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At least 757 records · Page 42Linked to original sources
PubMed2002

Immunology of viral-vector-mediated gene transfer into the brain: an evolutionary and developmental perspective.

The immune system imposes limitations on gene transfer into the brain. Viral vectors injected into the brain's ventricular system elicit innate and adaptive immune responses. However, when injected directly into the brain parenchyma, they elicit only transient inflammation owing to the absence of dendritic cells, which transport antigen to lymph nodes and present it to naive T cells to initiate adaptive immune responses. This article explores the evolutionary and developmental basis of brain immune responses and their implications for viral-vector-mediated neurological gene therapy. Elucidating the cellular and molecular basis of these differential reactions is essential to the long-term success of neurological gene therapy.

Animals↗
PubMed2006

Contrasting evolution of expression differences in the testis between species and subspecies of the house mouse.

Regulatory changes in genes involved in reproduction are thought to be prime targets for divergence during speciation, since they are expected to play an important role in sexual selection and sexual conflict. We used microarray analysis of RNA from different wild populations of house mouse subspecies (including Mus m. musculus, Mus m. domesticus, and Mus m. castaneus) and from the sister species Mus spretus to test this assumption. A comparison of expression divergence in brain, liver/kidney, and testis shows a major difference in the evolutionary dynamics of testis-related genes. While the comparison between species confirms an excess in divergence in testis genes, we find that all comparisons between subspecies yield only a very small number of genes with significantly different expression levels in the testis. These results suggest that the early phase of the speciation process may not be driven by regulatory changes in genes that are potential targets of sexual selection, and that the divergence in these genes is only established during a later phase of the speciation process.

Animals↗
PubMed1975

The language capability of Neanderthal man.

Considerable publicity has been given a recent article by Lieberman and Crelin ('71) which argues that Neanderthal man lacked the physical features necessary for speech. This present paper presents statistics on some modern men with normal speech who show physical features in common with Neanderthal man. The brain of Neanderthal man was as large as, or larger than, that of modern man. The brain reflected by endocranial cast of the La Chapelle-aux-Saints skull resembles that of modern man in an area important for speech and therapy suggests Neanderthal man had the neural development necessary for language.

Achondroplasia↗
PubMed1996

Localization and characterization of neuropeptide Y/peptide YY receptors in the brain of the smooth dogfish (Mustelis canis).

Multiple receptor subtypes specific for the neuropeptide Y (NPY)/peptide Y (PYY) family of peptides exist in mammals, but little is known about the distribution of this receptor family in other vertebrates. Saturable binding sites for 125I-labeled porcine PYY were localized in frozen sections of the brain of the smooth dogfish (Mustelis canis) by radioligand binding and autoradiography. Saturable 125I-porcine PYY binding sites were distributed widely in the cerebral hemispheres, optic lobes, hypothalamus, cerebellum and hindbrain. Binding was saturable, specific for PYY and related peptides, and of high affinity (Kd = 2.53 nM). The specificity of the binding site was analyzed by performing competitive inhibition experiments with nonradioactive PYY, NPY, and [Leu31, Pro34]-NPY and NPY13-36, synthetic peptide analogs specific for the mammalian Y1 and Y2 receptor subtypes, respectively. Saturable 125I-porcine PYY binding sites in all regions of the dogfish brain closely resembled the mammalian Y1 NPY receptor subtype in specificity for these substances. There was no evidence for expression of multiple receptor subtypes. We conclude that a single receptor specific for the NPY/PYY family of peptides is widely expressed in the smooth dogfish brain and that this receptor closely resembles the mammalian Y1 receptor subtype, suggesting that the Y1 receptor is the ancestral receptor in this family.

Animals↗
PubMed2006

Is Huntington's a glutamine storage disease?

Huntington's disease is a neurological disorder caused by the expansion of a polyglutamine tract in the protein huntingtin. Several other neurological diseases also result from the expansion of polyglutamine regions in different proteins. Despite intense efforts, no definitive biochemical or physiological role for huntingtin has been described, nor has a function been assigned to the polyglutamine region in unaffected individuals. This article presents the hypothesis that polyglutamine expansions within huntingtin and other polyglutamine proteins provide a function in and of themselves. Incorporating multiple glutamine residues into a protein during synthesis, and releasing them during protein turnover, may represent a means of minimizing interruptions in brain levels of glutamine and glutamate during periods of malnutrition. The number and variety of different proteins containing polyglutamine expansions can be interpreted as a series of evolutionary "experiments" toward a nontoxic form for glutamine storage.

