Could inhibiting or functionally removing the brain’s suprachiasmatic nucleus improve memory in elderly people — who have chronic problems sleeping? — A finding in Siberian hamsters hints “maybe”

© 2014 Peter Free

Citation — to study

Fabian Fernandez, Derek Lu, Phong Ha, Patricia Costacurta, Renee Chavez, H. Craig Heller, and Norman F. Ruby, Dysrhythmia in the suprachiasmatic nucleus inhibits memory processing, Science 346(6211): 854-857, DOI: 10.1126/science.1259652 (14 November 2014)

Citation — to press release

Bjorn Carey, Stanford biologists explore link between memory deficit and misfiring circadian clock, Stanford University (17 November 2014)

Method and findings

From the abstract:

Chronic circadian dysfunction impairs declarative memory in humans . . . . [H]uman dysrhythmia occurs while SCN [suprachiasmatic nucleus] circuitry is genetically and neurologically intact.

Siberian hamsters (Phodopus sungorus) are particularly well suited for translational studies because they can be made arrhythmic by a one-time photic [light] treatment that severely impairs spatial and recognition memory.

We found that once animals are made arrhythmic, subsequent SCN ablation [destruction] completely rescues memory processing.

© 2014 Fabian Fernandez, Derek Lu, Phong Ha, Patricia Costacurta, Renee Chavez, H. Craig Heller, and Norman F. Ruby, Dysrhythmia in the suprachiasmatic nucleus inhibits memory processing, Science 346(6211): 854-857, DOI: 10.1126/science.1259652 (14 November 2014) (at Abstract) (extracts)

More detail

From Bjorn Carey’s excellent press release:

[T]hey trained Siberian hamsters in a standard learning and memory task, which involved familiarizing them with two objects and then, some time later, changing up one of the objects and seeing if the rodents noticed. On the whole, the animals excelled at the test.

Once the animals had mastered the task, the researchers exposed them to light at odd intervals, which threw off their circadian rhythms. The arrhythmic hamsters were then given the same memory task, and failed miserably.

Next, the researchers surgically removed each hamsters’ SCN . . . and gave the memory test a third time . . . . [T]he animals performed the test as well as they had at the beginning of the experiment.

Elderly people with neurodegenerative memory deficiencies also often complain of poor sleep, which can be associated with weakened circadian timing.

The new work suggests that rather than repairing the systems responsible for a misfiring SCN, it might be more productive to simply remove it from the equation.

“The more I investigate it, the idea of shutting off the SCN as a way of restoring memory ability in humans seems more provocative and possibly doable,” Ruby said. “If you are treating a a neurodegenerative brain, rather than fixing the circadian clock, it might be easier to just pharmacologically shut down the SCN.”

© 2014 Bjorn Carey, Stanford biologists explore link between memory deficit and misfiring circadian clock, Stanford University (17 November 2014) (extracts)

Caveat

Without a gram of belittlement intended, the suprachiasmatic nucleus probably controls a good deal more than we recognize. Taking it out of the “circuit” may create more problems than it solves.

I am also not convinced that there is a substantial subset among the elderly population, who simply have a circadian rhythm problem that is not accompanied by a wider neuro-degenerative one. The latter might itself account for the inability to drag an even adequately formed memory out of storage in useable form.

The moral? — Excellent work and a promising avenue of further investigation

My caveats may be completely wrong and are not intended to slight the worth of this clever study.

Comparing actual past ecological niches — to those predicted by backward looking climate models — has apparently demonstrated that existing models move species too far south — during the Last Glacial Maximum

© 2014 Peter Free

Citation — to study

Edward Byrd Davis, Jenny L. McGuire, and John D. Orcutt, Ecological niche models of mammalian glacial refugia show consistent bias, Ecography 37(11): 1133–1138, DOI: 10.1111/ecog.01294 (November 2014)

Citation — to press release

Jim Barlow, Fossils cast doubt on climate-change projections on habitats, University of Oregon (18 November 2014)

Past animal biology appears to have known something that we don’t

From the abstract:

Ecological niche models (ENMs) are crucial tools for anticipating range shifts driven by climate change. As hypotheses of future biotic change, they can be difficult to test using independent data.

The fossil record is the best way to assess the ability of ENMs to correctly predict range shifts because it provides empirical ranges under novel climate conditions.

We tested the performance of ENMs using fossil distributions from the Last Glacial Maximum (LGM, ∼21 000 yr ago).

We compared hindcast [backward looking] ENM LGM distribution hypotheses for five species of small mammals, drawn from the published literature, to the known LGM fossil record for those species and found a consistent southern prediction bias in the ENMs.

This bias urges caution in interpreting future range predictions, and we suggest that the Pleistocene and Holocene fossil record should be used as an additional resource for calibrating niche modelling for conservation planning.

