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The hypothesis of a possible cure for death by means of humanmade brains or brain-like machines, recently published in this journal, is briefly discussed and some questions are raised. The possibility that death may be naturally reversible is then considered.
Two receptors (CKA and CKB) of the G protein-coupled melatonin receptor family were cloned from chick brain. CKA encodes a protein that is 80% identical at the amino acid level to the human Mel1a melatonin receptor and is thus designated the chick Mel1a melatonin receptor. CKB encodes a protein that is 80% identical to the Xenopus melatonin receptor and defines a new receptor subtype, the Mel1c melatonin receptor, which is distinct from the Mel1a and Mel1b melatonin receptor subtypes. A melatonin receptor family consisting of three subtypes is supported by PCR cloning of distinct melatonin receptor fragments from Xenopus and zebrafish. Expression of CKA and CKB results in similar ligand binding and functional characteristics. The widespread distribution of CKA and CKB mRNA in brain provides a molecular substrate for the profound actions of melatonin in birds.
The neuropsychology of religious activity in normal and selected clinical populations is reviewed. Religious activity includes beliefs, experiences, and practice. Neuropsychological and functional imaging findings, many of which have derived from studies of experienced meditators, point to a ventral cortical axis for religious behavior, involving primarily the ventromedial temporal and frontal regions. Neuropharmacological studies generally point to dopaminergic activation as the leading neurochemical feature associated with religious activity. The ventral dopaminergic pathways involved in religious behavior most closely align with the action-extrapersonal system in the model of 3-D perceptual-motor interactions proposed by . These pathways are biased toward distant (especially upper) space and also mediate related extrapersonally dominated brain functions such as dreaming and hallucinations. Hyperreligiosity is a major feature of mania, obsessive-compulsive disorder, schizophrenia, temporal-lobe epilepsy and related disorders, in which the ventromedial dopaminergic systems are highly activated and exaggerated attentional or goal-directed behavior toward extrapersonal space occurs. The evolution of religion is linked to an expansion of dopaminergic systems in humans, brought about by changes in diet and other physiological influences.
Previous research has shown orexin/hypocretin immunoreactive (orexin-ir) neurons in domesticated Galliformes. However, these findings may not be representative of other birds and these studies did not include a distribution of orexin-ir projections throughout the brain. The present study was carried out in a wild-caught passerine, the house finch, Carpodacus mexicanus, and includes a detailed description of orexin-ir neurons and their projections. Orexin A and B-ir neurons were located in a single population centered on the paraventricular nucleus of the hypothalamus extending into the lateral hypothalamic area, consistent with other studies in birds. Orexin A and B-ir fibers were similarly visible across the brain, with the highest density within the preoptic area, hypothalamus and thalamus. Orexin-ir projections extended from the paraventricular nucleus rostrally to the preoptic area, laterally towards the medial striatum, nidopallium, and dorsally along the lateral ventricle towards the mesopallium. Caudally, the highest densities of orexin-ir fibers were found along the third ventricle. The periaqueductal grey, substantia nigra pars compacta and the locus coeruleus also showed a high density of orexin-ir fibers. This study showed a detailed fiber distribution previously unreported in birds and showed that orexin-ir neurons were located in similar areas regardless of phylogeny or domestication in birds. The apparently conserved neural distribution of orexins suggests that these peptides play similar roles among birds. The widespread distribution of the projections in brain areas serving various roles indicates the potential involvement of these peptides in multiple behavioral and physiological functions.
On the basis of a description of an endocast from Hadar early hominid AL 162-28, it has been suggested that cerebral organization towards a human pattern occurred as early as 3-4 Myr ago. I have studied a cast of the AL 162-28 calvaria and a copy of an endocast prepared from the original fossil, and report here observations regarding cranial capacity, the relationship between endocast and skull, sulcal pattern, brain shape and cranial venous sinuses. Contrary to the earlier report, all of these features appear to be consistent with an ape-like external cortical morphology in Hadar early hominids and in my view there is no evidence for expansion or reorganization of parietal/occipital regions. Cranial capacity of AL 162-28 is at least 10% and 29% smaller than respective mean capacities of subsequently living gracile and robust australopithecines, who also exhibit ape-like cortical patterns. Thus palaeoneurological evidence from the entire early hominid record suggests that the trend towards brain enlargement preceded cortical reorganization.
