The social brain?

The notion that there is a 'social brain' in humans specialized for social interactions has received considerable support from brain imaging and, to a lesser extent, from lesion studies. Specific roles for the various components of the social brain are beginning to emerge. For example, the amygdala attaches emotional value to faces, enabling us to recognize expressions such as fear and trustworthiness, while the posterior superior temporal sulcus predicts the end point of the complex trajectories created when agents act upon the world. It has proved more difficult to assign a role to medial prefrontal cortex, which is consistently activated when people think about mental states. I suggest that this region may have a special role in the second-order representations needed for communicative acts when we have to represent someone else's representation of our own mental state. These cognitive processes are not specifically social, since they can be applied in other domains. However, these cognitive processes have been driven to ever higher levels of sophistication by the complexities of social interaction.     

Lipoxygenation in rat brain?

It has been previously claimed that rodent brain possesses lipoxygenase activity, based upon the structure of products which were formed from arachidonic acid and the inhibition of this activity by "lipoxygenase inhibitors." Our studies confirm that various positional isomers of hydroxyeicosatetraenoic acids (HETE) are formed (e.g., 15-, 12-, 11-, 9-, 8- and 5-HETE) by brain homogenate and that their production is inhibited by certain lipoxygenase inhibitors, such as nordihydroguaiaretic acid (NDGA) but not by cyclooxygenase or cytochrome P-450 inhibitors. However, stereochemical analysis indicated racemic distributions of these products suggesting that they were not formed by a lipoxygenase enzyme but rather by a peroxidative process. It should also be noted that the presence of 12(S)-lipoxygenase activity could be demonstrated by stereochemical analysis only when the brain was not perfused properly, indicating this activity was due to blood cell contamination. It is known that many lipoxygenase inhibitors are also capable of inhibiting peroxidative reactions apparently due to their free radical scavenging properties. For these reasons, it is essential that the stereochemical purity of purported lipoxygenase products be determined and that previous claims of lipoxygenase activity in mammalian brain be reexamined.     

Cognitive-motor brain–machine interfaces

Brain–machine interfaces (BMIs) open new horizons for the treatment of paralyzed persons, giving hope for the artificial restoration of lost physiological functions. Whereas BMI development has mainly focused on motor rehabilitation, recent studies have suggested that higher cognitive functions can also be deciphered from brain activity, bypassing low level planning and execution functions, and replacing them by computer-controlled effectors. This review describes the new generation of cognitive-motor BMIs, focusing on three BMI types:

• 1.Speech BMI – reconstructing a person’s speech based on the neuronal activity.
• 2.Direct object control – controlling object movement without mimicking the limb movement that would yield the desired object movement.
• 3.Decoding internal processes, such as neuronal representations of sensory information and decision making.

By outlining recent progress in developing these BMI types, we aim to provide a unified view of contemporary research towards the replacement of behavioral outputs of cognitive processes by direct interaction with the brain.     

Chemo brain: From discerning mechanisms to lifting the brain fog—An aging connection

Mounting evidence indicates that cancer treatments cause numerous deleterious effects, including central nervous system (CNS) toxicity. Chemotherapy-caused CNS side effects encompass changes in cognitive function, memory, and attention, to name a few. Although chemotherapy treatment-induced side effects occur in 16–75% of all patients, the mechanisms of these effects are not well understood. We have recently proposed a new epigenetic theory of chemo brain and, in a pioneer study, determined that cytotoxic chemotherapy agents induce oxidative DNA damage and affect molecular and epigenetic processes in the brain, and may be associated with brain aging processes.

In this paper, we discuss the implications of chemo brain epigenetic effects and future perspectives, as well as outline potential links with brain aging and future translational research opportunities.     

Which brain defects accompany cyclopia?

We report a fetus with an association of cyclopia without proboscis, aprosencephaly and agnathia. Analysing literature cases and the case presented here we can suggest that: 1) not only alobar holoprosencephaly but also more severe forebrain anomalies can be a brain equivalent of cyclopia; 2) aprosencephaly can be viewed as the earliest known variant of prosencephalic series; and 3) "agnathia-holoprosencephaly" association is etiologically heterogeneous.     

Statins--a cure-all for the brain?

'Statins' are 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors - oral cholesterol-lowering drugs that are used to treat hypercholesterolaemia. It is widely accepted that statins have anti-inflammatory effects that are independent of their ability to lower cholesterol. Animal studies and observational clinical studies have indicated that statins might also be effective in treating certain neurological diseases - in particular, multiple sclerosis, Alzheimer's disease and ischaemic stroke. At present, however, results from ongoing prospective, randomized clinical trials are not available.     

