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PubMed2006

The jewels of our genome: the search for the genomic changes underlying the evolutionarily unique capacities of the human brain.

The recent publication of the initial sequence and analysis of the chimp genome allows us, for the first time, to compare our genome with that of our closest living evolutionary relative. With more primate genome sequences being pursued, and with other genome-wide, cross-species comparative techniques emerging, we are entering an era in which we will be able to carry out genomic comparisons of unprecedented scope and detail. These studies should yield a bounty of new insights about the genes and genomic features that are unique to our species as well as those that are unique to other primate lineages, and may begin to causally link some of these to lineage-specific phenotypic characteristics. The most intriguing potential of these new approaches will be in the area of evolutionary neurogenomics and in the possibility that the key human lineage-specific (HLS) genomic changes that underlie the evolution of the human brain will be identified. Such new knowledge should provide fresh insights into neuronal development and higher cognitive function and dysfunction, and may possibly uncover biological mechanisms for information storage, analysis, and retrieval never previously seen.

Animals↗
PubMed2000

Chordate evolution and the origin of craniates: an old brain in a new head.

The earliest craniates achieved a unique condition among bilaterally symmetrical animals: they possessed enlarged, elaborated brains with paired sense organs and unique derivatives of neural crest and placodal tissues, including peripheral sensory ganglia, visceral arches, and head skeleton. The craniate sister taxon, cephalochordates, has rostral portions of the neuraxis that are homologous to some of the major divisions of craniate brains. Moreover, recent data indicate that many genes involved in patterning the nervous system are common to all bilaterally symmetrical animals and have been inherited from a common ancestor. Craniates, thus, have an "old" brain in a new head, due to re-expression of these anciently acquired genes. The transition to the craniate brain from a cephalochordate-like ancestral form may have involved a mediolateral shift in expression of the genes that specify nervous system development from various parts of the ectoderm. It is suggested here that the transition was sequential. The first step involved the presence of paired, lateral eyes, elaboration of the alar plate, and enhancement of the descending visual pathway to brainstem motor centers. Subsequently, this central visual pathway served as a template for the additional sensory systems that were elaborated and/or augmented with the "bloom" of migratory neural crest and placodes. This model accounts for the marked uniformity of pattern across central sensory pathways and for the lack of any neural crest-placode cranial nerve for either the diencephalon or mesencephalon. Anat Rec (New Anat) 261:111-125, 2000.

Anatomy, Comparative↗
PubMed2001

The LIM-homeodomain gene family in the developing Xenopus brain: conservation and divergences with the mouse related to the evolution of the forebrain.

A comparative analysis of LIM-homeodomain (LIM-hd) expression patterns in the developing stage 32 Xenopus brain is presented. x-Lhx2, x-Lhx7, and x-Lhx9 were isolated and their expression, together with that of x-Lhx1 and x-Lhx5, was analyzed in terms of prosomeric brain development and LIM-hd combinatorial code and compared with mouse expression data. The results show an almost complete conservation of expression patterns in the diencephalon. The Lhx1/5 and Lhx2/9 subgroups label the pretectum/ventral thalamus/zona limitans versus the dorsal thalamus, respectively, in alternating stripes of expression in both species. Conversely, strong divergences in expression patterns are observed between the telencephalon of the two species for Lhx1/5 and Lhx2/9. Lhx7 exhibits particularly conservative patterns and is proposed as a medial ganglionic eminence marker. The conservation of diencephalic segments is proposed to mirror the conservative nature of diencephalic structures across vertebrates. In contrast, the telencephalic divergences are proposed to reflect the emergence of significant novelty in the telencephalon (connectivity changes) at the anamniote/amniote transition. Moreover, the data allow the new delineation of pallial and subpallial domains in the developing frog telencephalon, which are compared with mouse subdivisions. In the pallium, the mouse combinatorial expression of LIM-hd is notably richer than in the frog, again possibly reflecting evolutionary changes in cortical connectivity.

Animals↗
PubMed1989

[Evolution of venous cerebral infarction and brain edema--an experimental study of sagittal sinus obstruction].