Heterologous radioimmunoassays (RIAs) for the mammalian prodynorphin end products, alpha-neo-endorphin, dynorphin A(1-17), dynorphin A(1-8), and dynorphin B(1-13) were used to screen brain extracts obtained from representatives of the major surviving orders of reptiles: Chelonia (Pseudemys scripta), Squamata (Anolis carolinensis), and Crocodylia (Alligator mississippiensis). Methanol/acid extracts of whole brains obtained from each species were separately fractionated by gel filtration chromatography and reversed-phase HPLC. In all three species, an immunoreactive form of alpha-neo-endorphin was detected with the same retention time as synthetic mammalian alpha-neo-endorphin following reversed-phase HPLC analysis. In all three species, reversed-phase HPLC analysis revealed a novel form of dynorphin B(1-13)-related immunoreactivity. With the available immunological probes, dynorphin A products were only detected in the Anolis brain extracts. Both dynorphin A(1-17) and dynorphin A(1-8) were detected in this species.
For parallel computers to simulate our brains, we must face the fact that human beings have a better claim on the title Homo seriatim than Homo sapiens--we're more consistently serial than wise.
Although humans and their closest evolutionary relatives, the chimpanzees, are 98.7% identical in their genomic DNA sequences, they differ in many morphological, behavioral, and cognitive aspects. The underlying genetic basis of many of these differences may be altered gene expression. We have compared the transcriptome in blood leukocytes, liver, and brain of humans, chimpanzees, orangutans, and macaques using microarrays, as well as protein expression patterns of humans and chimpanzees using two-dimensional gel electrophoresis. We also studied three mouse species that are approximately as related to each other as are humans, chimpanzees, and orangutans. We identified species-specific gene expression patterns indicating that changes in protein and gene expression have been particularly pronounced in the human brain.
Melatonin binding sites were identified in the brain and retina of the lizard Anolis carolinensis using in vitro autoradiography. Radioactive labeling was observed in areas which receive primary, secondary, and tertiary visual input: the superficial layers of the optic tectum, lateral geniculate nucleus, nucleus rotundus, dorsal ventricular ridge, and striatum. Other areas that demonstrated binding included the left medial habenular nucleus, the interpeduncular nucleus, medial cortex, dorsal cortex, mammillary nucleus, and septum. In the retina, melatonin binding was localized in the inner plexiform layer. Radioactive melatonin binding to the optic tectum was reduced in the presence of a nonhydrolyzable cyclic GMP analog, indicating that the melatonin receptor in the brain of this lizard is associated with a G-protein. These results suggest that melatonin receptor binding sites are widely distributed in the forebrain and midbrain of the iguanid lizard, and are prominent in areas of the nervous system that are associated with visual processing. The highest degree of melatonin binding appeared in the left medial habenular nucleus, interpeduncular nucleus, and dorsal ventricular ridge. This suggests that these brain regions may be important targets for the actions of melatonin, such as its effects on circadian rhythmicity, thermoregulation and photoperiodic reproduction.
According to the social intelligence hypothesis, relative neocortex size should be directly related to the degree of social complexity. This hypothesis has found support in a number of comparative studies of group size. The relationship between neocortex and sociality is thought to exist either because relative neocortex size limits group size or because a larger group size selects for a larger neocortex. However, research on primate social evolution has indicated that male and female group sizes evolve in relation to different demands. While females mostly group according to conditions set by the environment, males instead simply go where the females are. Thus, any hypothesis relating to primate social evolution has to analyse its relationship with male and female group sizes separately. Since sex-specific neocortex sizes in primates are unavailable in sufficient quantity, I here instead present results from phylogenetic comparative analyses of unsexed relative neocortex sizes and female and male group sizes. These analyses show that while relative neocortex size is positively correlated with female group size, it is negatively, or not at all correlated with male group size. This indicates that the social intelligence hypothesis only applies to female sociality.