Aβ(42) induced MRI changes in aged rabbit brain resembles AD brain

Alzheimer’s disease is the most common form of dementia and is structurally characterized by brain atrophy and loss of brain volume. Aβ is one of the widely accepted causative factors of AD. Aβ deposition is positively correlated with brain atrophy in AD. In the present study, structural brain imaging techniques such as Magnetic Resonance Imaging (MRI) were used to measure neuroanatomical alterations in Alzheimer’s disease brain. MRI is a non-invasive method to study brain structure. The objective of the present study was to elucidate the role of Aβ on brain structure in the aged rabbit brain. Among 20 aged rabbits, one batch (n = 10) rabbits was injected chronically with Aβ(1-42) and another batch (n = 10) with saline. The MRI was conducted before Aβ(1-42)/saline injection and after 45 days of Aβ(1-42)/saline injection. All the aged rabbits underwent MRI analysis and were euthanized after 45 days. The MRI results showed a significant reduction in thickness of frontal lobe, hippocampus, midbrain, temporal lobe and increases in the lateral ventricle volume. We also conducted an MRI study on AD (n = 10) and normal (n = 10) cases and analyzed for the thicknesses of frontal lobe, hippocampus, midbrain, temporal lobe and lateral ventricle lobe. We found significant reductions in thickness of the frontal lobe and the hippocampus. However, no significant reduction in the thickness of midbrain, temporal lobe or increase in the lateral ventricle volume was observed compared to normal. Correlations in brain atrophy changes between rabbit brain and human AD brain were found for frontal lobe and hippocampal regions. In contrast, other regions such as midbrain, temporal lobe, and lateral ventricles were not correlated with rabbit brain atrophy changes in the corresponding regions. The relevance of these changes in AD is discussed.     

Blood–brain barrier peptide shuttles

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What brain signals are suitable for feedback controzl of deep brain stimulation in Parkinson's disease?

Feedback control of deep brain stimulation (DBS) in Parkinson's disease has great potential to improve efficacy, reduce side effects, and decrease the cost of treatment. In this, the timing and intensity of stimulation are titrated according to biomarkers that capture current clinical state. Stimulation may be at standard high frequency or intelligently patterned to directly modify specific pathological rhythms. The search for and validation of appropriate feedback signals are therefore crucial. Signals recorded from the DBS electrode currently appear to be the most promising source of feedback. In particular, beta-frequency band oscillations in the local field potential recorded at the stimulation target may capture variation in bradykinesia and rigidity across patients, but this remains to be confirmed within patients. Biomarkers that reliably reflect other impairments, such as tremor, also need to be established. Finally, whether brain signals are causally important needs to be established before stimulation can be specifically patterned rather than delivered at empirically defined high frequency.     

An immunohistochemical analysis of SERT in the blood–brain barrier of the male rat brain

5-Hydroxytryptamine (5-HT) was originally discovered as a vasoconstrictor. 5-HT lowers blood pressure when administered peripherally to both normotensive and hypertensive male rats. Because the serotonin transporter (SERT) can function bidirectionally, we must consider whether 5-HT can be transported from the bloodstream to the central nervous system (CNS) in facilitating the fall in blood pressure. The blood–brain barrier (BBB) is a highly selective barrier that restricts movement of substances from the bloodstream to the CNS and vice versa, but the rat BBB has not been investigated in terms of SERT expression. This requires us to determine whether the BBB of the rat, the species in which we first observed a fall in blood pressure to infused 5-HT, expresses SERT. We hypothesized that SERT is present in the BBB of the male rat. To test this hypothesis, over 500 blood vessels were sampled from coronal slices of six male rat brains. Immunofluorescence of these coronal slices was used to determine whether SERT and RecA-1 (an endothelial cell marker) colocalized to the BBB. Blood vessels were considered to be capillaries if they were between 1.5 and 23 µm (intraluminal diameter). SERT was identified in the largest pial vessels of the BBB (mean ± SEM = 228.70 ± 18.71 µm, N = 9) and the smallest capillaries (mean ± SEM = 2.75 ± 0.12 µm, N = 369). SERT was not identified in the endothelium of blood vessels ranging from 20 to 135 µm (N = 45). The expression of SERT in the rat BBB means that 5-HT entry into the CNS must be considered a potential mechanism when investigating 5-HT-induced fall in blood pressure.     

Recording brain waves at the supermarket: what can we learn from a shopper's brain?