Animals↗
PubMedDate not supplied

[Nonspecific brain structures and specialization in the central nervous system].

It has been demonstrated that corticofugal influences may exert selective control of single sensory signals which converge on the neurons of the striatum and other non-specific structures of the brain. This finding suggests that complex sensory image may be formed not by assembling separate elementary signals, but rather by a selective control of these signals into a total sensory inflow within the network brain structures. This conclusion is confirmed by comparative anatomical data. In the phylogenesis of vertebrates, brain structures differentiate presumably into both the specific ones which perform the analysis of only the given kind of information, and those (conventionally described as non-specific) which are specialized on sensory integration and exhibit functional polymodality.

Animals↗
PubMed1998

Brain and conscious experience.

There is a deep belief that we can attain not only a neuroscience of consciousness but a neuroscience of human consciousness. It is as if something terribly new and complex happens as the brain enlarges to its human form. Whatever this is, it triggers our capacity for self-reflection, for ennui, and for lingering moments, I would like to propose a simple, three-step suggestion. First, we should focus on what we mean when we talk about conscious experience. It is merely the awareness we have of our capacities as a species, but not the capacities themselves--only the awareness or feelings we have about them. The brain is clearly not a general purpose computing device but is a collection of circuits devoted to quite specific capacities. This is true for all brains, but what is wonderful about the human brain is that we have untold numbers of these capacities. We have more than the chimp, which has more than the monkey, which has more than the cat, which runs circles around the rat. Because we have so many specialized systems and because they can frequently do things they were not designed to do, it appears our brains have a single, general computing device. But we do not. Thus, step 1 requires that we recognize we are a collection of adaptations and, furthermore, we recognize the distinction between a species' capacities and its feelings about those capacities. Now consider step 2. Can there be any doubt that a rat at the moment of copulation is as sensorially fulfilled as a human? Of course it is. Do you think a cat does not enjoy a good piece of cod? Of course it does. Or, a monkey does not enjoy a spectacular swing? Again, it has to be true. Each species is aware of its special capacities. So, what is human consciousness? It is the very same awareness, save for the fact that we can be aware of so much more, so many wonderful things. A circuit--perhaps a single system or one duplicated over and over again--is associated with each brain capacity. The more systems a brain possesses, the greater the awareness of capacities. Think of the variations in capacity within our own species; they are not unlike the vast differences between species. Years of split-brain research have informed us that the left hemisphere has many more mental capacities than the right one. The left is capable of logical feats that the right hemisphere cannot manage. Although the right has capacities such as facial recognition systems, it is a distant second with problem-solving skills. In short, the right hemisphere's level of awareness is limited. It knows precious little about a lot of things, but the limits to human capacity are everywhere in the population. No one need be offended to realize that just as someone with normal intelligence can understand Ohm's law, others, like yours truly, are clueless about Kepler's laws. I am ignorant about them and will remain so. I am unable to be aware about what they mean for the universe. The circuits that enable me to understand these things are not present in my brain. By emphasizing specialized circuits that arise from natural selection, we see that the brain is not a unified neural net that supports a general problem-solving device. With this being understood, we can concentrate on the possibility that smaller, more manageable circuits produce awareness of a species' capacities. Holding fast to the notion of a unified neural net means we can understand human conscious experience only by figuring out the interactions of billions of neurons. That task is hopeless. My scheme is not. Hence step 3. The very same split-brain research that exposed shocking differences between the two hemispheres also showed that the human left hemisphere has the interpreter. The left brain interpreter's job is to interpret our behavior and our responses, whether cognitive or emotional, to environmental challenges. It constantly establishes a running narrative of our actions, emotions, thoughts, and dreams. It is the glue that keeps our

Animals↗
PubMed1984

[Purification and characterization of glutamine synthetase from chicken brain].

