Rat brain |
Hypoxia in vivo |
Whole tissue (nmol/g tissue) |
[17] |
Control |
5.4 |
Hypoxia 100N2 90 s |
6.7 ** |
Rat brain |
Brain region (whole tissue) |
Whole tissue (nmol/g tissue) |
[65] |
Thalamus |
9.1 |
Hippocampus |
7.1 |
Cortex |
6.2 |
Cerebellum |
6.1 |
Rat brain slices |
60 min. incubation 31.2 mM K+ |
Brain slices (nmol/g tissue) |
[18] |
Control |
5.04 |
+3-bromorypuvate 0.25 mM |
2.45 |
Rat brain synaptosomes |
30 min. incubation 30 mM K+ |
Synaptosomes Mitochondria Cytoplasm |
[19] |
|
(pmol/mg protein) |
Control |
12.3 46.8 |
+3-bromopyruvate 0.25 mM |
0 7.4 ** |
Healthy adult rat brain synaptosomes |
Healthy control |
Whole synaptosomes (pmol/mg protein) |
[66] different from pyruvate alone, † p < 0.05 |
Substrate used (mM) |
Pyr. 2.5 BHB 2.5 Pyr. + BHB |
24.3 7.1 22.8 |
STZ diabetes 10 d |
31.3 * 10.5 * 29.4 * |
Streptozotocin-diabetic rat brain synaptosomes |
STZ diabetes 10 d + Insulin 5 d |
30.6 * 10.0 *† 35.6 *† |
Cholinergic neuroblastoma cell culture: nondifferentiated (NC) and differentiated (DC, db-cAMP 1 mM + retinoic acid (RA) 0.001 mM 48 h) |
Control |
Cellular compartment levels (pmol/mg protein) |
[67] from respective NC, † p < 0.05, †† p < 0.01 |
Mitochondria Cytoplasm |
NC DC NC DC |
71 22 † 13 50 † |
+NGF 100 ng/mL 24 h |
55 42 ** 71 ** 29 *† |
Native SN56TrkA-/p75NTR+ |
Control |
95 23 † 13 49 † |
Tg T17 SN56TrkA+/p75NTR+ |
+NGF 100 ng/mL 24 h |
59 * 39 * 129 ** 48 † |
Cholinergic neuroblastoma cell culture Tg T17 SN56TrkA+/p75NTR+ NC, and DC |
24 h cell culture with:
|
Relative change against no addition control (%) |
[68][69] Different from respective NC, † p < 0.05, †† p < 0.01; from Aβ (25–35) alone, ‡ p < 0.05, ‡‡ p < 0.01 |
|
Mitochondria Cytoplasm |
NC DC NC DC |
Aβ25-35 0.001 mM |
10 −23 −17 −58 ** |
Acetyl-carnitine 0.1 mM |
+39 ** 0 † 0 +54 **†† |
Aβ + acetyl-carnitine |
+22 ‡‡ 0 0 0 ‡‡ |
ILβ 10 ng/mL |
−11 −18 +38 * −42 *†† |
|
Aβ + ILβ |
−18 −1 +1 +3 ‡‡ |
Cholinergic neuroblastoma cell culture |
ChAT (nmol/min/mg protein) NC DC |
Whole cells (pmol/mg protein) NC DC |
[70] Different from respective native SN56, † p < 0.05, †† p < 0.01 |
Native SN56 TrkA-/p75NTR+ |
0.22 0.79 *** |
31.2 21.9 *** |
Tg T17 TrkA+/p75NTR+ |
0.19 0.47 *** |
39.7 † 26.8 ***† |
Tg ChAT2 TrkA-/p75NTR+ |
3.80 ††† 6.80 ***††† |
15.5 †† 11.2 *** †† |
Cholinergic neuroblastoma cells Native SN56 TrkA-/p75NTR + DC |
24 h cell culture with: Control |
Mitochondria Cytoplasm (pmol/mg protein) |
[40] † different from ZnCl2 0.10 mmol/L |
11.8 20.9 |
ZnCl2 0.10 mM |
9.3 19.6 |
ZnCl2 0.15 mM |
11.4 13.5 *† |
Cholinergic neuroblastoma cells Native SN56 TrkA-/p75NTR + NC and DC |
30 min incubation (protein free medium) with: Zn 0.1 mM |
Relative change vs. no Zn control (%) Mitochondria Cytoplasm NC DC NC DC −5 −35 ** −100 ** −80 ** |
[71] |
Subcutaneous pyrithiamine (PT) 0.025 mg/kg b.w./day and thiamine free diet 14 d Rat forebrain synaptosomes |
PT synaptosomes vs. no PT control |
Forebrain synaptosomesRelative change against no PT control (%) |
[72] |
|
Mitochondria Cytoplasm |
No Ca Ca 1.0mM no Ca Ca1.0mM |
−53 *** −35 *** −43 *** −24 * |
Subcutaneous PT 0.025 mg/kg b.w./day and thiamine-free diet 14 d. Rat forebrain whole mitochondria |
PT whole forebrain mitochondria vs. no PT control |
Forebrain whole mitochondria Relative change vs. no PT control (%) |
[73] |
No Ca Ca 0.01 mM ADP/HX |
−62 *** −62 *** −52 *** |