Communication and marketing campaigns have traditionally been divided into two lines: above the line (ATL) and below the line (BTL). ATL campaigns refer to communications such as TV, print, and outdoor displays that are intended to reach large audiences. The effects of ATL are inherently difficult to measure; we do not see the direct consequences of viewing an advertisement (i.e., a talking baby giving financial advice) and actual purchase of the product. ATL is intended to indirectly improve the impression of a brand. BTL campaigns refer to promotions and in-store displays and are designed to affect the point-of-purchase behavior. The effects of BTL are easier to measure; we see direct consequences of viewing a display (i.e., “Today Only, Two for the Price of One”) and eventual purchase of the product. BTL is intended to directly improve the impression of a brand. Neuroscience plays an important role in measuring the effects of marketing campaigns. Traditional methods of measurement (such as surveys and interviews) depend on the verbal ability of the consumer to articulate their motivations for purchasing a product. It is well known that participants are poor at introspective reasoning, leading to an eventual purchase that omits emotional elements. Recently, methods normally employed in cognitive neuroscience have been adapted for use in the evaluation of campaign effectiveness. These methods have increased our understanding of factors leading to economic decisions. The application of neuroscience in ATL campaigns is relatively straightforward. Participants view TV commercials, for example, seated in a comfortable setting with minimal movement while electroencephalogram (EEG) measures are monitored. These brain waves reveal cognitive events related to the media. Participants are exposed to a functional magnetic resonance imaging (fMRI) scanner to monitor changes in blood flow in various regions of the brain. Both of these methods are sensitive to underlying cognitive and emotional activity and are complimentary. EEG is more sensitive to time-locked events (i.e., story lines), whereas fMRI is more sensitive to the brain regions involved. The application of neuroscience in BTL campaigns is significantly more difficult to achieve. Participants move unconstrained in a shopping environment while EEG and eye movements are monitored. In this scenario, fMRI is not possible. fMRI can be used with virtual store mock-ups, but it is expensive and seldom used. We have developed a technology that allows for the measurement of EEG in an unobtrusive manner. The intent is to record the brain waves of participants during their day-to-day shopping experience. A miniaturized video recorder, EEG amplifiers, and eye-tracking systems are used. Digital signal processing is employed to remove the substantial artifact generated by eye movements and motion. Eye fixations identify specific viewings of products and displays, and they are used for synchronizing the behavior with EEG response. The location of EEG sources is determined by the use of a source reconstruction software.     

Alpha synuclein is transported into and out of the brain by the blood–brain barrier

Alpha-synuclein (α-Syn), a small protein with multiple physiological and pathological functions, is one of the dominant proteins found in Lewy Bodies, a pathological hallmark of Lewy body disorders, including Parkinson's disease (PD). More recently, α-Syn has been found in body fluids, including blood and cerebrospinal fluid, and is likely produced by both peripheral tissues and the central nervous system. Exchange of α-Syn between the brain and peripheral tissues could have important pathophysiologic and therapeutic implications. However, little is known about the ability of α-Syn to cross the blood–brain barrier (BBB). Here, we found that radioactively labeled α-Syn crossed the BBB in both the brain-to-blood and the blood-to-brain directions at rates consistent with saturable mechanisms. Low-density lipoprotein receptor-related protein-1 (LRP-1), but not p-glycoprotein, may be involved in α-Syn efflux and lipopolysaccharide (LPS)-induced inflammation could increase α-Syn uptake by the brain by disrupting the BBB.     

Distribution of acetylated α-tubulin in brain

Summary We studied the solubility properties of brain acetylated -tubulin, as well as the localization of this tubulin in brain tissue. Endogenous unpolymerized tubulin and cytoskeletal tubulin were fractionated after brain Triton-solubilization. Using the immunoblotting technique, we found that acetylated -tubulin was recovered in the cytoskeletal fraction, and that most (92%) of the acetylated microtubules of this fraction were depolymerized by cold/Ca²⁺ treatment. In another set of experiments, axonal and soma-dendritic preparations were found to have equivalent amounts of acetylated -tubulin. By immunogold electron microscopy, we established that acetylated microtubules are widely distributed in dendrites of the central nervous system.     

A new blood–brain barrier model using primary rat brain endothelial cells,pericytes and astrocytes

Blood–brain barrier (BBB) characteristics are induced and maintained by cross-talk between brain microvessel endothelial cells and neighbouring elements of the neurovascular unit. While pericytes are the cells situated closest to brain endothelial cells morphologically and share a common basement membrane, they have not been used in co-culture BBB models for testing drug permeability. We have developed and characterized a new syngeneic BBB model using primary cultures of the three main cell types of cerebral microvessels. The co-culture of endothelial cells, pericytes and astrocytes mimick the anatomical situation in vivo. In the presence of both pericytes and astrocytes rat brain endothelial cells expressed enhanced levels of tight junction (TJ) proteins occludin, claudin-5 and ZO-1 with a typical localization at the cell borders. Further morphological evidence of the presence of interendothelial TJs was provided by electron microscopy. The transendothelial electrical resistance (TEER) of brain endothelial monolayers in triple co-culture, indicating the tightness of TJs reached 400 Ω cm² on average, while the endothelial permeability coefficients (P_e) for fluorescein was in the range of 3 × 10^?6 cm/s. Brain endothelial cells in the new model expressed glucose transporter-1, efflux transporters P-glycoprotein and multidrug resistance protein-1, and showed a polarized transport of rhodamine 123, a ligand for P-glycoprotein. To further characterize the model, drug permeability assays were performed using a set of 19 compounds with known in vivo BBB permeability. Good correlation (R² = 0.89) was found between in vitro P_e values obtained from measurements on the BBB model and in vivo BBB permeability data. The new BBB model, which is the first model to incorporate pericytes in a triple co-culture setting, can be a useful tool for research on BBB physiology and pathology and to test candidate compounds for centrally acting drugs.