A procedure for the isolation and purification to homogeneity of glutamine synthetase (E.C. 6.3.1.2.) from chick brain is described. The physico-chemical properties of the purified enzyme preparation are similar to those of other eucaryotic glutamine synthetases. The optimum activity of glutamine synthetase is dependent on the Mg++ to ATP ratio in the reaction mixture rather than on the magnesium or ATP concentrations. The characteristics of the enzyme studied through various phylogenetic trees suggest that this enzyme is preserved during evolution.

Animals↗
PubMed1996

The molecular composition of neuronal microfilaments is spatially and temporally regulated.

The actin-based microfilament system is thought to play a critical role in neuronal development. We have determined specific changes in the composition of microfilaments accompanying neuronal morphogenesis. By using specific antibodies against the isoforms for tropomyosin (Tm) (Tm-5 and TmBr-1/-3) and actin (beta- and gamma-actin), we found that during early morphogenesis in vivo immature growing axons contain beta- and gamma-actin and Tm-5. In particular, Tm-5 is exclusively located in the immature axonal processes relative to the neuronal cell body. In contrast, beta-actin and Tm-5 are absent in mature, quiescent axons. This developmental loss from axons is associated with an approximately twofold downregulation of beta-actin and Tm-5 levels in the brain; gamma-actin levels do not change, and this molecule is widely distributed throughout neurons during development. The loss of beta-actin and Tm-5 from axons is accompanied by a progressive appearance of TmBr-1/-3. This apparent replacement of Tm-5 with TmBr-1/-3 occurs over a 2 d time period during rat embryonic hindbrain development and is conserved in evolution between birds and mammals. The loss of Tm-5 from axons involves a redistribution of this molecule to the cell soma and dendrites. These findings suggest that specialized microfilament domains are associated with the development and maintenance of neuronal polarity. We conclude that these Tm isoforms and beta-actin are subject to specific patterns of segregation associated with axonal development and neuronal differentiation. This provides a potential molecular basis for the temporal and spatial specificity of microfilament function during neuronal differentiation.

Actin Cytoskeleton↗
PubMed2000

Organization of sensory cortex in the East African hedgehog (Atelerix albiventris).

We investigated the organization of neocortex in the East African hedgehog (Atelerix albiventris) with microelectrode recordings from sensory areas that were later correlated with cytochrome oxidase patterns in sections of flattened cortex. The location of corticospinal projecting neurons was also examined and related to sensory areas by making small injections of wheat germ agglutinin-horseradish peroxidase into the spinal cord. Our goals were to determine how hedgehog cortex is organized, how much sensory areas overlap, and to compare results with recent findings in other insectivores. Evidence was found for three separate topographically organized somatosensory areas, two visual areas, and a caudolateral auditory area. A medial somatosensory area corresponded to S1, the primary somatosensory area, whereas two lateral areas partially encircled auditory cortex and corresponded to the parietal ventral area (PV) and the secondary somatosensory area (S2). Primary visual cortex (V1) was delineated by a caudomedial cytochrome oxidase dark oval, and a more lateral visual area between V1 and somatosensory cortex corresponded to V2, or area 18. Two patches of corticospinal projecting cells were found primarily overlapping S1 and S2. Some bimodal auditory and somatosensory responses were found in parts of PV and S2, but for the most part, areas had relatively sharp histochemically apparent and physiologically defined borders. The present results indicate that the caudal neocortex of hedgehogs has only a few sensory areas, corresponding to those commonly found in several other small-brained mammals. Hedgehog cortical organization differs significantly in somatotopy, number, and position of fields from that of closely related shrews and moles. Thus, clear specializations occur, even within the order Insectivora.

Animals↗
PubMed2005

The motivation to control and the origin of mind: exploring the life-mind joint point in the Tree of Knowledge System.