© 2014 Edward Byrd Davis, Jenny L. McGuire, and John D. Orcutt, Ecological niche models of mammalian glacial refugia show consistent bias, Ecography 37(11): 1133–1138, DOI: 10.1111/ecog.01294 (November 2014) (at Abstract) (paragraph split)

Thus,

Blarina brevicauda (northern short-tailed shrew),

Martes americana (American pine marten),

Glaucomys sabrinus (northern flying squirrel),

Glaucomys volans (southern flying squirrel),

and

Myodes gapperi (Gapper’s or southern red backed vole) —

all lived farther north (and closer to the ice) than anticipated by niche-predicting models.

Why the error?

The authors suggest that:

In the end, we propose four possible causes for these patterns of biased prediction:

1) [M]odern distributions may not reflect the full range of environmental conditions in which a species can survive and, taken alone, serve as poor predictors of their potential distributions under other climate regimes.

2) The environmental tolerances of mammalian species can evolve fast enough to have changed since the LGM [Last Glacial Maximum], so modern distributions are poor predictors of deeper time distributions, but may still be good predictors of shallow time responses to climate change.

3) The problem lies with the general circulation models (GCMs) used to reconstruct LGM climate, so the reconstructed ranges are biased southwards because of incorrect temperature and/or precipitation values near the continental glaciers.

4) The models used to hindcast ranges are based on correlations between climatic variables and occurrence data in modern ecosystems.

[C]hanging distribution and relationships between climatic variables mean that modern ecosystems may not be appropriate analogs for alternative climatic regimes, such as those that existed during the LGM and that may result from future warming.

© 2014 Edward Byrd Davis, Jenny L. McGuire, and John D. Orcutt, Ecological niche models of mammalian glacial refugia show consistent bias, Ecography 37(11): 1133–1138, DOI: 10.1111/ecog.01294 (November 2014) (at Discussion, second to last paragraph) (extracts)

The moral? — We don’t know “squat”

Which is why I occasionally get irritated with the high levels of certainty that some modelers seem to extrapolate from their concocted guesses about (a) climate change and (b) its past and future effects on all manner of things.

Just because we know that warming is occurring (and generally why) does not mean that we can (today) reliably predict its consequences under complex past or future conditions.

Myocardial infraction (heart attack) is apparently characterized by 2 — not 1 — stages of edema after reperfusion in pigs — says a small study — are humans the same?

© 2014 Peter Free

Citation — to study

Rodrigo Fernández-Jiménez, Javier Sánchez-González, Jaume Aguero, Jaime García-Prieto, Gonzalo J. López-Martín, José M. García-Ruiz, Antonio Molina-Iracheta, Xavier Rosselló, Leticia Fernández-Friera, Gonzalo Pizarro, Ana García-Álvarez, Erica Dall’Armellina, Carlos Macaya, Robin P. Choudhury, Valentin Fuster, and Borja Ibanez, Myocardial Edema After Ischemia/Reperfusion Is Not Stable and Follows a Bimodal Pattern: Advanced Imaging and Histological Tissue Characterization, Journal of the American College of Cardiology, DOI:10.1016/j.jacc.2014.11.004 (in press, 17 November 2014)

Goal, method and results

The research team wanted to shed light on the phenomenon of edematous heart muscle after myocardial infarction.

From the abstract:

The study population consisted of 25 instrumented Large-White pigs (30-40 Kg).

Closed-chest 40min ischemia/reperfusion was performed in 20 pigs, which were sacrificed at 120 minutes (n=5), 24 hours (n=5), 4 days (n=5) and 7 days (n=5) after reperfusion and processed for histological quantification of myocardial water content.

Cardiac magnetic resonance (CMR) scans with T2W-STIR and T2-mapping sequences were performed at every follow-up stage until sacrifice.

Five additional pigs sacrificed after baseline CMR served as controls.

Contrary to the accepted view, myocardial edema during the first week after ischemia/reperfusion follows a bimodal pattern.

The initial wave appears abruptly upon reperfusion and dissipates at 24 hours. Conversely, the deferred wave of edema, appears progressively days after ischemia/reperfusion and is maximal around day 7 after reperfusion.

© 2014 Rodrigo Fernández-Jiménez, Javier Sánchez-González, Jaume Aguero, Jaime García-Prieto, Gonzalo J. López-Martín, José M. García-Ruiz, Antonio Molina-Iracheta, Xavier Rosselló, Leticia Fernández-Friera, Gonzalo Pizarro, Ana García-Álvarez, Erica Dall’Armellina, Carlos Macaya, Robin P. Choudhury, Valentin Fuster, and Borja Ibanez, Myocardial Edema After Ischemia/Reperfusion Is Not Stable and Follows a Bimodal Pattern: Advanced Imaging and Histological Tissue Characterization, Journal of the American College of Cardiology, DOI:10.1016/j.jacc.2014.11.004 (in press, 17 November 2014) (at Abstract) (extracts)

The moral? — A worthy study

Pig hearts are similar to humans’. Therefore, human beings may experience a similar bimodal, edematous reperfusion response. If so, this might be an important finding, provided that:

edema and inflammation go hand and hand (as they almost certainly do here),

and

inflammation is bad for recovering cardiac muscle (as most think it is),

and

researchers can figure out (i) when and (ii) how to intervene to ameliorate one or both waves of edematous inflammation.

