However, it really isn’t a reasonable possibility. If there was an Intelligent Designer, then sure, why would baby neurons pop up and then not turn into functioning adult neurons? But if there is no Intelligent Designer, and instead, things evolved, then it is quite possible that the lack of novel fully formed and hooked up neurons in an adult human (which seems to be the general rule of thumb, for whatever reason) is not necessarily achieved via some highly sensible planned out feature. Rather, it is most likely that an evolved feature is a kludge. If it turns out that neurogenesis occurs in the adult human nose but that those nascent neurons never enervate, well, that is what we might expect evolution, which is not intelligent but, rather, pragmatic, to come up with.

The method of testing this idea, applied by Jonas Frisén of the Karolinska Institute in Stockholm, is just as interesting as the finding itself. The idea is to date the neurons in the nose. One way to date organic tissue might be to use C-14 dating like archaeologists use, but that method is not precise enough. The neural tissue in a living human might be something like “50 years old plus or minus 80 years” which would not be too useful. But there is a way to use C-14 after all. Since atomic testing started, there has been a LOT more C-14 pushed into the atmosphere, and the added radiocarbon allows for a more precise atomic clock, if the clock is properly calibrated. This method was initially pioneered a few years ago in the forensic case of two sisters who were found dead, long after they had expired, in their home in Vienna. Both sisters had considerable wealth, and the one who died first would have passed on that wealth to the second, living sister. The relatives of the second-to-die sister would therefore receive a considerably larger inheritance than the relatives of the first-to-die sister. The two sisters’ bodies were found semi-mummified, and a couple of years after death, in their apartment which was surrounded by neighbors who never noticed they were no longer around.

The post-A-bomb calibrated C-14 method was used to determine that the sisters had in fact died about a year apart. This method has subsequently been used for other fine-tuned post atomic dating. (There is a write-up of this here.)

OK, now back to the nose.

In the new study, published this week in Neuron, Frisén, Spalding, and colleagues measured levels of ¹⁴C in olfactory bulb tissue taken during autopsy from the brains of 15 subjects who were born either before or after the atomic testing period. The researchers found that the neurons in the olfactory bulb were all the same age: the age of the individual they came from. “[That’s] evidence that in humans, in this area, neurogenesis doesn’t occur,” says Frisén.

There is still evidence, i.e. from mice, that neurogenesis of useful neurons does happen in some mammals. The question of novel nose neurons is not entirely settled. But, when the question comes up “Do humans generate new neurons as adults” please make sure that the assumption that they do is not based on this earlier nose research, or on any studies that merely looked for new neuron proteins.

In addition, Macklis points out that the tissue samples may have biased the results. The donors in the study died at the Karolinska Institute, he notes, and some had a history of substance abuse or psychiatric illness, both of which have been shown to decrease neurogenesis. He says that a better test would be to repeat the experiment in healthy people constantly exposed to new scents—chefs, sommeliers, perfumers, or travelers to exotic locales.

Face it: there is still some head scratching going on. We will need to keep an eye on this nose research before sealing our lips on it, and in the mean time, keep your chin up.

Photo courtesy of flickr user Lawrence Whittemore

Hat Tip: Virginia Hughes. Who also has something interesting on Coffee.

• Multiple sclerosis (failure of remyelination)
• amyotrophic lateral sclerosis
• spinocerebellar ataxia
• Parkinson’s disease
• Huntington’s disease
• Neuropathic pain, which turns out to be a kind of “neuroimmune disorder”
• Cerebrovascular disease (inappropriate control of blood flow within the brain)
• Brain ischemia (a cerebrovascular disorder)

