Increased Brain Mass Research Articles

Exploring the effects of moxibustion on cognitive function in rats with multiple cerebral infarctions from the perspective of glial vascular unit repairing

ObjectiveThis study aimed to explore the effect of moxibustion at Governor Vessel (GV) acupoints, including Baihui (GV 20), Shenting (GV 24) and Dazhui (GV 14) for 14 days on glial vascular unit (GVU) in rats with multiple microinfarctions (MMI), and to explore its action mechanism.MethodsThe effect and mechanism of moxibustion on vascular dementia (VD) were studied in MMI rats by means of behavioral and molecular biology experiments.ResultsRats receiving MMI showed impairment of memory function, reduction of cerebral blood flow, damage of blood-brain barrier (BBB) integrity and increased brain mass. MMI also increased neuronal degeneration in the hippocampus. Notably, levels of glial fibrillary acidic protein (GFAP) and complement component 3 significantly increased, but those of Connexin43 (CX43) and platelet derived growth factor receptor β (PDGFRβ) significantly decreased in the hippocampus of the rats receiving MMI. Moxibustion, as well as oxiracetam (ORC) treatment improved memory function and neuronal degeneration, ameliorated BBB integrity, increased cerebral blood flow and decreased brain mass. In addition, moxibustion as well as oxiracetam (ORC) treatment reduced the decrease of CX43 protein and increased PDGFRβ protein level in the hippocampus of MMI rats. Moreover, moxibustion treatment reversed MMI-induced increase of the GFAP/CX43 ratio in vascular structural units. Importantly, after PDGFRβ inhibition, VD rats treated with moxibustion had impaired learning and memory, decreased cerebral blood flow, and BBB disruption.ConclusionMoxibustion treatment at various GV acupoints improved cerebral blood flow and repaired BBB function in rats with MMI, likely through protecting GVU.

Altered cerebrovascular regulation in low birthweight swine

Full-term low birthweight (LBW) offspring exhibit peripheral vascular dysfunction in the postnatal period; however, whether such impairments extend to the cerebrovasculature remains to be elucidated. We used a swine model to test the hypothesis that LBW offspring would exhibit cerebrovascular dysfunction at later stages of life. Offspring from 14 sows were identified as normal birthweight (NBW) or LBW and were assessed at 28 (similar to end of infancy) and 56 (similar to childhood) days of age. LBW swine had lower absolute brain mass, but demonstrated evidence of brain sparing (increased brain mass scaled to body mass) at 56 days of age. The cerebral pulsatility index, based on transcranial Doppler, was increased in LBW swine. Moreover, arterial myography of isolated cerebral arteries revealed impaired vasoreactivity to bradykinin and reduced contribution of nitric oxide (NO) to vasorelaxation in the LBW swine. Immunoblotting demonstrated a lower ratio of phosphorylated-to-total endothelial NO synthase in LBW offspring. This impairment in NO signaling was greater at 28 vs. 56 days of age. Vasomotor responses to sodium nitroprusside (NO-donor) were unaltered, while Leu31, Pro34 neuropeptide Y-induced vasoconstriction was enhanced in LBW swine. Increases in total Y1 receptor protein content in the LBW group were not significant. In summary, LBW offspring displayed signs of cerebrovascular dysfunction at 28 and 56 days of age, evidenced by altered cerebral hemodynamics (reflective of increased impedance) coupled with endothelial dysfunction and altered vasomotor control. Overall, the data reveal that normal variance in birthweight of full-term offspring can influence cerebrovascular function later in life.

Amino acid-based compound activates atypical PKC and leptin receptor pathways to improve glycemia and anxiety like behavior in diabetic mice

