Table 2.
Summary of brain structural and functional alterations induced by SI in rodents.
| Animal models | Age of SI | Onset of SI; SI period | Structural and functional changes | Ref |
|---|---|---|---|---|
| Mouse | Postnatal | Birth; 2 w | Increased level of myelin-related genes and depleted OPC pool | [112] |
| P10; 1.5/8 h | Activated Agrp neurons modulating ultrasonic vocalization | [95] | ||
| P14; 7d + 12 w | Activated astrocytes in the locus coeruleus | [113] | ||
| Juvenile | P21; 2 or 8 w | Reduced myelination and NRG-1–ErbB signaling | [32, 116] | |
| P21; 2 w | Increased firing property of FSPC interneurons and reduced excitatory synaptic inputs and intrinsic excitability in PH neurons in mPFC | [28, 29, 96] | ||
| P21; 2 w | Reduced excitability of parvalbumin interneurons in dmPFC and impaired active social approach | [97] | ||
| P21; 2 w | Reduced excitability of mPFC–pPVT neurons and social deficits | [35] | ||
| P21; 4 w | Reduced serotonergic fiber density in the inferior colliculus | [106] | ||
| P21; 5 w | Sex-specific behavioral abnormalities and altered neuronal activity in PFC, BLA, and VTA | [90] | ||
| P21; 8 w | Decreased excitability of mPFC IL–NAcSh neurons and impaired social recognition | [36] | ||
| P28; 1 w | Activated putative dopamine neurons in VTA which can be regulated by PVN oxytocin neurons | [89] | ||
| Adult | P35; 4 w | Abnormal connections with the dorsolateral orbitofrontal cortex | [88] | |
| 2 m; 4 w | Decreased number and overactivation of microglia | [115] | ||
| 2 m; 10–12 w | Anxiety-like symptoms and decreased CREB activity in NAcSh | [33] | ||
| 2–4 m; 2 w | Brain-wide upregulation of the neuropeptide Tac2/NkB | [34] | ||
| 3 m; 4 w | Accelerated necroptosis in BLA and behavioral inflexibility | [101] | ||
| Rat | Postnatal | Birth; 7 d | Elevated expression of neural proteins such as BDNF and reduced apoptosis and neuronal pruning | [108] |
| P2; 18 d | Reduced synaptogenesis and mature spine density in Hipp | [100] | ||
| P7-P11; 6 h/d | Inactivated cofilin and decreased AMPA receptors and LTP | [30, 98] | ||
| P14; 7 d | Fewer hippocampal microglia | [114] | ||
| Juvenile | P20; 26 d | Changed expression patterns of IEGs regulating cell differentiation and apoptosis in mPFC | [110] | |
| P21; 3 w | Enhanced LTP of NMDAR-mediated glutamatergic transmission | [31] | ||
| P21; 15 w | Decreased volume of Hipp and dentate gyrus; decreased activity of the Wnt–beta-catenin pathway in PFC | [85, 86] | ||
| P21; 8 w | Decreased dendritic spine density on pyramidal neurons in PFC and Hipp | [105] | ||
| P25–28; 30 d | Altered microtubule stability by decreased MAP-2 in Hipp | [104] | ||
| P28; 8 w | Reduced mPFC volume | [87] | ||
| Adult | 2 m; 7 d | Social memory deficit | [84] | |
| 3 m; 21 d | Increased mitochondrial glucocorticoid receptor in PFC and Hipp | [107] | ||
| Adult; 12 d | Delayed positive influence of running on adult neurogenesis in Hipp | [99] |
m month(s), w week(s), d day(s), Agrp Agouti-related peptide, AMPA amino-3-hydroxy-5-methylisoxazole-4-propionic acid, BDNF brain derived neurotrophic factor, BLA basolateral amygdala, CREB cAMP response element-binding protein, dmPFC dorsal medial prefrontal cortex, Hipp hippocampus, IEGs immediate early genes, IL infralimbic, LTP long-term potentiation, NAcSh nucleus accumbens shell, NMDAR N-methyl-D-aspartate receptor, NRG-1–ErbB neuregulin-1–Erb-b2 receptor tyrosine kinase 2, OPC oligodendrocyte progenitor cell, pPVT posterior paraventricular thalamus, PVN paraventricular nucleus, Tac2/NkB tachykinin 2/neurokinin B, VTA ventral tegmental area.