Dissecting demyelination by Miller and Mi (2007) covers the issue of Central Nervous System loss of myelin. Myelin is a phospholipid tissue that covers the axon of a neuron in roughly the same way that insulation covers a wire. It provides structural support and protection and keeps axons that are bundled up in a nerve apart from each other. Functionally, myelin makes the electrical component of neural signal propagation more efficient. Nerve impulses consist of chemical processes which build up electrical potential in a part of the neuron followed by the movement of that electric charge downstream along the neural tissue (generally along the elongated axon). The chemical part of this takes a lot of time, while the electrical part is quick. In the absence of myelin, the distance the electrical charge goes before it induces the chemical process downstream is short. In the presence of myelin, each of these saltations of electrical potential down the axon is lengthened considerably. Thus, the propagation of an electrical signal down an axon is much faster if the axon is covered by a myelin sheath, and the signal is less likely to propagate inappropriately across to an adjoining axon.The process of myelination is part of neural development in organisms with a Central Nervous System (and others). Until myelination occurs, neural circuits that are otherwise hooked up and ready to go may function incorrectly or not at all. One of the main reasons that a six month old human child can’t walk is because the circuits critical to coordinating muscle movement to allow this form of locomotion are not yet myelinated.Demyelination is the loss of this myelin sheath, and is the cause of several nasty diseases. From Miller and Mi:

The loss of central nervous system myelin and the failure of remyelination by oligodendrocytes contribute to the functional impairment that characterizes diseases such as multiple sclerosis. Why myelin repair fails in multiple sclerosis is currently unclear; … We propose that successful myelin repair of the adult CNS recapitulates a sequence of stages that generally correlate with those seen during development…

During neural development, cells that are not fully differentiated (a kind of latter-day stem cell) start to differentiate into two kinds of glial cells, astrocytes and oligodendrocytes. In humans (and mammals generally) this occurs late in embryonic development in response to molecular signals that re, in turn, localized into various zones. This is part of the process of going from an undifferentiated “neural tube” to a more differentiated central nervous system. It is a fairly complicated process with several stages of cell reproduction, migration, and differentiation.Miller and Mi explore the possibility that myelin repair follows a similar sequence of events, at least with respect to cell differentiation, and thus, diseases that have to do with failure of myelin repair … such as occurs in the disease multiple sclerosis … can be understood with this model. They attempt to identify the vulnerable steps in the myelination process as possible points at which failure occurs. They note that current treatment of diseases like MS involve trying to slow down the degeneration of myelin, and trying to interfere with the immune system activity that causes that degeneration. But if you see myelin formation and degeneration as a dynamic process, the former offsetting the latter, then additional approaches that enhance post-development formation (remyelination) would be the most effective treatment.They could be wrong. It is possible that the process of remyelination that occurs naturally is distinctly different from the initial developmental process that starts in the embryo and continues through early development of the organism. One reason to suspect that they are different, in my opinion, is that the kinds of developmental-regulatory genes that are busy during development may be inactive in the adult. Thus, the signalling proteins that would regulate the initial myelination may be replaced with some other form of signalling later. This, however, may not matter too much if the important and applicable parts of the model are not the signals but rather the stages of differentiation.Lobsiger and Cleveland, in “Glial cells as intrinsic components of non-cell-autonomous neurodegenerative disease” review advances in thinking about “neurotoxic” cause of diseases such as amyotrophic lateral sclerosis (ALS), spinocerebellar ataxia (SCA), Huntington’s disease, Parkinson’s disease and multiple system atrophy (MSA). In a nutshell: These disorders involve a genetically caused toxic effect that kills neural cells. New research, however, suggests that there is likely an interaction between the neural cells and various glial cells.

As most neurodegenerative disease-linked mutant proteins are widely expressed, it is likely that their expression outside the vulnerable neurons, especially within glial cells, contributes to disease mechanisms. Mutant products within glial cells drive toxicity to neighboring neurons either by release of toxic components or by mutant-mediated reduction in one or more neuronal support functions…

So just as glial cells serve to support and maintain neurons, they can also contribute to their degeneration. That makes sense and does not seem surprising, but the mechanism is complex and need to be understood at a fine level in order to develop treatments.Along similar lines, Scholz and Woolf (2007) discuss findings indicating that neuropathic pain arises in part from glial cells. Neuropathic pain is pain that does not originate from pain receptors (specialized neurons) but rather, from somewhere else along the pathway that normally leads form those pain sensing neurons to the brain. Like a “pinched nerve.” But again, as with toxic neural cell death, the details are complex, and the mechanism for neuropathic pain involves immune cells and glial cells as well as the neurons.

The contribution of immune cells and glia to the development and the persistence of pain after nerve injury challenges conventional concepts that are biased toward neurons being responsible for the pathophysiological changes that drive neuropathic pain. … Differentiating between the good, the bad and the ugly aspects of immune and glial responses to nerve injury will be essential for developing targeted new treatment strategies for neuropathic pain.