Differences in glucose uptake in peripheral and neural tissues account for the reduced efficacy of insulin in nervous tissues. Herein, we report the design of short peptides, referred as amino acid compounds (AAC) with and without a modified side chain moiety. At nanomolar concentrations, a candidate therapeutic molecule, AAC2, containing a 7-(diethylamino) coumarin-3-carboxamide side-chain improved glucose control in human peripheral adipocytes and the endothelial brain barrier cells by activation of insulin-insensitive glucose transporter 1 (GLUT1). AAC2 interacted specifically with the leptin receptor (LepR) and activated atypical protein kinase C zeta (PKCς) to increase glucose uptake. The effects induced by AAC2 were absent in leptin receptor-deficient predipocytes and in Leprdb mice. In contrast, AAC2 established glycemic control altering food intake in leptin-deficient Lepob mice. Therefore, AAC2 activated the LepR and acted in a cytokine-like manner distinct from leptin. In a monogenic Ins2Akita mouse model for the phenotypes associated with type 1 diabetes, AAC2 rescued systemic glucose uptake in these mice without an increase in insulin levels and adiposity, as seen in insulin-treated Ins2Akita mice. In contrast to insulin, AAC2 treatment increased brain mass and reduced anxiety-related behavior in Ins2Akita mice. Our data suggests that the unique mechanism of action for AAC2, activating LepR/PKCς/GLUT1 axis, offers an effective strategy to broaden glycemic control for the prevention of diabetic complications of the nervous system and, possibly, other insulin insensitive or resistant tissues.

Potential Adult Neurogenesis in the Telencephalon and Cerebellar Cortex of the Nile Crocodile Revealed with Doublecortin Immunohistochemistry.

The brain of the crocodile is known to gain in mass allometrically throughout life, and the addition of neurons (as well as non-neurons) appears to play a significant role in this increasing brain mass. We used immunohistochemistry in the brains of 12 Nile crocodiles ranging between 350 g and 86 kg in body mass and 1.99 g to 7.9 g in brain mass to identify the regions of the brain in which neurons immunopositive for doublecortin (DCX), a marker for potential adult neurogenesis, are found. Similar to other reptiles, potential newly born neurons, those immunopositive for DCX, were found throughout the telencephalon, the main and accessory olfactory bulbs and the olfactory tract, and in the cerebellar cortex; however, no DCX immunopositive neurons were observed in the diencephalon or brainstem. An apparent moderate decrease in the density of DCX labeled neurons in the olfactory bulbs and tract as well as the cerebellar cortex was observed with increasing brain mass, but the observed qualitative density of labeled neurons within the telencephalon was maintained irrespective of brain mass. Three potential neurogenic zones, within the sulci of the lateral ventricle, were identified, and these are similar to those seen in other reptiles. This study indicates that at least part of the gain in brain mass with age in the Nile crocodile may be accounted for by the potential addition and integration of new neurons into the existing circuitry, especially so for the olfactory system, telencephalon and cerebellar cortex. Anat Rec, 301:659-672, 2018. © 2017 Wiley Periodicals, Inc.

It's getting bigger all the time: Estimating the Flynn effect from secular brain mass increases in Britain and Germany

Secular increases in brain mass over nearly a century have been noted for both males and females in the UK and Germany. It has been argued that such trends may be associated with the Flynn effect. The IQ gain predicted on the basis of these trends is 0.19 and 0.08 points per decade for UK, and 0.2 and 0.15 points per decade for German males and females respectively, indicating a small contribution to the Fullscale IQ trends in these countries (2.95% of the German decadal gain and 12.73% of the UK gain). There is also a sex difference in the rates of brain mass gain in both countries, favoring males. Temporal correlations between the secular trend in UK brain mass and European Flynn effects on Fullscale IQ, Crystallized, Fluid and Spatial abilities reveal correlations ranging from 0.751 in the case of Fluid ability to 0.761 in the case of Crystallized ability. The brain mass increase may be an imperfect proxy for changes in specific neuroanatomical structures important for IQ gains. Its small contribution to these gains is also consistent with the influence of other contributing factors. Increasing brain mass is predicted by the life history model of the Flynn effect as it suggests increased somatic effort allocation into bioenergetically expensive cortical real estate facilitating the development of specialized cognitive abilities.

When larger brains do not have more neurons: increased numbers of cells are compensated by decreased average cell size across mouse individuals.

There is a strong trend toward increased brain size in mammalian evolution, with larger brains composed of more and larger neurons than smaller brains across species within each mammalian order. Does the evolution of increased numbers of brain neurons, and thus larger brain size, occur simply through the selection of individuals with more and larger neurons, and thus larger brains, within a population? That is, do individuals with larger brains also have more, and larger, neurons than individuals with smaller brains, such that allometric relationships across species are simply an extension of intraspecific scaling? Here we show that this is not the case across adult male mice of a similar age. Rather, increased numbers of neurons across individuals are accompanied by increased numbers of other cells and smaller average cell size of both types, in a trade-off that explains how increased brain mass does not necessarily ensue. Fundamental regulatory mechanisms thus must exist that tie numbers of neurons to numbers of other cells and to average cell size within individual brains. Finally, our results indicate that changes in brain size in evolution are not an extension of individual variation in numbers of neurons, but rather occur through step changes that must simultaneously increase numbers of neurons and cause cell size to increase, rather than decrease.