In all vertebrate species examined thus far the production of new neurons in the central nervous system takes place not only during embryogenesis but also in adult life. However, although in mammals this so-called adult neurogenesis appears to be limited to a very few brain regions, in non-mammalian vertebrates new neurons are generated continuously in many regions of the adult central nervous system. This difference makes it particularly interesting to examine adult neurogenesis from a comparative point of view. Such an approach is likely not only to yield new insights into the evolution and function(s) of this phenomenon, but also to facilitate identification of central sites that, although quiescent in vivo, have retained their intrinsic potential to produce new cells during adulthood in mammals.
Wilson disease is an autosomal recessive disorder of copper transport. Disease symptoms develop from the toxic build-up of copper primarily in the liver, and subsequently in the brain, kidney, cornea and other tissues. A candidate gene for WD (ATP7B) has recently been identified based upon apparent disease-specific mutations and a striking amino acid homology to the gene (ATP7A) responsible for another human copper transport disorder, X-linked Menkes disease (MNK). The cloning of WD and MNK genes provides the first opportunity to study copper homeostasis in humans. A preliminary analysis of the WD gene is presented which includes: isolation and characterization of the 5'-end of the gene; construction of a genomic restriction map; identification of all 21 exon/intron boundaries; characterization of extensive alternative splicing in brain; prediction of structure/function features of the WD and MNK proteins which are unique to the subset of heavy metal-transporting P-type ATPases; and comparative analysis of the six metal-binding domains. The analysis indicates that WD and MNK proteins belong to a subset of transporting ATPases with several unique features presumably reflecting their specific regulation and function. It appears that the mechanism of alternative splicing serves to regulate the amount of functional WD protein produced in brain, kidney, placenta, and possibly in liver.
Relative brain size and the relative size of six brain regions (main olfactory bulbs, accessory olfactory bulbs, telencephalon, optic tectum, cerebellum and brain stem) in ten species of anurans from five habitats were examined to determine whether there was any evidence of adaptation in brain structure. A previously published data set was also reanalysed. Arboreal frogs have larger body-size corrected brains than frogs from other habitats. Arboreal ranid (Platymantis vitiensis) and hylid (Hyla versicolor) possess slightly larger cerebella than the ranids and hylids from other habitats. Platymantis vitiensis lacks an accessory olfactory bulb. The fully-aquatic Xenopus laevis (Pipidae) has a smaller optic tectum and cerebellum than the non-fossorial hylids and ranids. Adaptation to life underground appears to explain the modified brains of two fossorial frogs, Hemisus guineensis (Ranidae) and Rhinophrynus dorsalis (Rhinophrynidae). Both species of fossorial frogs have reduced optic tecta, larger main olfactory and smaller accessory olfactory bulbs, and larger torus semicircularis than non-fossorial species. Our data showed a strong negative correlation between the size of the optic tectum and the size of the main olfactory bulbs. We conclude that, although anuran brains are very similar across taxa in qualitative and general structure, there are some interesting, apparent adaptations, to fossorial and arboreal life.
The distribution of cholinergic neurons was studied in painted and red-eared turtles using antisera against choline acetyltransferase (ChAT). The results showed that the organization of cholinergic systems in the central nervous system of turtles was remarkably similar to that previously described in diverse other species. For example, the present studies revealed the presence of cholinergic neurons in the striatum, the basal telencephalon, the isthmo-tectal system, and a region of cells near the cerebellar peduncle. The motoneurons of the III, IV, V, VI, VII, X and XII cranial nerves and the spinal ventral horn were also shown to be cholinergic. Additional cholinergic neurons were observed in the hypothalamus and rhombencephalic reticular formation. These results help to clarify the precise extent and location of the major cholinergic cell groups of the turtle brain, thereby adding to our understanding of the organization of the turtle nervous system. The results also reveal that the cholinergic systems of the striatum, basal forebrain, isthmic region, and cerebellar peduncular region are ancestral features of the amniote brain and are common to all living amniotes that have been studied. Thus, the organization and, presumably, the function of the cholinergic systems appear to be conservative.