Does your body use more energy when you think really really hard about something? Could this be the latest, greatest diet fat? Well, yes and no. First of all, how hard you are thinking and how hard your cerebral neurons are working may be fairly unrelated because “thinking” is “conscious” and that is only a small part of what your brain is up to. Other parts of the brain are doing things such as figuring out how to make you believe that you have free will, or that you are not really driving down Main Street instead of the more obvious Springfield Boulevard because the donut shop is on Main Street and you might just stop there ….Anyway, Iadecola and Nedergaard (2007) explore the fascinating question of how the blood supply system for the brain manages to supply extra stuff (oxygen and glucose) where needed, in particular, where those neurons are extra busy. It turns out to involve, guess what, glial cells. In particular, “astrocytes, cells with extensive contacts with both synapses and cerebral blood vessels, participate in the increases in flow evoked by synaptic activity. Their organization in nonoverlapping spatial domains indicates that they are uniquely positioned to shape the spatial distribution of the vascular responses that are evoked by neural activity.” How cool is that?For the remaining two major contributions to this special issue, I’ll just supply the abstracts:Rossil et al (2007):

Astrocyte metabolism and signaling during brain ischemiaBrain ischemia results from cardiac arrest, stroke or head trauma. These conditions can cause severe brain damage and are a leading cause of death and long-term disability. Neurons are far more susceptible to ischemic damage than neighboring astrocytes, but astrocytes have diverse and important functions in many aspects of ischemic brain damage. Here we review three main roles of astrocytes in ischemic brain damage. First, we consider astrocyte glycogen stores, which can defend the brain against hypoglycemic brain damage but may aggravate brain damage during ischemia due to enhanced lactic acidosis. Second, we review recent breakthroughs in understanding astrocytic mechanisms of transmitter release, particularly for those transmitters with known roles in ischemic brain damage: glutamate, D-serine, ATP and adenosine. Third, we discuss the role of gap-junctionally connected networks of astrocytes in mediating the spread of damaging molecules to healthy ‘bystanders’ during infarct expansion in stroke.

Hanischl and Kettenmann (2007):

Microglia: active sensor and versatile effector cells in the normal and pathologic brainMicroglial cells constitute the resident macrophage population of the CNS. Recent in vivo studies have shown that microglia carry out active tissue scanning, which challenges the traditional notion of ‘resting’ microglia in the normal brain. Transformation of microglia to reactive states in response to pathology has been known for decades as microglial activation, but seems to be more diverse and dynamic than ever anticipated–in both transcriptional and nontranscriptional features and functional consequences. This may help to explain why engagement of microglia can be either neuroprotective or neurotoxic, resulting in containment or aggravation of disease progression. Moreover, little is known about the heterogeneity of microglial responses in different pathologic contexts that results from regional adaptations or from the progression of a disease. In this review, we focus on several key observations that illustrate the multi-faceted activities of microglia in the normal and pathologic brain.

References:Aamodt, Sandra. (2007) Introduction. Nature Neuroscience 10, 1349 (2007) doi:10.1038/nn1107-1349.Hanisch1, Uwe-Karsten and Helmut Kettenmann. (2007) Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nature Neuroscience 10, 1387 – 1394 (2007). Published online: 26 October 2007 | doi:10.1038/nn1997Iadecola, Costantino and Maiken Nedergaard. (2007) Glial regulation of the cerebral microvasculature. Nature Neuroscience 10, 1369 – 1376 (2007). Published online: 26 October 2007 | doi:10.1038/nn2003Miller, Robert and Sha Mi. (2007) Dissecting demyelination. Nature Neuroscience 10, 1351 – 1354 (2007). Published online: 26 October 2007 | doi:10.1038/nn1995.Rossi, David J., James D Brady, and Claudia Mohr. (2007) Astrocyte metabolism and signaling during brain ischemia. Nature Neuroscience 10, 1377 – 1386 (2007). Published online: 26 October 2007 | doi:10.1038/nn2004Scholz, Joachim and Clifford J. Woolf. (2007) The neuropathic pain triad: neurons, immune cells and glia. Nature Neuroscience 10, 1361 – 1368 (2007). Published online: 26 October 2007 | doi:10.1038/nn1992.