#INTERGENERATIONAL TRAUMA TRANSMISSION PLUS#

p Percentage of freezing behavior in contextual fear conditioning assay ( n = 10 c → C, 10 s → S). o Time mice spent to make a decision in T-maze spontaneous assay ( n = 10 c → C, 10 s → S). n Percentage of the alternation choice mice made in the T-maze spontaneous assay ( n = 10 c → C, 10 s → S). j Discrimination index in the social interaction assay ( n = 9 c → C, 9 s → S). i Time mice spent interacting with empty cup and unfamiliar mouse in the social interaction assay ( n = 9 c → C, 9 s → S).

#INTERGENERATIONAL TRAUMA TRANSMISSION PLUS#

g, h Elevated plus maze measure of percent entry to ( h) Closed (unpaired t-test t = 0.05, P = 0.95), and ( g) open arms (unpaired t-test t = 0.74, P = 0.46). e, f Elevated plus maze measure of time spent in ( f) Closed (unpaired t-test t = 0.788, P = 0.44), and ( e) open arms (unpaired t-test t = 0.788, P = 0.44). Two-way ANOVA revealed a significant zone effect ( F 1,36 = 1453, P 0.05). d Time mice spent in the central and peripheral zones in 10 min in the locomotion assay ( n = 10 c → C, 10 s → S). b Time-course of the locomotor activity, ( c) Distance mice travelled in 60 min of the locomotion assay ( n = 10 c → C, 10 s → S). b, c s → S pups display normal locomotor activity.

Most strikingly, early pharmacological interventions with acetyl-L-carnitine (ALCAR) supplementation produced long-lasting protection against intergenerational trauma-induced depression.Ī Schematic of the experiment design. Bioinformatic analyses revealed stress- and hypoxia-response metabolic pathways in the neonates, which produced long-lasting alterations in mitochondrial energy metabolism and epigenetic processes (DNA and chromatin modifications). Striking increases in the mitochondrial hypoxia marker and epigenetic modifier 2-hydroxyglutaric acid in the brains of neonates and adults exposed prenatally to trauma indicated mitochondrial dysfunction and epigenetic mechanisms. The behavioral deficits were associated with profound changes in the brain metabotranscriptome. Good caregiving by normal mothers did not reverse prenatal trauma-induced behaviors, indicating a two-hit stress mechanism comprising both in-utero abnormalities and early-life poor parenting. Normal pups raised by traumatized mothers exhibited similar behavioral deficits to those induced in pups raised by their biological traumatized mothers. Here, we demonstrate that trauma exposure during pregnancy induces in mouse offspring social deficits and depressive-like behavior. Whether intergenerational trauma transmission is a consequence of in-utero neurodevelopmental disruptions versus early-life mother-infant interaction is unknown. Intergenerational trauma increases lifetime susceptibility to depression and other psychiatric disorders.

Intergenerational trauma transmission