Neonatal handling and the expression of immunoreactivity to tyrosine hydroxylase in the hypothalamus of adult male rats

Abstract

Neonatal handling has long-lasting effects on behavior and stress reactivity. The purpose of the present study was to investigate the effect of neonatal handling on the number of dopaminergic neurons in the hypothalamic nuclei of adult male rats as part of a series of studies that could explain the long-lasting effects of neonatal stimulation. Two groups of Wistar rats were studied: nonhandled (pups were left undisturbed, control) and handled (pups were handled for 1 min once a day during the first 10 days of life). At 75-80 days, the males were anesthetized and the brains were processed for immunohistochemistry. An anti-tyrosine hydroxylase antibody and the avidin-biotinperoxidase method were used. Tyrosine hydroxylase-immunoreactive (TH-IR) neurons were counted bilaterally in the arcuate, paraventricular and periventricular nuclei of the hypothalamus in 30-µm sections at 120-µm intervals. Neonatal handling did not change the number of TH-IR neurons in the arcuate (1021 ± 206, N = 6; 1020 ± 150, N = 6; nonhandled and handled, respectively), paraventricular (584 ± 85, N = 8; 682 ± 62, N = 9) or periventricular (743 ± 118, N = 7; 990 ± 158, N = 7) nuclei of the hypothalamus. The absence of an effect on the number of dopaminergic cells in the hypothalamus indicates that the reduction in the amount of neurons induced by neonatal handling, as shown by other studies, is not a general phenomenon in the brain. Environmental stimuli during the neonatal period have lasting effects on emotional behavior and reactivity to stress in adult animals (1,2). Neonatal handling has been used as an experimental model to examine the mechanisms by which early environmental changes could affect neural systems, leading to stable behavioral and neuroendocrine changes (3-6). This apparently harmless procedure in infancy reduces fear in novel environments (5-7) and the secretion of corticosterone, adrenocorticotrophin and prolactin in response to stressors in adulthood (4-6). Furthermore, preliminary results from our laboratory showed that neonatal manipulation reduced the number of neurons in the medial amygdala, the prefrontal cortex (8) and the locus coeruleus (9), and decreased the number of somatostatinergic neurons in the hypothalamic periventricular nucleus

Precocious hippocampal structural and functional changes in gestational protein-restricted male elderly offspring: an Alzheimer-simile disease model?

“…CC-BY 4.0 International license made available under a (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is The copyright holder for this preprint this version posted April 7, 2021. ; https://doi.org/10.1101/2021.04.07.438796 doi: bioRxiv preprint Besides, consistent with previous studies, LP offspring significantly reduced lifespan (approximately 12 weeks) compared to NP offspring [79][80][81]. Incidentally, studies investigating the relationship among influence at the beginning of the developmental phase, fetal programming, and shortening of telomeres found each of these were strongly associated with perinatal stressors such as maternal stress, maternal food restriction, and maternal overnutrition [69-72].…”

“…We suggest that these neural disorders may be key in causing the cognitive decline in early-stage AD-like rodent models. Besides, consistent with previous studies, LP offspring significantly reduced lifespan (approximately 12 weeks) compared to NP offspring [79][80][81]. Incidentally, studies investigating the relationship among influence at the beginning of the developmental phase, fetal programming, and shortening of telomeres found each of these were strongly associated with perinatal stressors such as maternal stress, maternal food restriction, and maternal overnutrition [69][70][71][72].…”

Gestational protein restriction induces CA3 dendritic atrophy in dorsal hippocampal neurons but does not alter learning and memory performance in adult offspring

“…Although the underlying mechanisms are still unclear, the association between maternal undernutrition and hormonal dysfunction has been proposed to induce intrauterine fetal programming. Studies have demonstrated that gestational protein restriction leads to severe physiological and morphological changes in neurons (Huang et al, 2003; Hoffmann and Schmitt, 2004; Hermel et al, 2001; Feoli et al, 2006; de Lima et al, 2012), in addition to behavioral changes (de Oliveira, 1985; Riul et al, 1999) and delays in cognitive and intellectual functions (Barnes, 1976; Wainwright and Colombo, 2006). During normal pregnancy, the fetus is protected from the high maternal glucocorticoid (GC) levels by placental 11‐βHSD2, which efficiently inactivates corticosterone to 11‐dehydrocorticosterone in rodents.…”

Effects of early life stress on biochemical indicators of the dopaminergic system: a 3 level meta-analysis of rodent studies

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