Abstract
As an adverse form of early-life stress (ELS), maternal separation (MS) can interfere with the development of cognition and behaviors of adolescent rodents. Brain-derived neurotrophic factor (BDNF) is involved in the regulation of brain development and function, but the molecular mechanisms by which BDNF regulates brain function and behavior in MS with different stressor strengths remain unclear. This descriptive study characterized the levels of BDNF in the prefrontal cortex (PFC) and plasma corticosterone (CORT) from the offspring of rats exposed to early handling (EH, 15-min separation per day) and prolonged MS (PMS, 180-min separation per day), during postnatal days (PND) 1‑21. The behavioral and biochemical analyses were performed during adolescence (PND 42‑56). PMS resulted in reduced weight and decreased locomotor activity in the open field test and Y-maze task compared to control (CON) group, with EH showing an intermediate phenotype. BDNF protein levels in the PFC were lower in PMS compared to EH and further reduced in CON male rats. Plasma CORT levels were higher in PMS compared to CON with EH again showing intermediate levels. Neither PMS or EH affected spatial learning in the Y-maze task. These findings indicate that longer periods of maternal separation are necessary to increase anxiety-like behavior, elevate CORT levels, and further suppress BDNF levels in the PFC, providing a possible mechanism to explain why more severe forms of ELS lead to more significant psychiatric and medical consequences later in life.
Highlights
Early-life stress (ELS) is a broad term used to describe various forms of stress experienced in early life, including physical, sexual, and emotional forms of abuse and neglect suffered by developing children [1], which can alter the normal pattern of brain development, resulting in various short- and long-term dysfunctions in cognitive, emotional, and other behavioral processes [2]
analysis of variance (ANOVA) results showed that age [F(7, 24)= 831.588, p= 0.000] and prolonged MS (PMS) [F(14, 50)= 4.714, p= 0.000] had a significant effect on the body weight of rats, and there was an interaction between the two treatment factors
The aim of the present study was to examine the consequences of two models of early-life stress (ELS) that differ in terms of their severity on anxiety-like behavior and spatial memory as well as the Brain-derived neurotrophic factor (BDNF) levels in the prefrontal cortex (PFC) and plasma CORT levels
Summary
Early-life stress (ELS) is a broad term used to describe various forms of stress experienced in early life, including physical, sexual, and emotional forms of abuse and neglect suffered by developing children [1], which can alter the normal pattern of brain development, resulting in various short- and long-term dysfunctions in cognitive, emotional, and other behavioral processes [2]. It is thought that early disruptions of social interaction in young children may affect brain development and have long-term neurochemical, endocrine, and behavioral effects [3]. It has been reported that MS can improve reverse learning in adolescent rats [8]. These seemingly conflicting results may reflect experimental differences in the MS procedure, the developmental age at which the testing was performed, or the cognitive test used [11]
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