shark (Cetorhinus maximus).

The brain of a basking shark is described for the first time. Allometrical analysis of brain-body weight relationships indicates that Cetorhinus maximus shows by far the lowest degree of cerebralization of any shark investigated to date, possibly reflecting its plankton-feeding mode of life. Furthermore, some external morphological features of the brain appear to be species-specific. The proportions of brain parts indicate a primitive vertebrate brain organization. The size of the telencephalon, 34% of the total brain, equals that in some other sharks, whereas the cerebellum, 30% of the total brain in the basking shark, is significantly larger than in any other shark investigated. Furthermore, C. maximus shows some peculiarities concerning the nuclear expansion in the telencephalon. A rather large caudal interhemispheric region is especially striking. The relation of brain volume to brain cavity volume is approximately 1:16.

Animals↗
PubMed2006

Broca's arrow: evolution, prediction, and language in the brain.

Brodmann's areas 44 and 45 in the human brain, also known as Broca's area, have long been associated with language functions, especially in the left hemisphere. However, the precise role Broca's area plays in human language has not been established with certainty. Broca's area has homologs in the great apes and in area F5 in monkeys, which suggests that its original function was not linguistic at all. In fact, great ape and hominid brains show very similar left-over-right asymmetries in Broca's area homologs as well as in other areas, such as homologs to Wernicke's area, that are normally associated with language in modern humans. Moreover, the so-called mirror neurons are located in Broca's area in great apes and area F5 in monkeys, which seem to provide a representation of cause and effect in a primate's environment, particularly its social environment. Humans appear to have these mirror neurons in Broca's area as well. Similarly, genetic evidence related to the FOXP2 gene implicates Broca's area in linguistic function and dysfunction, but the gene itself is a highly conserved developmental gene in vertebrates and is shared with only two or three differences between humans and great apes, five between humans and mice, and eight between humans and songbirds. Taking neurons and portions of the brain as discrete computational segments in the sense of constituting specific Turing machines, this evidence points to a predictive motor and conceptual function for Broca's area in primates, especially for social concepts. In human language, this is consistent with evidence from typological and cognitive linguistics.

Biological Evolution↗
PubMed1978

Activity of catechol-o-methyltransferase in brain regions and adrenal gland during the oestrus cycle.

The activity of the enzyme catechol-O-methyltransferase (COMT) during four different phases of the oestrus cycle were determined. Brain and hypothalamus had highest level of COMT activity during oestrus phase, while at pro-oestrus it was at its lowest level. COMT activity in the adrenal gland was also modified during the four phases with the maximum level at met-oestrus and minimum at pro-oestrus phase. The results provide evidence to show that COMT in the brain, hypothalamus and the adrenals is markedly affected by changes in physiological status of the female rats and its evolution in brain is different from adrenal gland during the oestrus cycle. The variations in the activity of COMT may be the consequence of modified endocrine activity which takes place naturally during oestrus cycle.

Adrenal Glands↗