Distinct physiological strategies are used to cope with constant hypoxia and intermittent hypoxia in killifish (Fundulus heteroclitus).

Many fish encounter hypoxia on a daily cycle, but the physiological effects of intermittent hypoxia are poorly understood. We investigated whether acclimation to constant (sustained) hypoxia or to intermittent diel cycles of nocturnal hypoxia (12 h normoxia:12 h hypoxia) had distinct effects on hypoxia tolerance or on several determinants of O2 transport and O2 utilization in estuarine killifish. Adult killifish were acclimated to normoxia, constant hypoxia, or intermittent hypoxia for 7 or 28 days in brackish water (4 ppt). Acclimation to both hypoxia patterns led to comparable reductions in critical O2 tension and resting O2 consumption rate, but only constant hypoxia reduced the O2 tension at loss of equilibrium. Constant (but not intermittent) hypoxia decreased filament length and the proportion of seawater-type mitochondrion-rich cells in the gills (which may reduce ion loss and the associated costs of active ion uptake), increased blood haemoglobin content, and reduced the abundance of oxidative fibres in the swimming muscle. In contrast, only intermittent hypoxia augmented the oxidative and gluconeogenic enzyme activities in the liver and increased the capillarity of glycolytic muscle, each of which should facilitate recovery between hypoxia bouts. Neither exposure pattern affected muscle myoglobin content or the activities of metabolic enzymes in the brain or heart, but intermittent hypoxia increased brain mass. We conclude that the pattern of hypoxia exposure has an important influence on the mechanisms of acclimation, and that the optimal strategies used to cope with intermittent hypoxia may be distinct from those for coping with constant hypoxia.

Expensive Brains: "Brainy" Rodents have Higher Metabolic Rate.

Brains are the centers of the nervous system of animals, controlling the organ systems of the body and coordinating responses to changes in the ecological and social environment. The evolution of traits that correlate with cognitive ability, such as relative brain size is thus of broad interest. Brain mass relative to body mass (BM) varies among mammals, and diverse factors have been proposed to explain this variation. A recent study provided evidence that energetics play an important role in brain evolution (Isler and van Schaik, 2006). Using composite phylogenies and data drawn from multiple sources, these authors showed that basal metabolic rate (BMR) correlates with brain mass across mammals. However, no such relationship was found within rodents. Here we re-examined the relationship between BMR and brain mass within Rodentia using a novel species-level phylogeny. Our results are sensitive to parameter evaluation; in particular how species mass is estimated. We detect no pattern when applying an approach used by previous studies, where each species BM is represented by two different numbers, one being the individual that happened to be used for BMR estimates of that species. However, this approach may compromise the analysis. When using a single value of BM for each species, whether representing a single individual, or available species mean, our findings provide evidence that brain mass (independent of BM) and BMR are correlated. These findings are thus consistent with the hypothesis that large brains evolve when the payoff for increased brain mass is greater than the energetic cost they incur.

CNS-directed AAV2-mediated gene therapy ameliorates functional deficits in a murine model of infantile neuronal ceroid lipofuscinosis

The neuronal ceroid lipofuscinoses (Batten disease) are a group of inherited neurodegenerative diseases characterized by the progressive intralysosomal accumulation of autofluorescent material in many cells, visual defects, seizures, cognitive deficits, and premature death. Infantile neuronal ceroid lipofuscinosis (INCL) has the earliest onset (≈1.5 years of age) and is caused by a deficiency in the lysosomal enzyme palmitoyl protein thioesterase-1 (PPT1). Currently there is no effective treatment for children with INCL. In this study, newborn PPT1-deficient mice received two (cortex), four (cortex and hippocampus), or six (cortex, hippocampus, and cerebellum) bilateral intracranial injections of AAV2-PPT1. The AAV-treated animals had localized increases in PPT1 activity, decreased autofluorescent material, improved histologic parameters, and increased brain mass. In addition, the treated animals had dose-dependent improvements in a battery of behavioral tests and improved interictal electroencephalographic tracings. However, there was neither a significant decrease in seizure frequency nor an increase in longevity even in INCL animals receiving six injections. These data suggest that early treatment of INCL using gene transfer techniques can be efficacious. However, higher levels or a broader distribution of PPT1 expression, or both, will be required for more complete correction of this neurodegenerative disease.

