Morc1 as a potential new target gene in mood regulation: when and where to find in the brain

AbstractRecent animal and human studies connected the Morc family CW-type zinc finger 1 (Morc1) gene with early life stress and depression. Moreover, the Morc superfamily is related to epigenetic regulation in diverse nuclear processes. So far, the Morc1 gene was mainly studied in spermatogenesis, whereas its distribution and function in the brain are still unknown. In a first attempt to characterize Morc1 in the brain, we performed a Western Blot analysis as well as a real-time PCR analysis during different stages of development. Additionally, we detected Morc1 mRNA using real-time PCR in different mood-regulating brain areas in adult rats. We found that MORC1 protein as well as Morc1 mRNA is already expressed in the brain at embryonic day 14 and is stably expressed until adulthood. Furthermore, Morc1 mRNA is present in many important brain areas of mood regulation like the medial prefrontal cortex, the nucleus accumbens, the hippocampus, the hypothalamus, and the amygdala. The ample distribution in the brain and its molecular structure as a zinc finger protein indicate that Morc1 might act as a transcription factor. This function and its expression in mood-regulating areas already in the early brain development turn Morc1 into a possible candidate gene for mediating early life stress and depression.

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Long-term effects of early life stress on the brain monoamines level in the rats

Neurophysiologie Clinique ◽

10.1016/j.neucli.2012.11.035 ◽

2013 ◽

Vol 43 (1) ◽

pp. 79

Author(s):

R. Ghalamghash ◽

H.Z. Mammedov ◽

H. Ashayeri ◽

A. Hosseini

Keyword(s):

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Long Term Effects ◽

Brain Monoamines ◽

The Brain

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Abstract 17: Early Life Stress Sensitizes The Angiotensin II-elicited Hypertensive Response

Hypertension ◽

10.1161/hyp.76.suppl_1.17 ◽

2020 ◽

Vol 76 (Suppl_1) ◽

Author(s):

Baojian Xue ◽

Terry Beltz ◽

Fang Guo ◽

David M Pollock ◽

Jennifer S Pollock ◽

...

Keyword(s):

Mrna Expression ◽

Proinflammatory Cytokines ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Male Rats ◽

Sprague Dawley ◽

Cns Inflammation ◽

Wide Range ◽

The Brain

Separation of neonatal rodent pups from their mothers has been used as a model to study the effects of early life stress (ELS) on behavioral and physiological responses in adults. Using an Induction-Delay-Expression experimental paradigm, our previous studies demonstrate that a wide range of stressors administered during an induction period produces hypertensive response sensitization (HTRS) in response to a subsequent pro-hypertensive stimulus. HTRS is accompanied by activation of the brain renin-angiotensin system (RAS) and CNS inflammation. The present study investigated whether ELS induces HTRS and changes in brain-related underlying mechanisms. Rat neonates from Sprague-Dawley breeders were subjected to ELS by separating them each morning from their mothers for 3 h on postnatal days 2 to 14. Pups from non-handled litters formed control groups. At 10 weeks of age, male rats were used to evaluate blood pressure and autonomic function using telemetric probes and pharmacological methods. In addition, in separate control and ELS groups, the lamina terminalis (LT) structures and the hypothalamic paraventricular nucleus (PVN) were analyzed for mRNA expression of RAS components and proinflammatory cytokines. Adult ELS rats as compared to non-separated controls exhibited 1) HTRS during expression testing using 2 week ANG II infusions (120 ng/kg/min s.c.; ELS animals, Δ45.5±4.5 mmHg vs. controls, Δ22.4±3.1 mmHg); 2) a greater reduction in mean arterial pressure following ganglionic blockade (hexamethonium, 30 mg/kg, ip), 3) increased sympathetic drive to the heart (atenolol, 8 mg/kg, ip), 4) decreased vagal tone (atropine, 8 mg/kg, ip), and 5) increased mRNA expression of several components of the brain RAS and proinflammatory cytokines in the LT and PVN. These results suggest that maternal ELS may predispose individuals to hypertension that is mediated by upregulation of the brain RAS and proinflammatory cytokines and increased sympathetic drive to the cardiovascular system.

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Effects of Early-Life Stress on the Brain and Behaviors: Implications of Early Maternal Separation in Rodents

International Journal of Molecular Sciences ◽

10.3390/ijms21197212 ◽

2020 ◽

Vol 21 (19) ◽

pp. 7212

Author(s):

Mayumi Nishi

Keyword(s):

Child Abuse ◽

Hpa Axis ◽

Brain Function ◽

Life Stress ◽

Early Life ◽

Maternal Separation ◽

Early Life Stress ◽

Emotional Behavior ◽

Neural Basis ◽

The Brain

Early-life stress during the prenatal and postnatal periods affects the formation of neural networks that influence brain function throughout life. Previous studies have indicated that maternal separation (MS), a typical rodent model equivalent to early-life stress and, more specifically, to child abuse and/or neglect in humans, can modulate the hypothalamic–pituitary–adrenal (HPA) axis, affecting subsequent neuronal function and emotional behavior. However, the neural basis of the long-lasting effects of early-life stress on brain function has not been clarified. In the present review, we describe the alterations in the HPA-axis activity—focusing on serum corticosterone (CORT)—and in the end products of the HPA axis as well as on the CORT receptor in rodents. We then introduce the brain regions activated during various patterns of MS, including repeated MS and single exposure to MS at various stages before weaning, via an investigation of c-Fos expression, which is a biological marker of neuronal activity. Furthermore, we discuss the alterations in behavior and gene expression in the brains of adult mice exposed to MS. Finally, we ask whether MS repeats itself and whether intergenerational transmission of child abuse and neglect is possible.