Third-day subsequent brain re-injury can increase insulin resistance in mouse brains — thereby reducing their ability to heal

© 2014 Peter Free

Citation — to study

Zachary M. Weil, Kristopher R. Gaier, and Kate Karelina, Injury timing alters metabolic, inflammatory and functional outcomes following repeated mild traumatic brain injury, Neurobiology of Disease70: 108-116, DOI:10.1016/j.nbd.2014.06.016 (October 2014)

If human brains are similar, this study is important for designing post-concussion protocols

From the excellent abstract:

There is ample experimental and clinical evidence that there is a period of enhanced vulnerability to subsequent injury following head trauma.

Injuries that occur close together in time produce greater cognitive, histological, and behavioral impairments than do injuries separated by a longer period.

Traumatic brain injuries alter cerebral glucose metabolism and the resolution of altered glucose metabolism may signal the end of the period of greater vulnerability.

Here, we injured mice either once or twice separated by three or 20 days.

Repeated injuries that were separated by three days were associated with greater axonal degeneration, enhanced inflammatory responses, and poorer performance in a spatial learning and memory task.

A single injury induced a transient but marked increase in local cerebral glucose utilization in the injured hippocampus and sensorimotor cortex, whereas a second injury, three days after the first, failed to induce an increase in glucose utilization at the same time point.

In contrast, when the second injury occurred substantially later (20 days after the first injury), an increase in glucose utilization occurred that paralleled the increase observed following a single injury.

The increased glucose utilization observed after a single injury appears to be an adaptive component of recovery, while mice with 2 injuries separated by three days were not able to mount this response, thus this second injury may have produced a significant energetic crisis such that energetic demands outstripped the ability of the damaged cells to utilize energy.

These data strongly reinforce the idea that too rapid return to activity after a traumatic brain injury can induce permanent damage and disability, and that monitoring cerebral energy utilization may be a tool to determine when it is safe to return to the activity that caused the initial injury.

© 2014 Zachary M. Weil, Kristopher R. Gaier, and Kate Karelina, Injury timing alters metabolic, inflammatory and functional outcomes following repeated mild traumatic brain injury, Neurobiology of Disease70: 108-116, DOI:10.1016/j.nbd.2014.06.016 (October 2014) (paragraph split)

The moral? — As a parent, I would be treating this as true, until proven otherwise

The study also reminds us of the difficult ethics of doing medical research on animals.

Satellite transmitters attached to five southern right whales (Eubalaena australis) — may help biologists figure out why individuals have been dying at high rates

© 2014 Peter Free

Citation — to press release

Wildlife Conservation Society, Scientists employ satellite tags to solve whale-sized mystery, ScienceDaily (14 November 2014)

The survival problem

From the press release:

Over the past decade, southern right whale [see here] calves have died in unprecedented numbers (more than 400 between 2003-2011) for reasons still unclear to scientists. Different hypotheses for this mortality have been considered, including disease, certain types of contaminant, and harassment and wounding by kelp gulls, a frequent occurrence in Península Valdés [see here].

This new research will help assess where the whales are feeding, namely if there could be any threats to the whales along their migration route or on their feeding grounds and if the research team can conduct additional tagging and studies to determine any issues associated with food or nutritional stress causing calf loss by some mothers.

© 2014 Wildlife Conservation Society, Scientists employ satellite tags to solve whale-sized mystery, ScienceDaily (14 November 2014)

The investigative solution

Simple enough in concept, difficult to implement:

Over the past month, the team succeeded in affixing satellite transmitters to five southern right whales . . . .

The deployed tags will transmit the geographical position and behavioral information of the animals up to Earth-orbiting satellites multiple times a day, allowing researchers to follow whales remotely.

The researchers selected calving females and solitary juveniles for satellite tagging in order to glean insights into habitat use and migratory movements for different sex and age groups.

Sais Alex Zerbini, a whale telemetry expert from NOAA . . . :

“Tagging individuals of different sex and age classes will let us explore potential differences in how they migrate and use their habitats.”

© 2014 Wildlife Conservation Society, Scientists employ satellite tags to solve whale-sized mystery, ScienceDaily (14 November 2014) (extracts)

Caveat

Knowing where the whales go will not be enough. Obviously, one will have to determine why so many are dying from which causes. That is going to require post mortems of carcasses, as well as visits to the geographical sites where the presumed agents of causation hypothetically originated.

The moral? — A great start

The teams will probably have to track more than 5 whales to have much hope of concluding a successful investigation of the causes for the apparently increased mortality rate among the whales.

The work must be exhilarating for people who love animals, dangerous outdoors and mysteries. I am envious.