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Neuropeptide role of both peptide YY and neuropeptide Y in vertebrates suggested by abundant expression of their mRNAs in a cyclostome brain.

The evolution of the neuropeptide Y (NPY) family of peptides has been unclear despite sequence information from many vertebrates. We describe here two NPY-related peptides deduced from cDNA clones of the river lamprey (Lampetra fluviatilis), a cyclostome providing one of the best models of a primitive vertebrate brain. One peptide corresponds to NPY as it has 83% identity to human NPY and its mRNA is expressed in the lateral brainstem, dorsal spinal cord and retina. The second lamprey peptide corresponds anatomically to peptide YY (PYY) as its mRNA is found in gut cells and in medial brainstem neurons. Its sequence is 60-70% identical to both PYY and NPY of mammals. These data suggest that the gene duplication leading to NPY and PYY had already occurred in the ancestral vertebrate 450 million years ago. The expression of the presumed PYY homolog in both gut and central nervous system indicates that PYY has served the dual role as a hormone and a neuropeptide from an early stage in vertebrate evolution. The similarities in the location of NPY- and PYY-expressing cells between lamprey and mammals suggest that the functions of these peptides may have been conserved.

Amino Acid Sequence↗

Independent evolution of HIV type 1 in different brain regions.

HIV-1-associated brain pathology exhibits regional variability and we therefore studied the genetic differences in the V1-V5 domains of the HIV env gene in up to four regions of brain (frontal lobe, basal ganglia, medial temporal lobe, and nonmedial temporal lobe) from three patients. We found that in each separate brain region HIV-1 forms different quasispecies and that there is little gene flow among these regions. In further support of brain region-specific evolution of HIV-1, we analyzed amino acid signatures in these clones. In addition to known amino acid signatures associated with macrophage tropism and the lack of syncytium formation, we found 15 majority amino acid signature patterns from the V1-V5 env sequences associated with the neuroanatomical regions analyzed from the three individuals. Furthermore, on average, intrabrain genetic distances for the HIV-1 env were estimated to be much smaller than genetic distances between brain regions. Specific strains of HIV-1 may be neurotropic or neuroinvasive (replication preference in brain tissue) and may contribute to pathology, cognitive loss, and neuropsychiatric disease.

Adult↗

Can fat explain the human brain's big bang evolution?-Horrobin's leads for comparative and functional genomics.

When David Horrobin suggested that phospholipid and fatty acid metabolism played a major role in human evolution, his 'fat utilization hypothesis' unified intriguing work from paleoanthropology, evolutionary biology, genetic and nervous system research in a novel and coherent lipid-related context. Interestingly, unlike most other evolutionary concepts, the hypothesis allows specific predictions which can be empirically tested in the near future. This paper summarizes some of Horrobin's intriguing propositions and suggests as to how approaches of comparative genomics published in Cell, Nature, Science and elsewhere since 1997 may be used to examine his evolutionary hypothesis. Indeed, systematic investigations of the genomic clock in the species' mitochondrial DNA, the Y and autosomal chromosomes as evidence of evolutionary relationships and distinctions can help to scrutinize associated predictions for their validity, namely that key mutations which differentiate us from Neanderthals and from great apes are in the genes coding for proteins which regulate fat metabolism, and particularly the phospholipid metabolism of the synapses of the brain. It is concluded that beyond clues to humans' relationships with living primates and to the Neanderthals' cognitive performance and their disappearance, the suggested molecular clock analyses may provide crucial insights into the biochemical evolution-and means of possible manipulation-of our brain.

Animals↗

Otx genes in the development and evolution of the vertebrate brain.

Most of the gene candidates for the control of developmental programmes that underlie brain morphogenesis in vertebrates are the orthologues of Drosophila genes coding for signalling molecules or transcription factors. Among these, the orthodenticle group, including the Drosophila orthodenticle (otd) and the vertebrate Otx1 and Otx2 genes, is mostly involved in fundamental processes of anterior neural patterning. In mouse, Drosophila and intermediate species otd/Otx genes have shown a remarkable similarity in expression pattern suggesting that they could be part of a conserved control system operating in the brain and different from that coded by the HOX complexes controlling the hindbrain and spinal cord. In order to verify this hypothesis, a series of mouse models have been generated in which the functions of the murine Otx genes were: (i) fully inactivated, (ii) replaced with each other, and (iii) replaced with the Drosophila otd gene. The data obtained highlight a crucial role for the Otx genes in specification, regionalization and terminal differentiation of rostral central nervous system and lead to hypothesize that modification of their regulatory control may have influenced the morphogenesis and evolution of the brain.

Alleles↗

Complementary use of T2-weighted and postcontrast T1- and T2*-weighted imaging to distinguish sites of reversible and irreversible brain damage in focal ischemic lesions in the rat brain.