Neuron numbers in sensory cortices of five delphinids compared to a physeterid, the pygmy sperm whale

With its large mass and enormous gyrification, the neocortex of whales and dolphins has always been a challenge to neurobiologists. Here we analyse the relationship between neuron number per cortical unit in three different sensory areas and brain mass in six different toothed whale species, five delphinids and one physeterid. Cortex samples, including primary cortical areas of the auditory, visual, and somatosensory systems were taken from both hemispheres of brains fixed in 10% buffered formalin. The samples were embedded in paraffin, sectioned at 25 μm thickness and stained with cresyl violet. Because cortical thickness varies among toothed whale species, cell counts were done in cortical units measuring 150 μm in width, 25 μm in thickness, and extending from the pial surface to the white matter. By arranging the delphinid brains according to their total mass, 834–6052 g, we found decreasing neuron numbers in the investigated areas with increasing brain mass. The pigmy sperm whale ( Kogia breviceps), a physeterid with an adult brain weight of 1000 g had a distinctly lower neuron number per cortical unit. As had been expected, an increase in adult brain weight in delphinid cetaceans (family Delphinidae) is not correlated with an increase in neuron number per cortical unit.

A method of obtaining animals with increased brain mass

A method of obtaining animals with increased brain mass

BRAIN SIZE, ADAPTATION AND HETEROCHRONY IN GEOMYOID RODENTS.

Of the many unusual morphological features that characterize mammals, perhaps the most intriguing and least understood is the enlarged brain. Among mammals, brain weight and body weight are allometrically related and follow the equation brain weight = k(body weight)a, where k is the allometric coefficient and a is the allometric exponent. The allometric exponent (regression coefficient) on a double logarithmic plot of brain weight on body weight across the Mammalia is estimated to be .74 (Eisenberg and Wilson, 1978; Martin, 1981; Armstrong, 1983); that is, larger mammals tend to have proportionately smaller brains. However, within groups of mammals, certain lineages show unusually enlarged brains; in such cases, brain mass far exceeds that predicted based on body mass alone. Examples of highly encephalized species are found in disparate mammalian lineages and at different taxonomic levels: pteropodid bats and humans exhibit greater encephalization than do other families in their respective orders (Jerison, 1973; Eisenberg and Wilson, 1978); certain porpoises and dolphins (Delphinidae), including Tursiops, Grampus, and Orcinus, stand out as the most encephalized cetaceans (Jerison, 1973, 1981; Osborne and Sundsten, 1981); opossums of the genus Caluromys seem to have larger brains in proportion to body size than do other didelphid marsupials (Eisenberg and Wilson, 1981); and relative brain size in certain species of white-footed mice (e.g., Peromyscus crinitus, P. truei, and P. pectoralis) exceeds that seen in other species of the genus (Mace and Eisenberg, 1982). Hypotheses designed to account for these unusually encephalized species of mammals are of two basic types. The first, which we term specialization, is founded on the assumption that increased specialization of a function (motor, sensory, or cognitive) requires increased brain mass to control that function (the principle of proper mass; Jerison, 1973). According to this view, relative brain size is a reliable index of both a species' trophic behavior and the complexity of the species' habitat (Findley and Wilson, 1982). This hypothesis directs one to search for ecoethological specializations in largebrained species to better understand the evolution of encephalization (for examples see Mann, 1963; Stephan and Pirlot, 1970; Pirlot and Pottier, 1977; Eisenberg and Wilson, 1978, 1981; Clutton-Brock and Harvey, 1980; Lemen, 1980; Mace et al., 1981; Roth and Thorington, 1982; Meier, 1983). The second hypothesis, articulated most recently by Gould (1977), suggests that the unusually enlarged brain may have originated through time shifts in an ancestral developmental sequence (heterochrony) resulting in a paedomorphic descendant possessing the proportionately large brain characteristic of the juvenile ancestor. According to the heterochrony hypothesis, then, one might search for evidence of ontogenetic perturbations in large-brained species to better understand the evolution of brain size. It is important to observe that these ideas are not directly competitive. The eco-ethological specialization hypothesis focuses on present use of the enlarged brain (with extrapolations as to its ori-