In the last 30 years, while considerable progress has been made in laboratory research of malignant gliomas, fewer clinical breakthroughs can be highlighted. Laboratory research has improved our understanding of the biology, and especially the molecular genetics of this disease. Unfortunately, these successes highlight the difficulties in translating laboratory results into substantive clinical improvements. In part, these difficulties stem from a schizophrenic view of the development and evolution of brain tumors. We believe either that (1) brain tumors are local and therefore the most important research should have as its goal local control, or (2) brain tumors are diffuse, which is to say that the cells rapidly grow beyond their initial locus, and our research goal is the prevention or treatment of the advancing tumor front. Clearly both hypotheses have merit and, in fact, almost certainly, both are true. The question becomes, should we devote our research energies to one hypothesis at the exclusion of the other?
Microcephalin gene is one of the major players in regulating human brain development. It was reported that truncated mutations in this gene can cause primary microcephaly in humans with a brain size comparable with that of early hominids. We studied the molecular evolution of microcephalin by sequencing the coding region of microcephalin gene in humans and 12 representative non-human primate species covering great apes, lesser apes, Old World monkeys and New World monkeys. Our results showed that microcephalin is highly polymorphic in human populations. We observed 22 substitutions in the coding region of microcephalin gene in human populations, with 15 of them causing amino acid changes. The neutrality tests and phylogenetic analysis indicated that the rich sequence variations of microcephalin in humans are likely caused by the combination of recent population expansion and Darwinian positive selection. The synonymous/non-synonymous analyses in primates revealed positive selection on microcephalin during the origin of the last common ancestor of humans and great apes, which coincides with the drastic brain enlargement from lesser apes to great apes. The codon-based neutrality test also indicated the signal of positive selection on five individual amino acid sites of microcephalin, which may contribute to brain enlargement during primate evolution and human origin.
Tumor microvessels differ in structure and metabolic function from normal vasculature, and neoangiogenesis is associated with quantitative and qualitative changes in expression of endothelial proteins. Such molecules could serve as molecular addresses differentiating the tumor vasculature from those of the normal brain. We have applied Systematic Evolution of Ligands by EXponential enrichment (SELEX) against transformed endothelial cells as a complex target to select single-stranded DNA-ligands (aptamers) that function as histological markers to detect microvessels of rat experimental glioma, a fatal brain tumor that is highly vascularized. Both the SELEX selection procedure as well as subsequent deconvolution-SELEX were analyzed by fluorescence based methods (flow cytometry and fluorescence microscopy). Of 25 aptamers analyzed, one aptamer was selected that selectively bound microvessels of rat brain glioblastoma but not the vasculature of the normal rat brain including peritumoral areas. The molecular target protein of aptamer III.1 was isolated from endothelial cells by ligand-mediated magnetic DNA affinity purification. This protein was identified by mass spectrometry as rat homologue of mouse pigpen, a not widely known endothelial protein the expression of which parallels the transition from quiescent to angiogenic phenotypes in vitro. Because neoangiogenesis, the formation of new blood vessels, is a key feature of tumor development, the presented aptamer can be used as a probe to analyze pathological angiogenesis of glioblastoma. The presented data show that pigpen is highly expressed in tumor microvessels of experimental rat brain glioblastoma and may play an important role in warranting blood supply, thus growth of brain tumors.
A multivariate analysis of 9 brain indices from 83 teleost species showed a marked opposition between the non-olfactory telencephalon (and diencephalon) and the medulla oblongata (phylogenetic characters) and between the olfactory bulbs and the optic tectum (adaptive characters). Results of three different classifying algorithms allowed determination of 6 stable groupings and 9 intermediate ones, some with systematic importance and some purely adaptive. For this reason brain organization criteria must be used with precaution for systematic purposes. Nevertheless, the position of Brotula multibarbata showed that this fish is an evolved acanthopterygian.