Cholinergic neuroblastoma cell culture Native SN56 TrkA-/p75NTR+ |
Thiamine-free culture medium 48 h +Amprolium 2 mM |
Relative change vs. no amprolium NC control (%) |
[74] Amprolium suppressed TPP level—28% vs. control |
Mitochondria Cytoplasm. |
NC DC NC DC |
−43 −57 −58 *** −50 ** |
Endoplasmic reticulum from WT and AT 1-1S113R/+ mice |
Mutation AT 1-1S113R/+ |
Acetyl-CoA transport (pmol/mg/5 min.) |
[75] |
WT 370 |
AT-1S113R/+ 142 *** |
N9 microglioma cells culture |
24 h culture with:
LPS 0.01 µg/mL |
Relative change against respective no addition control (%) |
[38] ‡‡ different from SNP 0.4 mM, p < 0.01 ††† different from N9 cells, p < 0.001 |
Whole cells |
N9 SN56 |
−23 * +4 |
SynchronizedCholinergic neuroblastoma cells Native SN56 TrkA-/p75NTR+ DC |
SNP 0.4 mM |
−3 −38 * |
LPS + SNP |
−6 92 ***†††‡‡ |
WT 14–16 mos mouse brain AβPP-Tg 2576 14-16 m mouse brain |
Accumulation about 0.6 μM Aβ1-42 in Tg brain |
Relative change vs. WT control (%) Mitochondria Cytoplasm ** |
[62] Acetyl-CoA—control WT mice Synapt. mitoch. 39 pmol/mg prot. Synapt. cytopl. 90 pmol/mg prot. Whole brain mitoch. 45 pmol/mg. |
Forebrain synaptosomes |
−44 ** −34 |
Forebrain whole mitochondria |
+5 - |
WT mouse brain AT1 Tg mouse brain (overexpression) |
Hippocampus Isolated adult neurons H4 neuroglioma |
AT1 Tg vs. WT Relative difference (%) Cytoplasm |
[76] |
−41 * |
−45 * |
−43 * |
WT 9 d postnatal mouse brain |
24 h post hypoxia/ischemia |
Relative change vs. control (%) Mitochondrial fraction Vehicle-treated DCA-treated +6 +27 * |
[34] |
Cell line cultures WT SN56 TrkA-/p75NTR NC |
Intracellular Zn accumulation of 5 nmol/mg protein at extracellular Zn in culture medium: 0.125 mM |
Relative change vs. no Zn control (%) SN56 NC −54 *** |
[11] † different from NC, p < 0.05 |
DC |
0.110 mM |
SN56 DC −48 ***† |
SHSY5Y dopaminergic neurons |
0.150 mM |
SHSY5Y −31 * |
C6 astroglioma |
0.200 mM |
C6 −44 ** |
3XTg AD 16.5 mos mouse brain |
8 mos ketone ester-feeding |
Relative change vs. non-ketotic control (%) Hippocampus +79 * |
[77] Acetyl-CoA no ketone control: 17 μmol/g tissue |
Mouse BV2 microglial cells culture |
Dimethylsulfoxide-induced 6 h hypoxia |
Relative change vs. no hypoxia control (%) +79 ** |
[30] |
Hypoxia + Lonidamine 0.05 mM |
−58 * |
Hypoxia + 3-Bromopuryvate |
−42 * |
Cholinergic neuroblastoma cells WT SN56 TrkA-/p75NTR+ DC |
30 min incubation (protein-free medium) with: Control Nifedipine 0.01 mM GVIA 0.0005 mM MVIIC 0.0002 mM |
Whole cells (pmol/mg protein) No Zn Zn 0.15 mM 30.5 13.8 * 30.7 29.2 † 28.8 21.6 *† 28.1 20.5 *† |
[78] Compounds used here are inhibitors of different types of calcium channels. * p < 0.01 vs. no Zn control; † < 0.01 vs. 0.15 mM Zn. |
SAMP8 mice brain cortex |
13 mos vs. 9 mos change
No treatment
Fed with CMS121 4 mos
Fed with J147 4 mos |
Relative change 13 mos vs. 9 mos |
[79] CMS121, J147 are acetyl-CoA carboxylase inhibitors. |
(%) |
−41 **** |
−12 |
−6 |
HT22 hippocampal neuronal cell culture
Primary E21 mice neuronal culture |
24 h culture with: |
Relative change vs. no addition control (%) |
[10][79] Compounds used here inhibit acetyl-CoA carboxylase by different mechanisms. |
+ACC1 siRNA |
+114 *** |
+TOFA 0.01 mM |
+178 *** |
+CMS 121 0.001 mM |
+140 *** |
+J147 0.001 mM |
+100 ** |
+CAD031 0.001 mM |
+177 *** |
|
|
+CMS 121 0.001 mM |
+57 *** |
+J147 0.001 mM |
+29 |
