Sonia Sequeira

Cyborg: ‘cybernetic + organism’?!!

Well, no, not yet. However, the successful development of a noninvasive neuroelectronic interface system consisting of an elementary circuit of two neurons synaptically connected to a semiconductor chip presages the advent of an era of neurocomputation and neuroengineering. The study by Zeck and Fromherz at the Max-Planck Institute in Munich shows that individual neurons from the snail Lymnaea stagnalis, immobilized onto a microelectronic substrate establish a signaling circuit connected by strong electric synapses propagating action potentials, which can be measured and controlled electronically. With further technological refining, the neuroelectronic model described in this study will probably simplify the study of synaptic modulation in neuronal networks and help unravel the underlying mechanisms of memory. Proc. Natl. Acad. Sci. U. S. A. 98, 10457–10462. SS

α-Synuclein degradation by parkin is impaired in Parkinson's disease

Parkin is an E3 ubiquitin ligase, which attaches a signaling tag called ubiquitin to proteins destined to be destroyed in proteosomes, in an overall process known as ubiquitination. Previous findings have shown that α-synuclein, a small phosphoprotein involved in synaptic vesicle transport, colocalizes with ubiquitin in Lewy bodies that are found in brain tissue from Parkinsons disease (PD) patients, and mutations in both parkin and α-synuclein have been linked to PD. In a recent edition of Science [(2001) 293, p.224], Shimura et al. have shown that (1) α-synuclein and parkin interact in vivo and (2) that point mutations in parkin that are typical of the autosomal-recessive juvenile form of PD (AR-JP), impair the degradation of α-synuclein by ubiquitination, leading to the accumulation of toxic, non-ubiquitinated α-synuclein in brain. Although several important questions remain – such as whether other neurotoxic parkin substrates are incorrectly ubiquinated and destroyed in PD, and whether the accumulation of these substrates in brain is directly associated with dopaminergic cell loss in AR-JP patients – given that α-synuclein accumulates in large amounts within Lewy bodies, it is highly likely to have a major role in dopaminergic cell death. SS

A complex role for genetics in autism

Laboratory rodents housed in standard, empty cages exhibit stereotypic behaviors that could indicate brain abnormalities, reported Joseph Garner of the University of California, Davis, at the International Society for Applied Ethology Congress. The stereotypies – pacing, incessant grooming, repetitive cage biting and scratching – are most prevalent in these nocturnal animals at night, and are often underappreciated by researchers who work with animals during the day. As stereotypies in humans are associated with basal ganglia damage, and mice raised in enriched environments have been shown to have more neurons and better memory, these findings have implications for many studies in the neurosciences. LO

Randomness and creativity

In an exquisitely orchestrated system such as the brain, an integrated ‘randomizing’ mechanism could play a crucial role in eliciting novel ideas and actions. To date, unexplained variability in brain responses has been attributed to noise in incoming stimuli, but at the Annual Meeting of the British Association for the Advancement of Science Roger Carpenter of the University of Cambridge and his team reported that groups of brain cells respond differently, and are independently and randomly integrated into the brains response to stimuli. The study indicates that the time taken by brain cells to register a flash of light varies widely from one flash to the next as a result of independent processing of clusters of cells. If one considers that the brain processes several stimuli simultaneously, changes in the response time will eventually lead to different actions. The result of this process could be creativity itself, the randomness providing a source of new variations of behavior and ideas, desirable in several human activities. SS

A case of neuroferritinopathy

A new human disease akin to Huntingtons disease and parkinsonism has been identified that is caused by the abnormal formation of ferritin aggregates in the basal ganglia of the brain. Curtis et al. (Nat. Genet. 28, 350–353) have now reported a mutation in the ferritin l-chain (19q13.3) that causes a dominant adult-onset neuropathology which they have coined as neuroferritinopathy. Symptoms of extrapyramidal dysfunction such as dystonia, spacticity and rigidity characterized this novel disease. In brain, ferritin (FT) functions as an intracellular store and detoxification site for iron. It is likely, the authors suggest, that the mutant l-chain discovered could increase its susceptibility to proteolysis and that the consequent release of highly toxic iron from putative storage proteins might induce oxidative stress and neuronal cell death. SS