Superior sagittal sinus with/without neighboring venous system of 36 mongrel cats were occluded by cyanoacrylate polymer after i.v. administration of Evans-blue (EB). Thereafter, the cats were sacrificed 1, 3, 6, 12, 24, 72 or 120 hours after sinus-vein occlusion. According to the degree of occluded region, the cats were divided into two groups; group A (GA) and B (GB). GA showed only superior sagittal sinus occlusion, while many cortical veins were also occluded in GB. No EB nor histological changes were found in 13 cats of GA and 4 sham operated cats, while EB distribution was observed in all 20 cats of GB. The other 3 cats of GA showed a little EB in gyrus lateralis. EB distribution of GB were divided into two types. Type 1 showed EB mainly in the cortical gray matter, while type 2 showed massive EB extravasation in the white matter as well. Edematous changes with gliosis in its resolution phase, were observed in type 1. In addition, EB free zone was formed along with U-fiber zone (cortico-medullary junction) in the cats of later phase (72 hours after occlusion). The findings of EB extension in the type 1 means the existence of blockage against edema evolution from cortex toward subcortical white matter. The cats of type 2 showed fulminant hemorrhagic changes which appeared depend on time interval. Although occurrence of pathological changes were rather earlier than that of cases of clinical cerebral sinus thrombosis, this pathological findings demonstrated the typical character of venous hemorrhagic infarction. In this paper, the similarity and difference between this model and clinical case of sinus-vein thrombosis were discussed. And the possible function of the U-fiber zone in the corticomedullary junction against edema evolution was suggested.

Animals↗
PubMed1998

[Arachnoid metastasis of renal cell carcinoma: review of forms of tumor dissemination and review of its metastasis in the nervous system].

Contribution of one case of renal cells carcinoma, in an adult man, that during evolution developed arachnoid metastasis. The patient was first seen for a brain haemorrhage due to a bleeding metastasis. In later studies, a renal cells carcinoma was found to be the primary site of the brain condition. The evolution showed neurological manifestations in the limbs, and the arachnoid metastasis was detected. The paper includes imaging studies of the referred disease both al brain, renal and spinal level with CT and NMR studies. A revision is made of the different dissemination forms of renal cells tumours, as well as a review of the existing literature with regard to the nervous system metastasis. No case has been found in this review relative to spinal arachnoid dissemination.

Arachnoid↗
PubMed1992

Structure and evolution of four POU domain genes expressed in mouse brain.

Four mouse POU domain genomic DNA clones--Brain-1, Brain-2, Brain-4, and Scip--and Brain-2 cDNA, which are expressed in adult brain, were cloned and the coding and noncoding regions of the genes were sequenced. The amino acid sequences of the four POU domains are highly conserved; sequences in other regions of the proteins also are conserved but to a lesser extent. The absence of introns from the coding regions of the four POU domain genes and the similarity of amino acid sequences of the corresponding proteins suggest that the coding region of the ancestral class III POU domain gene lacked introns and therefore may have originated by reverse transcription of a molecule of POU domain mRNA followed by insertion of the cDNA into germ cell genomic DNA. Additional duplications of the ancestral class III POU domain gene (or mRNA) would create the Brain-1, Brain-2, Brain-4, and Scip genes.

Amino Acid Sequence↗
PubMed1993

Further comments on the evolutionary origin of the mammalian brain.

This paper is an extension of a previous report on the origin of the mammalian neocortex. Two main aspects are elaborated. The first is the evolution of visual projections from the midbrain to the telencephalon, featuring the encephalization of visual functions. Associated to this, the progressive fusion of the two main visual systems (thalamofugal and tectofugal) in the mammalian telencephalon (striate and extrastriate cortex, respectively) is viewed in the context of increasing cortico-cortical connectivity in the evolution of the mammalian brain. In addition, the issue of a presumed homology between mammalian extrastriate cortex and reptilian anterior dorsal ventricular ridge (ADVR) is reviewed in some detail, and it is concluded that extrastriate cortex is a derived character of mammals while ADVR is a derived character of reptiles and birds. It is not likely that ADVR is ancestral to extrastriate cortex. The second aspect under analysis is the origin of the inverted (inside-out) lamination pattern of mammalian neocortex that differs from the outside-in pattern of reptilian cortex. Furthermore, mammals have developed a transient embryonic cell layer (the subplate zone) that serves as a waiting compartment for thalamic and cortico-cortical axons while their prospective target cells end their migration process to reach their final positions. It is postulated that both, inverted lamination and the subplate zone arose in evolution as successive and complementary strategies to maximize synaptic contacts between thalamic afferents and the new cortical cell types (belonging to prospective granular and supragranular layers) that were being originated at that moment.