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S.01.02 The interplay between early-life stress and neuroinflammation on structure and function of the brain throughout life

European Neuropsychopharmacology ◽

10.1016/j.euroneuro.2018.11.915 ◽

2019 ◽

Vol 29 ◽

pp. S4-S5

Author(s):

A. Korosi

Keyword(s):

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Structure And Function ◽

And Function ◽

The Brain

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Lasting Differential Effects on Plasticity Induced by Prenatal Stress in Dorsal and Ventral Hippocampus

Neural Plasticity ◽

10.1155/2016/2540462 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10 ◽

Cited By ~ 17

Author(s):

Gayane Grigoryan ◽

Menahem Segal

Keyword(s):

Prenatal Stress ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Brain Structures ◽

Traumatic Experience ◽

Stressful Stimulation ◽

The Brain ◽

Two Sectors ◽

Structure And Functions

Early life adversaries have a profound impact on the developing brain structure and functions that persist long after the original traumatic experience has vanished. One of the extensively studied brain structures in relation to early life stress has been the hippocampus because of its unique association with cognitive processes of the brain. While the entire hippocampus shares the same intrinsic organization, it assumes different functions in its dorsal and ventral sectors (DH and VH, resp.), based on different connectivity with other brain structures. In the present review, we summarize the differences between DH and VH and discuss functional and structural effects of prenatal stress in the two sectors, with the realization that much is yet to be explored in understanding the opposite reactivity of the DH and VH to stressful stimulation.

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Traumatic Injury to the Developing Brain: Emerging Relationship to Early Life Stress

Frontiers in Neurology ◽

10.3389/fneur.2021.708800 ◽

2021 ◽

Vol 12 ◽

Author(s):

Kaila N. Parker ◽

Michael H. Donovan ◽

Kylee Smith ◽

Linda J. Noble-Haeusslein

Keyword(s):

Brain Injury ◽

Life Stress ◽

Early Life ◽

Brain Injuries ◽

Traumatic Injury ◽

Early Life Stress ◽

Early Age ◽

Functional Impairments ◽

The Brain

Despite the high incidence of brain injuries in children, we have yet to fully understand the unique vulnerability of a young brain to an injury and key determinants of long-term recovery. Here we consider how early life stress may influence recovery after an early age brain injury. Studies of early life stress alone reveal persistent structural and functional impairments at adulthood. We consider the interacting pathologies imposed by early life stress and subsequent brain injuries during early brain development as well as at adulthood. This review outlines how early life stress primes the immune cells of the brain and periphery to elicit a heightened response to injury. While the focus of this review is on early age traumatic brain injuries, there is also a consideration of preclinical models of neonatal hypoxia and stroke, as each further speaks to the vulnerability of the brain and reinforces those characteristics that are common across each of these injuries. Lastly, we identify a common mechanistic trend; namely, early life stress worsens outcomes independent of its temporal proximity to a brain injury.

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The Effects of Early Life Stress on the Brain and Behaviour: Insights From Zebrafish Models

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.657591 ◽

2021 ◽

Vol 9 ◽

Author(s):

Helen Eachus ◽

Min-Kyeung Choi ◽

Soojin Ryu

Keyword(s):

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Brain Regions ◽

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

Current Status ◽

Comprehensive Overview ◽

Behavioural Changes ◽

The Brain

The early life period represents a window of increased vulnerability to stress, during which exposure can lead to long-lasting effects on brain structure and function. This stress-induced developmental programming may contribute to the behavioural changes observed in mental illness. In recent decades, rodent studies have significantly advanced our understanding of how early life stress (ELS) affects brain development and behaviour. These studies reveal that ELS has long-term consequences on the brain such as impairment of adult hippocampal neurogenesis, altering learning and memory. Despite such advances, several key questions remain inadequately answered, including a comprehensive overview of brain regions and molecular pathways that are altered by ELS and how ELS-induced molecular changes ultimately lead to behavioural changes in adulthood. The zebrafish represents a novel ELS model, with the potential to contribute to answering some of these questions. The zebrafish offers some important advantages such as the ability to non-invasively modulate stress hormone levels in a whole animal and to visualise whole brain activity in freely behaving animals. This review discusses the current status of the zebrafish ELS field and its potential as a new ELS model.

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