Table 2.
The Germ-Free Physiological Profile
| Category | Parameter | Phenotype | Strain and Sex | Tissue/Brain Region | Reversible? | Reference |
|---|---|---|---|---|---|---|
| Neurological disease- related effects | Amyloid-β | Decreased amyloid-β pathology | APPPS1 transgenic on C57BL/6 background (m & f) | Brain | Yes, only if colonized with SPF APPPS1 mouse microbiota | Harach et al., 2015 |
| EAE | Fully protected against developing EAE | SJL/J | CNS and immune tissue | Yes | Berer et al., 2011 | |
| EAE | Highly resistant to EAE | C57BL6/J (f) | CNS and immune tissue | Yes | Lee et al., 2011 | |
| Neuronal activity, plasticity & survival | Neuronal Activity | Decreased c-Fos expression after 1 hour of stress | Swiss Webster (f) | CA1 of the hippocampus | Gareau et al., 2011 | |
| Neurogenesis | Increased cell and neuron survival | Swiss Webster | Subgranular zone of the hippocampus | No | Ogbonnaya et al., 2015 | |
| Synapse-related genes | Decreased synaptophysin and PSD- 95 expression | NMRI (m) | Striatum | Heijtz et al., 2011 | ||
| Transcriptome | Differential expression | NMRI (m) | Cerebellum > hippocampus > striatum > cortex | Heijtz et al., 2011 | ||
| Transcriptome | Upregulation of genes associated with neuronal activity | Swiss Webster (m) | Amygdala | No | Stilling et al., 2015 | |
| Neuroprotection | Blood brain barrier | Increased permeability | NMRI (m) | – | Braniste et al., 2014 | |
| Microglia | Impaired immune response and immature morphology | C57BL/6 (m, f) | Corpus callosum, cortex, hippocampus, olfactory bulb, cerebellum | Yes | Erny et al., 2015 | |
| Neurotransmission | Dopamine receptor | Increased Drd1a expression | NMRI (m) | Hippocampus | Heijtz et al., 2011 | |
| Glutamate receptor | Decreased Nr1 expression | BALB/c (m) | Cortex | Sudo et al., 2004 | ||
| Glutamate receptor | Decreased Nr2 expression | BALB/c (m) | Cortex, hippocampus | Sudo et al., 2004 | ||
| Glutamate receptor | Decreased Nr2 expression | Swiss Webster (f) | Central nucleus of the amygdala | Neufeld et al., 2011 | ||
| Kynurenine:tryptophan ratio | Decreased kynurenine:tryptophan ratio | Swiss Webster (m, f) | Blood: plasma | Yes | Clarke et al., 2013 | |
| Monoamine Turnover | Increased turnover of noradrenaline, dopamine, and serotonin | NMRI (m) | Striatum | Heijtz et al., 2011 | ||
| Serotonin | Increased CNS serotonin levels | Swiss Webster (m) | Hippocampus | No | Clarke et al., 2013 | |
| Serotonin | Decreased peripheral serotonin levels | C57BL/6 | Colon | Yes | Yano et al., 2015 | |
| Serotonin Receptor | Decreased Htr1a expression | Swiss Webster (f) | Dentate gyrus of the hippocampus | Neufeld et al., 2011 | ||
| Tryptophan | Increased levels of tryptophan | Swiss Webster (m) | Blood: plasma | Yes | Clarke et al., 2013 | |
| Neurotrophin expression | BDNF | Reduced Bdnf expression | Swiss Webster (m) | Amygdala | Arentsen et al., 2015 | |
| BDNF | Reduced Bdnf expression | Swiss Webster (m) | Hippocampus | Clarke et al., 2013 | ||
| BDNF | Reduced BDNF expression | Swiss Webster (f) | CA1 of the hippocampus | Gareau et al., 2011 | ||
| BDNF | Reduced Bdnf expression | NMRI (m) | Basolateral amygdala, CA1 of the hippocampus, cingulate cortex | Heijtz et al., 2011 | ||
| BDNF | Increased Bdnf expression | Swiss Webster (f) | Dentate gyrus of the hippocampus | Neufeld et al., 2011 | ||
| BDNF | Reduced BDNF expression | BALB/c (m) | Cortex, hippocampus | Sudo et al., 2004 | ||
| NGFI-A | Decreased Ngfi-a expression | NMRI (m) | Amygdala hippocampus, prefrontal cortex, striatum | Heijtz et al., 2011 | ||
| Stress hormone signalling | ACTH | Increased ACTH after 1 hour of restraint stress | BALB/c (m) | Blood: plasma | Yes | Sudo et al., 2004 |
| Corticosterone | Increased corticosterone after 30 minutes of stress | Swiss Webster (m, f) | Blood: plasma | Clarke et al., 2013 | ||
| Corticosterone | Increased corticosterone after open field stress | F344 rat (m) | Blood: serum | Crumeyrolle-Arias et al., 2014 | ||
| Corticosterone | Increased basal corticosterone | Swiss Webster (f) | Blood: plasma | Neufeld et al., 2011 | ||
| Corticosterone | Increased corticosterone after 1 hour of restraint stress | BALB/c (m) | Blood: plasma | Yes | Sudo et al., 2004 | |
| Glucocorticoid receptor | Decreased glucocorticoid mRNA expression | BALB/c (m) | Cortex | Sudo et al., 2004 |
Abbreviations: ACTH, adrenocorticotropic hormone; BDNF, brain-derived neurotrophic factor; EAE, experimental autoimmune encephalomyelitis; NGFI-A, nerve growth factor-inducible clone; PSD-95, post-synaptic density protein 95.
Summary of the molecular and cellular profile of GF mice. Experiments which are reversible or irreversible with bacterial colonization are indicated with ‘Yes’ or ‘No,’ respectively.