Animals↗
PubMed1999

Mosaic structure of the human immunodeficiency virus type 1 genome infecting lymphoid cells and the brain: evidence for frequent in vivo recombination events in the evolution of regional populations.

In addition to immunodeficiency, human immunodeficiency virus type 1 (HIV-1) can cause cognitive impairment and dementia through direct infection of the brain. To investigate the adaptive process and timing of HIV-1 entry into the central nervous system, we carried out an extensive genetic characterization of variants amplified from different regions of the brain and determined their relatedness to those in lymphoid tissue. HIV-1 genomes infecting different regions of the brain of one study subject with HIV encephalitis (HIVE) had a mosaic structure, being assembled from different combinations of evolutionarily distinct lineages in p17(gag), pol, individual hypervariable regions of gp120 (V1/V2, V3, V4, and V5), and gp41/nef. Similar discordant phylogenetic relationships were observed between p17(gag) and V3 sequences of brain and lymphoid tissue from three other individuals with HIVE. The observation that different parts of the genome of HIV infecting a particular tissue can have different evolutionary histories necessarily limits the conclusions that can be drawn from previous studies of the compartmentalization of distinct HIV populations in different tissues, as these have been generally restricted to sequence comparisons of single subgenomic regions. The complexity of viral populations in the brain produced by recombination could provide a powerful adaptive mechanism for the spread of virus with new phenotypes, such as antiviral resistance or escape from cytotoxic T-cell recognition into existing tissue-adapted virus populations.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Quantitative assessment of glioblastoma invasion in vivo.

The aim of this study was the quantitative assessment of the time course and spatial distribution in brain of invading glioblastoma (GBM) cells using a recently described model consisting of RT2 rat GBM cells stably transfected with enhanced green fluorescent protein (eGFP) - called RT2-eGFP - and implanted in Fischer rats. Invasion throughout the brain was verified by confocal microscopy and immunocytochemical staining for eGFP. Rats were sacrificed on post-implantation days 3, 8, and time of death (TOD). First, the entire rat brain was disaggregated at each time point and viable RT2-eGFP cells were counted using flow cytometry with fluorescence as the marker. Next, 2 mm(3) samples of cortex from each of four brain quadrants (bifrontal and bioccipital) were disaggregated at each time point, with tumor cell quantification as before. Tumor cell density, averaged over the entire brain, reached a peak mid-way through its time course, leveling out by TOD. Tumor cell density within bulk tumor (BT) was greatest early in the evolution of the brain tumor, decreasing to its final value mid-way through its time course, due to necrosis. The greatest concentration of tumor cells was within BT, with up to an order of magnitude fewer cells in the periphery, while the number of brain tumor cells invading brain distant from BT remained constant from day 3 until TOD. BT size steadily increased after implantation, with an increasing portion due to central necrosis as time progressed, suggesting that this effect is an important contributor to fatality in this model. Alternatively (or additionally), accumulation of toxins elaborated by tumor cells throughout the brain starting early in the evolution of the tumor may also contribute to fatality.

Animals↗
PubMed1998

Sialic acid concentration of brain gangliosides: variation among eight mammalian species.