The evolution of a photochemically induced cortical infarct was monitored using T2-, postcontrast (GdDOTA) T1-, and postcontrast (DyDTPA-BMA) T2*-weighted NMR imaging techniques. Data acquired with these different NMR imaging types were compared, both qualitatively and quantitatively. The T2*-weighted NMR images after spordiamide injection (DyDTPA-BMA) were perfusion-weighted images that allowed the differentiation between several infarct-related areas in terms of different degrees of perfusion deficiency. No quantitative information on cerebral blood flow (CBF) was obtained. A clear distinction was made between areas with a complete lack of CBF located in the core of the lesion and temporary CBF insufficiencies in the rim surrounding this core. Concomitant observations on T2-weighted and postcontrast T1-weighted images revealed the same temporary rim characterized by an increased water content, and an intact blood-brain barrier (BBB), as well as by reduced perfusion. This rim appeared within the first hours after infarct induction, reached a maximum 24 h later, and lasted between 3-5 days, when its size gradually decreased until complete disappearance. These observations suggest the existence of an area at risk. Only on postcontrast T1-weighted images, the core of the lesion remained visible during the whole experimental period (10 days) and reflected in all likelihood the irreversibly damaged ischemic central core. The combined application of different NMR imaging techniques when studying focal cerebral infarctions in the rat brain allowed us to distinguish, in terms of NMR characteristics, zones of reversible from irreversible brain damage and to estimate the severity of the damage. This might offer an appropriate experimental setup for the screening of cerebroprotective compounds.

Animals↗

Parallel evolution in mammalian and avian brains: comparative cytoarchitectonic and cytochemical analysis.

Comparative morphology, which is based on the selection theory of evolution, analyses the impact of function upon structure and, therefore, emphasizes the adaptive events and biological advantage during the evolution of organs. A comparison based on analogies is described here as an adequate method. The hypothesis is proposed that the evolution of the brain follows the same trends in birds as in mammals. This hypothesis is proved by (1) allometric studies of brain weight and brain structure volume in relation to body weight in mammals and birds; (2) architectonic studies using image analysis on cell and fibre stains as well as on histochemical preparations and receptor autoradiography; and (3) hodological studies with injections of [3H]leucin, HRP and WGA-HRP. The results reveal a vast amount of structural and functional similarities in avian and mammalian brain organization, especially an expansion of structures that permit multimodal integration capacity in the telencephalon. Thus, a parallel evolution occurred in these two groups of vertebrates. It is argued that this may be a general phenomenon in evolution. A cladistic approach, which is based on the concept of homologies (plesio-, apomorphies), pushes aside the existence of analogies. For this reason, cladism does not seem to be a method to answer questions of evolutionary morphology adequately.

Animals↗

Water diffusion compartmentation at high b values in ischemic human brain.

BACKGROUND AND PURPOSE: We studied the evolution of brain water compartments during the early stage of ischemic stroke. METHODS: Diffusion-weighted imaging was performed at 1.5 T in 10 volunteers and 14 patients with stroke. We used a single-shot echo-planar technique with 11 b values of 0-5000 s/mm(2). Regions of interest were selected in the white matter (WM) and striatum of the volunteers and in the ischemic core of the patients. Measurements were fitted on the basis of a biexponential decay with the b factor as follows: S(b) = S(0)[(f(slow) x exp(-b x ADC(slow)) + (f(fast) x exp(-b x ADC(fast))] where S(b) is the signal intensity in the presence of a diffusion gradient, S(0) is the signal intensity without diffusion sensitization, ADC(slow) and ADC(fast) are the respective apparent diffusion coefficients (ADCs) of slow diffusing compartments (SDCs) and fast diffusing compartments (FDCs), and f(slow) and f(fast) the respective contributions to the signal intensity of SDC and FDC. RESULTS: In healthy subjects, FDC represents 74.3 +/- 3.1% of brain water, with ADC(fast) = (124.6 +/- 12.0) x 10(-5) mm(2)/s and ADC(slow) = (15.5 +/- 3.9) x 10(-5) mm(2)/s. In stroke, decreased FDC (49.1% +/- 10.9%; P = 1.05 x10(-5)) and increased ADC(slow) ([22.4 +/- 8.1] x 10(-5) mm(2)/s; P = 8.07 x 10(-3)) were observed, but ADC(fast) was not significantly changed ([135.6 +/- 25.7] x 10 (-5) mm(2)/s; P =.151). CONCLUSION: The restricted diffusion observed in the early stroke is mainly related to a redistribution of water from the FDC to the SDC.

Body Water↗

Taxonomic differences in the scaling of brain on body weight among mammals.

Theories for the evolution of brain weight in mammals suggest that closely related species have diverged largely as a result of selection for differences in body weight, but that differences among more distantly related species have arisen due to greater net directional selection on brain weight. This pattern of changing selection causes brain weight to evolve more slowly than body weight among closely related species, such as those in the same genus, than among more distantly related species, such as those from different families or orders; a phenomenon known as the "taxon-level effect." Thus, brain weight differs more for a given difference in body weight as the species compared are more distantly related. An alternative explanation for the taxon-level effect is proposed. Distantly related species are more likely to inhabit different ecological conditions than are more closely related species. Where the taxon-level effect occurs, brain weight appears to have evolved in response to the demands of these different ecological conditions. As a consequence, brain weight differs more among distantly related species, for any given difference in body weight, than among closely related species. This effect, rather than a progressive pattern of changing selection pressures, may account for the taxon-level effect in mammals.

Animals↗