+CAD031 0.001 mM |
+108 *** |
Brain-specific pdha1flox8/wt deficient mice (PDHD) |
PDHD |
Relative change vs. control (%) −12 |
[54] |
3xTgAD mice WT control mice |
Ageing—2, 11, 21 mos hippocampus whole tissue
Control |
2 mos 11 mos 21 mos |
[80] Different from the corresponding 2 mos mice, † p < 0.05, ††† p < 0.001 |
(Arbitrary units) |
Male |
0.5 1.1† 1.3 ††† |
3XTgAD |
1.2 * 1.6 * 2.6 **††† |
|
Female |
Control |
0.5 0.8 1.0 † |
3XTgAD |
0.5 1.3 *† 1.2 † |
Rat permanent middle cerebral artery occlusion model of brain stroke (pMCAO) |
Shengui Shanseng San (SSS) extraction feeding per os 3 d before and 7 d after pMCAO |
Relative change vs. sham control |
[35] Absolute sham control value of infarct-corresponding control region equal to 24.4 µmol/µL tissue is 106 times higher than those reported elsewhere. |
In brain infarcted region (%) pMCAO −80 *** |
Low dose SSS + pMCAO −52 *** |
Middle dose SSS +pMCAO −44 *** |
High dose SSS +pMCAO −4 |
Closed-head impact acceleration model of mild or severe traumatic rat brain injury (mTBI/sTBI) |
mTBI/sTBI |
Relative change vs. control (%) Whole brain extracts |
[58] Absolute control value about 39 nmol/g wet weight is about 10 times higher than values reported elsewhere. Different from the corresponding of post mTBI time, † p < 0.005 |
Post mTBI 6 h −13 |
24 h −22 |
48 h −24 |
120 h −13 |
Post sTBI 6 h −34 * |
24 h −56 *† |
48 h −47 *† |
120 h −58 *† |
HEK293 cell culture |
DIP2A overexpression |
Relative change DIP2A vs. no insert control (%) +120 * |
[81] |
Traumatic brain injury/control cortical impact rat brain (TBI/CCI) |
TBI/CCI |
Peri-contusional brain cortex acetyl-CoA (ng/mg protein) Early immediate 3 h i.v. administration |
[41] Absolute control value is about 34.5 pmol/mg protein. |
Sham (saline 0.9%) 27 |
Control 38 |
Glucose 30% 57 * |
Lactate 100 mM 29 |
BHB 2M 52 * |
Late (6 h post impact) 3 h i.v. administration |
Glucose 30% 38 |
Lactate 100 mM 21 |
BHB 2M 38 |
Cholinergic neuroblastoma cells WT SN56 TrkA-/p75NTR+ DC |
30 min incubation (protein-free medium) with: |
Relative change vs. control (%) Mitochondria Cytoplasm |
[82] Mecamylamine is a nonselective antagonist of nicotinic receptors. 2APB is inhibitor of IP3 receptors and TRP channels. |
Mecamylamine 0.002 mM |
−36 ** +7 |
Nifedipine 0.01 mM |
0 +28 |
2-Aminoethoxydiphenyl borate (2-APB) 0.05 mM |
+43 -56 ** |
Zn 0.15 mM |
−64 *** −39 ** |
Human fibroblastoma HT1080 cell line ACLY WT ACLY-WT ACLY KO |
4 h incubation with or without 20 mM acetate
ACLY-WT ACLY-KO |
Relative change vs. WT-acetate control (%) |
[83] Absolute control value for ACLY-WT is 6.1 μM (normalised to internal standard) |
acetate 20 mM No acetate |
0 −14 |
−67 *** −95 *** |
E18 C57BL/6J mice model of AD |
24 h culture with Aβ1-42 10µM |
Relative change vs. control (%) |
[84] Absolute control values for neurons and microglia are 0.45 and 0.75 μM, respectively |
Neurons Microglia ** |
0 −31 |
5XFAD 9 mos mouse brain |
5XFAD control 5XFAD + efavirenz 0.1 mg/kg b.w./d in drinking water from 3 to 9 mos of life |
Whole brain Mitochondria (pmols/mg protein) |
[85] Efavirenz is an inhibitor of reverse transcriptase. Acetyl-CoA control levels reported here are about 10 times higher than reported elsewhere. |
145 87 |
351 *** 352*** |
B6SJ/L 9 months mouse brain |
B6SJ/L control |
361 157 |
Tg Cyp46a1+/+ |
Tg Cyp46a1+/+ |
257 *** 128 |