Sialic acid is a vital component of brain gangliosides which play an essential role in the transmission and storage of information in the brain. The concentration of bound sialic acid in gangliosides and free sialic acid in the brain cortex of eight different mammals [human, chimpanzee (Pan troglodytes), rat (Rattus norvegicus), mouse (Mus musculus), rabbit (Oryctolagus cuniculus), sheep (Ovis aries), cow (Bos indicus) and pig (Sus scrofa)] were compared. Total sialic acid concentration (890+/-103 microg/g wet weight tissue, mean+/-SE, n = 6) was 2-4 times higher in the human brain compared with the other species studied (0.001 < p < 0.05). There was no significant difference between human males and females. The rank order of adult brain sialic acid after humans (in microg/g) was rat (493+/-23, n = 12), mouse (445+/-29, n = 16), rabbit (380+/-18, n = 6), sheep (323+/-43, n = 6), cow (304+/-14, n = 6) and pig (252+/-14, n = 6). Apart from the cow vs the sheep, the differences between species were statistically significant (p < 0.05). In the mouse, cow and sheep, total sialic acid concentration increased during maturation by 18-32% (p < 0.05). In a 2-year-old chimpanzee, the sialic acid concentration in the left lobe of the brain cortex was 25% higher than that of right lobe at 6 weeks of age (p < 0.05). Free sialic acid was higher in the human brain cortex (41+/-3 microg/g) than that of the rat and mouse (32+/-3 and 25+/-5 microg/g respectively) and absent from other species. Variation in brain sialic acid concentration among different animals has implications for the evolution of the brain and may affect learning ability in animals.

Aging↗
PubMed1991

HIV-1 V3 domain variation in brain and spleen of children with AIDS: tissue-specific evolution within host-determined quasispecies.

DNA coding for the principal neutralization epitope of HIV-1 (the V3 domain of the envelope glycoprotein gp120) was amplified by polymerase chain reaction from postmortem brain and spleen tissue of three perinatally infected children who died of AIDS with progressive encephalopathy. Sequences obtained directly (without cloning) from this DNA were compared with sequences of 52 molecular clones made from this DNA. Cluster analysis showed that V3 domain sequences from two of the three children were similar to sequences from the American MN/SC isolates, while those from one child were more closely similar to the Caribbean RF isolate. Comparison of sequences obtained directly with consensus sequences derived from cloned DNA showed that V3 sequences are characteristic for an individual host. In one child, the V3 sequence determined directly from brain DNA was very distant from the consensus brain clone sequence and from the spleen sequences, suggesting a diverging quasispecies distribution. Site-directed hybridization demonstrated that brain-specific sequences present in 33% of brain-derived clones were absent from clones derived from spleen. The evidence suggests that brain- and spleen-specific variants evolve independently within each host-delimited quasispecies.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Evolution of primary microcephaly genes and the enlargement of primate brains.

Brain size, in relation to body size, has varied markedly during the evolution of mammals. In particular, a large cerebral cortex is a feature that distinguishes humans from our fellow primates. Such anatomical changes must have a basis in genetic alterations, but the molecular processes involved have yet to be defined. However, recent advances from the cloning of two human disease genes promise to make inroads in this important area. Microcephalin (MCPH1) and Abnormal spindle-like microcephaly associated (ASPM) are genes mutated in primary microcephaly, a human neurodevelopmental disorder. In this 'atavistic' condition, brain size is reduced in volume to a size comparable with that of early hominids. Hence, it has been proposed that these genes evolved adaptively with increasing primate brain size. Subsequent studies have lent weight to this hypothesis by showing that both genes have undergone positive selection during great ape evolution. Further functional characterisation of their proteins will contribute to an understanding of the molecular and evolutionary processes that have determined human brain size.

Animals↗
PubMed1999

The gospel of the fossil brain: Tilly Edinger and the science of paleoneurology.

