Marchiafava-Bignami disease with dementia: Severe cerebral metabolic depression revealed by PET

Poikilotherms and homeotherms have different, well-defined metabolic responses to ambient temperature (Ta), but both groups have high power costs at high temperatures. Sloths (Bradypus) are critically limited by rates of energy acquisition and it has previously been suggested that their unusual departure from homeothermy mitigates the associated costs. No studies, however, have examined how sloth body temperature and metabolic rate vary with Ta. Here we measured the oxygen consumption (VO2) of eight brown-throated sloths (B. variegatus) at variable Ta’s and found that VO2 indeed varied in an unusual manner with what appeared to be a reversal of the standard homeotherm pattern. Sloth VO2 increased with Ta, peaking in a metabolic plateau (nominal ‘thermally-active zone’ (TAZ)) before decreasing again at higher Ta values. We suggest that this pattern enables sloths to minimise energy expenditure over a wide range of conditions, which is likely to be crucial for survival in an animal that operates under severe energetic constraints. To our knowledge, this is the first evidence of a mammal provisionally invoking metabolic depression in response to increasing Ta’s, without entering into a state of torpor, aestivation or hibernation.

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A MICROCALORIMETRIC STUDY OF TURTLE CORTICAL SLICES: INSIGHTS INTO BRAIN METABOLIC DEPRESSION

Journal of Experimental Biology ◽

10.1242/jeb.191.1.141 ◽

1994 ◽

Vol 191 (1) ◽

pp. 141-153 ◽

Cited By ~ 1

Author(s):

C Doll ◽

P Hochachka ◽

S Hand

Keyword(s):

Cortical Neurons ◽

Heat Dissipation ◽

Energy Charge ◽

Utilization Rate ◽

Rapid Decline ◽

Metabolic Depression ◽

Slice Preparation ◽

Cortical Slices

In previous papers, we have examined turtle cortical neurons in vitro for mechanisms of anoxic metabolic depression ('channel arrest' and changes in electrical parameters). Negative results prompted the current study with the aim of examining more closely the energy profile and metabolism of turtle cortical slices. Calorimetry is used to measure heat dissipation during normoxia and nitrogen perfusion (120 min) and the results are converted into an ATP utilization rate. These indicate that the control rate of ATP utilization (1.72 µmol ATP g-1 min-1) agrees closely with in vivo whole-brain metabolic measurements. Both nitrogen perfusion and pharmacologically induced anoxic (cyanide+N2) groups depressed heat dissipation considerably compared with the control value (nitrogen 37 %; pharmacological anoxia 49 %). The resulting ATP utilization estimates indicate metabolic depressions of 30 % (nitrogen) and 42 % (pharmacological anoxia). The slice preparation did not exhibit a change in any measured adenylate parameter for up to 120 min of anoxia or pharmacological anoxia. Significant changes did occur in [ADP], ATP/ADP ratio and energy charge after 240 min of exposure to anoxic conditions. These results support the idea that the turtle cortical slice preparation has a profound resistance to anoxia, with both nitrogen perfusion and pharmacological anoxia causing a rapid decline in heat dissipation and metabolism.

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Modulation of the cost of pHi regulation during metabolic depression: a (31)P-NMR study in invertebrate (Sipunculus nudus) isolated muscle

Journal of Experimental Biology ◽

10.1242/jeb.203.16.2417 ◽

2000 ◽

Vol 203 (16) ◽

pp. 2417-2428 ◽

Cited By ~ 6

Author(s):

H.O. Portner ◽

C. Bock ◽

A. Reipschlager

Keyword(s):

Steady State ◽

Marine Invertebrate ◽

Metabolic Depression ◽

Acid Base ◽

Extracellular Acidosis ◽

Nmr Study ◽

Sipunculus Nudus ◽

Delayed Recovery ◽

Dimethyl Amiloride

Extracellular acidosis has been demonstrated to play a key role in the process of metabolic depression under long-term environmental stress, exemplified in the marine invertebrate Sipunculus nudus. These findings led to the hypothesis that acid-base regulation is associated with a visible cost depending on the rate and mode of H(+)-equivalent ion exchange. To test this hypothesis, the effects of different ion-transport inhibitors on the rate of pH recovery during hypercapnia, on energy turnover and on steady-state acid-base variables were studied in isolated body wall musculature of the marine worm Sipunculus nudus under control conditions (pHe 7.90) and during steady-state extracellular acidosis (pHe 7.50 or 7.20) by in vivo (31)P-NMR and oxygen consumption analyses. During acute hypercapnia (2 % CO(2)), recovery of pHi was delayed at pHe 7.5 compared with pHe 7.9. Inhibition of the Na(+)/H(+)-exchanger by 5-(N,N-dimethyl)-amiloride (DMA) at pHe 7.5 delayed recovery even further. This effect was much smaller at pHe 7.9. Inhibition of anion exchange by the addition of the transport inhibitor 4, 4′-diisothiocyanatostilbene-2,2′-disulphonic acid (DIDS) prevented pH recovery at pHe 7.5 and delayed recovery at pHe 7.9, in accordance with an effect on Na(+)-dependent Cl(−)/HCO(3)(−) exchange. The effects of ouabain, DIDS and DMA on metabolic rate were reduced at low pHe, thereby supporting the conclusion that acidosis caused the ATP demand of Na(+)/K(+)-ATPase to fall. This reduction occurred via an inhibiting effect on both Na(+)/H(+)- and Na(+)-dependent Cl(−)/HCO(3)(−) (i.e. Na(+)/H(+)/Cl(−)/HCO(3)(−)) exchange in accordance with a reduction in the ATP demand for acid-base regulation during metabolic depression. Considering the ATP stoichiometries of the two exchangers, metabolic depression may be supported by the predominant use of Na(+)/H(+)/Cl(−)/HCO(3)(−) exchange under conditions of extracellular acidosis.

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