New Parkinson's website

New Parkinson’s website The Parkinson’s disease research effort has been advanced by the launching of a new Parkinson’s Disease Research Website (http://www.ninds.nih.gov/ parkinsonsweb). The site highlights ongoing progress on the NIH’s five-year Parkinson’s Agenda, and is the first website of its kind at NIH. It is designed to provide information on scientific advances, funding opportunities, clinical trials, centers and more. Private organizations and government agencies other than NIH will also have an opportunity to showcase their parallel efforts on Parkinson’s disease research. As the exchange of information accelerates with the Parkinson’s web, so potentially could research towards a safe and effective treatment. (Diane D. Murphy and Carlos Pena, NINDS/NIH)

News & CommentIn Brief

Spinal cord injury (SCI) occurs with an annual frequency of ~4 in 100 000 people in the USA. In the adult CNS there is little capacity for axonal regeneration, and the extent of recovery decreases as age at the time of SCI increases. One approach to the problem of SCI is to transplant fetal spinal cord tissue into the site of a spinal cord lesion. If this technique is combined with application of neurotrophins (molecules that promote neuronal growth) axonal regeneration within the host spinal cord is enhanced. Coumans et al. [1] have discovered that axonal regeneration and functional recovery in the adult rat are further enhanced if fetal spinal cord tissue and neurotrophins are applied two to four weeks following injury. The authors completely transected the spinal cord at the T6–T7 level in adult Sprague Dawley rats. Some animals had embryonic day 14 (E14) fetal spinal cord tissue transplanted across the transected spinal cord, either immediately or two to four weeks following transection. Subcutaneous osmotic minipumps delivered either saline, brain derived neurotrophic factor (BDNF, 2 mg ml–1) or neurotrophin-3 (NT-3, 1 mg ml–1), at a rate of 0.5 μl hr–1, continuously for 14 days. In transplanted animals, host axons grew sparsely into the transplant, and the presence of neurotrophins increased axonal regrowth. Surprisingly, the percentage of animals showing axonal regrowth, and the density, length and branching of fibres, were all highest if the transplant and neurotrophins were given two weeks after transection. The functional consequences of delayed transplants were remarkable. In nontransplanted animals, and those that received transplants but not neurotrophins, voluntary hind limb movement was abolished. However, 20% of animals that received transplants and neurotrophins two weeks after transection showed weight-supported stepping ability. Animals transplanted four weeks after transection also showed hind limb motor recovery, indicating that neurons retain their regenerative potential even this long after the original damage. Animals that received immediate transplants and neurotrophins did not show such recovery. Thus, the investigators showed that the treatment of SCI using fetal tissue implants and neurotrophins was more effective if it was delayed. This study shows that the window for medical intervention in SCI incidents might be longer than previously thought, and also opens up a new school of thought in which delaying a potential treatment of SCI could significantly enhance prospects of functional recovery.

The power of belief

l-Dopa and apomorphine are active drugs used in the treatment of patients suffering from Parkinsons disease (PD), a neurodegenerative disease in which the dopaminergic pathway involved in the regulation of behavioral and sensorimotor functions is severely impaired. The mechanisms involved are still poorly understood; however, a recent study has demonstrated that the level of expectation of benefit from treatment might influence and enhance the endogenous release of dopamine from the nigralstriatal pathway independently of the efficacy of the drug. In order to evaluate the power of the placebo effect in PD, researchers have studied the binding of the competitive dopamine receptor ligand [11C] raclopride by PET scanning. Patients receiving placebo or active drug showed comparably less binding of RAC in the striatum, indicating endogenous release of dopamine. The results published in Science (293, 1164–1166) highlight the importance of placebo controls in evaluating therapeutical intervention. SS

Chill-out with neuropeptide Y

Transgenic rats overexpressing hippocampal neuropeptide Y (NPY) were generated to study the role of endogenous NPY in controlling anxiety. Transgenic rats were specifically insensitive to normal anxious behavior induced by restraint and punishment tests and showed impaired spatial memory. The data confirms previous pharmacological studies suggesting an anti-stress function for NPY and is the first study that correlates NPY with learning and memory. Proc. Natl. Acad. Sci. U. S. A. (2000) 97, 12852–12857. (SS)

Tracking down the origins of HIV

Researchers have proposed a new theory for the spread of HIV to humans based on the discovery of a 17th-century predecessor of the virus, common to humans and chimpanzees. Using genetic database analysis, the group has found that the most common form of AIDS, HIV-1 M, must have spread to humans long before the 1950s, during which the polio vaccination programs in Africa were thought to have contaminated African populations with the precursor virus found in chimps. The data suggests that transmission to man took place as a result of hunting chimpanzees for meat, and spread outwards from Africa with mass migration, decolonization and war. FASEB J. (2000) Ahead of print report. (SS)