Tilly Edinger (1897-1967) was a vertebrate paleontologist interested in the evolution of the central nervous system. By combining methods and insights gained from comparative neuroanatomy and paleontology, she almost single-handedly founded modern paleoneurology in the 1920s while working at the Senckenberg Museum in Frankfurt am Main. Edinger's early research was mostly descriptive and conducted within the theoretical framework of brain evolution formulated by O. C. Marsh in the late 19th century. Nevertheless, she became immediately known in 1929 after publishing an extensive review on "fossil brains." Reconstructing evolutionary history from the fossil record instead of from the comparative analysis of living forms allowed her to identify the sequence of neural innovations within several mammalian lineages. Anti-Jewish terrorism forced Edinger to leave Nazi Germany in 1939. After finding refuge first in England, she continued her career at Harvard's Museum of Comparative Zoology. There she documented the occurrence of gross neural correlates of specialized behavior in several vertebrate lineages, and identified parallel evolution in mammalian sulcation patterns. Her insight that neural innovations need not be "correlated" with either nonneural innovations or with evolutionary "success" led her to reject Marsh's theory of progressive increase in brain size over time and other "anthropocentric" understandings of brain evolution. Edinger's research, her insistence on a stratigraphic and evolutionary framework for interpretation, and her massive compilations of paleoneurological literature established her as the leading definer, practitioner, and chronicler of her field.

Brain↗
PubMed1976

The role of vascular proliferation in the growth of brain tumors.

The formation of new blood vessels, i.e., angiogenesis, is a critical step in the evolution of a brain tumor from the earliest avascular phase to the clinically overt, vascular stage. For cerebral astrocytomas, intense capillary proliferation is a poor prognostic sign, associated with rapidly growing tumors. The in vivo production of a vasoformative substance can be demonstrated by transplanting human and experimental gliomas to the rabbit cornea. Intense neovascularization is elicited by the tumor and not by control tissues. If the same tumor is transplanted to the vitreous, thereby interrupting the vasoformative signal, the tumor remains in a dormant state for a prolonged period of time, despite its malignant potential. Inhibition of angiogenesis would be an important adjunct to the surgical treatment of gliomas.

Animals↗
PubMed1988

Anatomical brain asymmetries in New World and Old World monkeys: stages of temporal lobe development in primate evolution.

Relatively large (n = 20-30) samples of formalin-fixed brain specimens from five Old and New World monkey species were examined in a study measuring anatomical temporal-lobe asymmetries. Linear measurements of the length of the Sylvian fissure were taken on each cerebral hemisphere to evaluate lateral differences related to development of auditory association cortex. The results indicate significantly greater Sylvian fissure length on the left hemisphere than on the right hemisphere in four of these species. Measurements of a different parameter on Saimiri sciureus brain specimens (length of anterior portion of the Sylvian fissure) also suggested temporal-lobe asymmetry favoring the left hemisphere. Other measurements (length of the Sylvian fissure lying posterior to the central sulcus, and dorso-ventral position of the Sylvian point) in Macaca mulatta and M. fascicularis did not reveal significant right/left-hemisphere differences. Sylvian-fissure length determined from photographs of M. mulatta hemispheres in contrast to results of direct measurements did not yield significant right/left-hemisphere asymmetry. We mention possible reasons why previous anatomical studies of brains from monkeys did not discern temporal-lobe asymmetry, and we also discuss whether or not certain of these asymmetries in monkeys foreshadowed the evolution of language-processing areas of the cerebral cortex in hominids.

Animals↗
PubMed1978

Intracranial pressure reserve testing. Initial clinical observations.

Sequential subdural injections of fluid through an intracranial pressure (ICP) monitoring cup catheter have been employed to measure "ICP reserve" in a series of 136 determinations in 30 patients over a total of 155 days of recordings. This dynamic method of quantitating the brain's ability to adapt to increased intracranial volume tests the brain's compensatory mechanisms over a five-minute time span. The test, incorporating several safety features, has been found to be reliable, safe, and well tolerated. A series of observations have been made using this test in patients with subdural drains and in response to fluid, mannitol, and dexamethasone therapy. Deteriorating ICP reserve gave early warning of the need for reoperation for postoperative hematoma, massive brain swelling, or cystic reaccumulation. Intracranial pressure reserve testing also quantitated the evolution of postoperative brain edema. Changes in ICP reserve could be detected as much as 48 hours before changes in baseline ICP and as much as 72 hours before clinical deterioration was evident.

Brain↗