The evolved function of brain, cognitive, affective, conscious-psychological, and behavioral systems is to enable animals to attempt to gain control of the social (e.g., mates), biological (e.g., prey), and physical (e.g., nesting spots) resources that have tended to covary with survival and reproductive outcomes during the species' evolutionary history. These resources generate information patterns that range from invariant to variant. Invariant information is consistent across generations and within lifetimes (e.g., the prototypical shape of a human face) and is associated with modular brain and cognitive systems that coalesce around the domains of folk psychology, folk biology, and folk physics. The processing of information in these domains is implicit and results in automatic bottom-up behavioral responses. Variant information varies across generations and within lifetimes (e.g., as in social dynamics) and is associated with plastic brain and cognitive systems and explicit, consciously driven top-down behavioral responses. The fundamentals of this motivation-to-control model are outlined and links are made to Henriques' (2004) Tree of Knowledge System and Behavioral Investment Theory.

Animals↗
PubMedDate not supplied

[Brain lipids of a mammoth, Elephas primigenius, which died more than 40,000 years ago].

Studies have been made on the brain lipids of the 6--7-month mammoth which remained in the eternal ice for more than 40.000 years. Thin layer chromatography of chloroformmethanol extract of the brain lipids shows that all glycerophospholipids in the brain were destroyed. On the contrary, sphingophospholipid sphingomyelin yielded the evident spot which was identified by specific reactions and by comparison with sphingomyelin from the brain of rat. Sphingomyelin content was evaluated. Using gas-liquid chromatography, fatty acid composition of sphingomyelin was investigated. It was found to be close to that in contemporary mammals. Other shingolipids -- cerebrosides, sulfatides, gangliosides -- persisted (probably, only partially) and were studied quantitatively. Relative content of cerebrosides with normal fatty acids and hydrooxyacids was determined. Studies were also made on fatty acid composition of cerebrosides, sulfatides and gangliosides, as well as on the composition of spingosine bases of gangliosides. Free cholesterol was found in the brain of the mammoth. Other sterols were not detected. With respect to quantitative evaluation of the preserved lipids, it should be mentioned that on the one hand, the brain underwent dehydration which increased lipid content per a unit of "wet" weight, whereas on the other one lipids were partially degraded, this process decreasing their content.

Animals↗
PubMedDate not supplied

[Comparative biochemical study of brain phospholipids in insects].

Studies have been made on the content of total phospholipids (PL) and their separate families in the brain of larvae and imago of the insect species Blaberus giganteus, Periplaneta americana, Tenebrio molitor and Barathra brassicae. It was shown that during larval-pupal-imaginal transformation in T. molitor and B. brassicae the content of total PL increases by 17 and 14% respectively, whereas in B. giganteus and P. americana PL concentration undergoes only insignificant changes. With respect to total PL content the species investigated form the following sequence: B. brassicae greater than T. molitor greater than P. americana greater than B. giganteus. In larval and imago forms of these insects phosphatidylethanolamine, phosphatidylcholine, phosphatidylserine, phosphatidylinositol, sphingomyelin and polyglycerophosphatide were found in the brain. Besides, in the brain of B. giganteus and P. americana lysophosphatidylethanolamine and in the brain of T. molitor -- phosphatidic acid are present. Qualitative PL composition in larval and imago forms is identical, while quantitative ratio of separate fractions differs insignificantly. In all the species investigated, phosphatidylethanolamine and phosphatidylcholine are the most abundant phospholipids.

Animals↗
PubMedDate not supplied

Bioassayable cholecystokinin in the brain of the goldfish, Carassius auratus.

Cholecystokinin (CCK)-gastrin peptides are shown to be present in the brain of all the species ranging from coelenterates to mammals. Differentiation between CCK and gastrin, presumed to be evolved from a common ancestral cerulein-like peptide, has been suggested to occur at the level of the amphibians. We examined the presence of bioassayable CCK, as determined by its potency to stimulate enzyme secretion from isolated rat pancreatic acini, in the brain of the goldfish Carassius auratus, a more primitive vertebrate than the amphibian. Among the various regions tested, the brain stem, telencephalon and spinal cord possess the highest levels of bioassayable CCK followed in decreasing order by gustatory lobes, optic tectum and duodenum. No detectable levels of CCK were found in the cerebellum. The observed bioactivity was not due to gastrin because: radioimmunoassay of the brain homogenates for gastrin revealed very low or nondetectable levels of gastrin; amylase release dose-response curves for standard CCK8 and the brain homogenate were identical; and proglumide, a competitive antagonist of CCK8, inhibited homogenate CCK-induced enzyme release with a parallel rightward shift in the dose-response curve. These observations provide evidence for the distinct presence of CCK in the brain of the goldfish suggesting that the differentiation of CCK as a distinct neuropeptide, from that of gastrin, occurs at the level of Osteichthyes (bony fish).