Tg Cyp46a1−/− |
Tg Cyp46a1−/− |
143 *** 100 *** |
Cholinergic neuroblastoma cells
WT SN56 TrkA-/p75NTR+ NC and DC |
24 h culture in thiamine-free medium with:
+Zn 0.1 mM +Amprolium 5 mmol/L +Zn +Amprolium |
Relative change vs. no Zn, and amprolium control (%) Mitochondria |
[45] Absolute control acetyl-CoA levels in NC and DC mitochondria were: 11.6 and 11.9 pmol/mg protein, respectively. Absolute control acetyl-CoA levels in NC and DC cytoplasm were: 13.6 and 11.7 pmol/mg protein, respectively. †† different from NC/DC Zn, p < 0.0.1 different from NC/DC amprolium, ‡ p < 0.05, ‡‡ p < 0.01 |
NC DC |
−5 −23 ** |
−5 −16 * |
−45 ***††‡‡ -50 **††‡‡ |
Cytoplasm |
+Zn 0.1 mM |
−4 −12 |
+Amprolium 5 mmol/L |
−17 −12 |
Thiamine-deficient culture medium |
+Zn +Amprolium |
−54 **††‡‡ −53 **††‡‡ |
C6 astroglioma cells
Cholinergic neuroblastoma cells WT SN56 TrkA-/p75NTR+ DC |
24 h culture C6 in thiamine-free or thiamine-supplemented medium with:
Amprolium 10 mM Zn 0.15 mM Zn 0.20 mM
24 h culture SN56 in thiamine-free medium in co-culture with C6 C6 co-culture Amprolium 5 mM Zn 0.1 mM Amprolium + Zn Amprolium + Zn+C6 co-culture |
Relative change vs. no Zn, no amprolium control (%) Thiamine deficient Thiamine suppl. |
[39] Absolute control levels of acetyl-CoA in SN56 and C6 cells were: 27.2 and 14.6 pmol/mg protein, respectively. † different from Amprolium+Zn, p < 0.05 |
−26 ** 0 |
−28 −16 |
−68 ** −56 ** |
Relative change vs. no co-culture, Zn, and no amprolium control (%) |
+10 |
−26 |
−29 |
−64 * |
−10 † |
WT mouse brain C57BL/6J mouse brain |
Glycerol triacetate 3 g/kg b.w./d 10 d by gavage, and euthanised 60 min. post last gavage |
Hippocampus Relative change vs. control (%) |
[86] |
Whole tissue Nuclei Cytoplasm |
|
+171 * +19 *** +13 ** |
Non-fasted mouse brain |
Sacrificed 30 min. post oral ketone esters (KE) administration 3 mg/g b.w |
Relative change KE vs. control (%) Brain cortex +114 *** |
[87] |
Cultured primary neurons (E17 C57BL/6J mice) |
Astrocyte-derived ApoE particles
Astrocyte-derived medium (ADM)Apo E enriched ADMApo E depleted ADM |
Relative change vs. no ApoE control (%) Acetyl-CoA/CoA ratio Whole cells Nuclei +86 * +175 *** Acetyl-CoA/CoA ratio +200 *** +40 |
[32] |
WT mouse brain Elp3 conditional KO mouse brain |
Lack Elongator to Atat1 activity |
Relative change vs. WT control (%) Cortical neurons−72 |
[88] |
WT mouse brain C57Bl/6J mouse brain |
Acute stress |
Relative change vs.no stress control (%) Prefrontal cortex +113 * |
[89] Absolute acetyl-CoA level, 0.37 pmol/μg |
C57BL/6J mice—stroke and hypoxia |
12 wk post-stroke oral administration p75 NTR modulator (LM11A-31) |
Relative change vs. sham control (%) Brain infarcted region None LM11A-31 −32 +36 * |
[23] |
Primary astrocytes—0–1-day-old mice cerebral cortex
U87 human glioblastoma cells U87FABP7wt U87FABPmut. U251human glioma cells U251 FABP7KO |
FABP7-KO vs. WT cells
FABP7wt vs. control FABP7mut vs. control
FABP7KO vs. control |
Relative change vs. WT control (%) Whole cells Isolated nuclei −34 * −28 *
+87 * +74 * −10 −39
−48 * −70 * |
[90][91] Absolute acetyl-CoA for control WT cells is 450 pmol/106, and 74 pmol/107 nuclei. |
WT mouse brain SLC25A1 nTg mouse brain |
Hippocampus and cortex cytoplasm
Lumen of the endoplasmic reticulum |
Relative change vs. WT control (%) Cytoplasm ER +58 *** +72 **** |
[92] SLC25A1 nTg—mitochondrial citrate carrier |