Amino Acid Sequence↗
PubMed2004

PXR (NR1I2): splice variants in human tissues, including brain, and identification of neurosteroids and nicotine as PXR activators.

To gain insight on the expression of pregnane X receptor (PXR), we analyzed PXR.1 and PXR alternatively spliced transcripts in a panel of 36 human tissues. PXR.1 was expressed in many more tissues than previously determined, including human bone marrow and select regions of the human brain. In each of these tissues, we observed alternative splicing of various exons of PXR that generated multiple distinct PXR isoforms. The most abundant PXR alternative mRNA transcripts lacked 111 nucleotides, deleting 37 amino acids from the PXR LBD (PXR.2), or lacked 123 nt, deleting 41 amino acids from the PXR LBD (PXR.3). CYP3A4, a gene transcriptionally regulated by PXR, showed incomplete overlap with PXR in its tissue distribution. Quantitation of PXR mRNAs in human liver demonstrated that PXR.2 and PXR.3 represented 6.7% and 0.32% of total PXR mRNA transcripts. Brain expression of PXR prompted analysis of whether some brain acting chemicals were PXR ligands. The neurosteroids allopregnanolone and pregnanolone activated PXR and induced transcription of a CYP3A4-luciferase reporter. Nicotine, the psychoactive and addictive chemical in cigarettes, and a known inducer of brain CYP2B6, was an efficacious activator of PXR and inducer of CYP3A4 transcription. Because nicotine activation of PXR will enhance metabolism of nicotine to the non-psychoactive cotinine, these results provide one molecular mechanism for the development of tolerance to nicotine. Moreover, the identification of PXR in many human tissues, such as brain, and activation by tissue specific ligands (such as neurosteroids) suggests additional biological roles for this receptor in these tissues.

Adult↗
PubMed1995

Functional constraints against variations on molecules from the tissue level: slowly evolving brain-specific genes demonstrated by protein kinase and immunoglobulin supergene families.

In the protein kinase family, the basic function of kinase domain is similar among members. According to the standard view of functional constraint, the molecular evolutionary rate depends on functional and structural features characteristic of individual molecules (local constraint). Thus the evolutionary rate of the kinase domain is expected to be similar for different members. Contrary to this expectation, a comparison of the evolutionary rates revealed a wide difference among members; it amounts to about 100 times difference between the maximum and minimum rates. A similar result was also found in members of the immunoglobulin (Ig) family. In addition, significant correlations in evolutionary rate were observed between the kinase domain and the Ig-like domain in the receptor protein tyrosine kinases and between the kinase domain and the SH domain in the nonreceptor-type kinases. Furthermore, the evolutionary rates of family members that are expressed tissue specifically differ widely, depending on their tissue distribution: members expressed in the brain evolve with significantly slower rates than those expressed in the immune system. These results strongly suggest the presence of an alternative constraint (global constraint) against changes on molecules derived from higher levels like tissues or organs.

Animals↗
PubMed2004

Reduction of brain and sense organs in the fossil insular bovid Myotragus.

Our study of the fossil rupicaprine bovid Myotragus [Bate, 1909] from the Mediterranean island Majorca (Spain) provides evidence that this animal underwent significant changes (reduction) in the relative size of brain and sense organs after geographic isolation at the end of the Messinian Salinity Crisis (Miocene-Pliocene boundary, 5.2 Mya). The changes in the central nervous system of Myotragus parallel the pattern reported for domesticated animals, in which decrease in relative brain size is accompanied by a decrease in the relative size of their sense organs. We interpret the important size reduction of brain and sense organs in Myotragus as an adaptive strategy for more efficient energy use under the special environmental conditions of the insular ecosystem, characterized by absence of predation and limitation of trophic resources.

Animals↗