Becoming Stressed: Does the Age Matter? Reviewing the Neurobiological and Socio-Affective Effects of Stress throughout the Lifespan

Mañas-Ojeda, Aroa; Ros-Bernal, Francisco; Olucha-Bordonau, Francisco E.; Castillo-Gómez, Esther

doi:10.3390/ijms21165819

Cited by 14 publications

(12 citation statements)

References 128 publications

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“…Unlike previous studies that did not find a correlation of Hb volume and age [ 21 , 22 ], this study showed that the older the individuals in the depressed group, the smaller the volume. The older the patients with MDD, the more likely they are to live in isolation, have less interpersonal contact, and have a higher likelihood of physical illness [ 53 ], which may lead to a smaller whole Hb volume. To our knowledge, there are no research results that clearly demonstrate a correlation between Hb volume and duration of education or antidepressant medication use.…”

Section: Discussionmentioning

confidence: 99%

Left-right asymmetric and smaller right habenula volume in major depressive disorder on high-resolution 7-T magnetic resonance imaging

Cho

Park

et al. 2021

PLoS ONE

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The habenula (Hb) has been hypothesized to play an essential role in major depressive disorder (MDD) as it is considered to be an important node between fronto-limbic areas and midbrain monoaminergic structures based on animal studies. In this study, we aimed to investigate the differences in volume and T1 value of the Hb between patients with MDD and healthy control (HC) subjects. Analysis for the Hb volumes was performed using high-resolution 7-T magnetic resonance (MR) image data from 33 MDD patients and 36 healthy subjects. Two researchers blinded to the clinical data manually delineated the habenular nuclei and Hb volume, and T1 values were calculated based on overlapping voxels. We compared the Hb volume and T1 value between the MDD and HC groups and compared the volume and T1 values between the left and right Hbs in each group. Compared to HC subjects, MDD patients had a smaller right Hb volume; however, there was no significant volume difference in the left Hb between groups. In the MDD group, the right Hb was smaller in volume and lower in T1 value than the left Hb. The present findings suggest a smaller right Hb volume and left-right asymmetry of Hb volume in MDD. Future high-resolution 7-T MR imaging studies with larger sample sizes will be needed to derive a more definitive conclusion.

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Section: Discussionmentioning

confidence: 99%

Left-right asymmetric and smaller right habenula volume in major depressive disorder on high-resolution 7-T magnetic resonance imaging

Cho

Park

et al. 2021

PLoS ONE

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“…The exposure to chronic stress can lead to an altered balance between excitatory and inhibitory neurotransmission ( Page and Coutellier, 2019 ) and constitutes a predisposing factor for the development of different psychiatric disorders ( McEwen, 2000 ). Interestingly, the brain response to chronic stress is also influenced by the age of the individuals and their sex ( Hodes and Epperson, 2019 ; Spear, 2000 ; Mañas-Ojeda et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Long term effects of peripubertal stress on excitatory and inhibitory circuits in the prefrontal cortex of male and female mice

Bueno-Fernández

Pérez-Rando

Alcaide

et al. 2021

Neurobiology of Stress

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The impact of stressful events is especially important during early life, because certain cortical regions, especially the prefrontal cortex (PFC), are still developing. Consequently, aversive experiences that occur during the peripubertal period can cause long-term alterations in neural connectivity, physiology and related behaviors. Although sex influences the stress response and women are more likely to develop stress-related psychiatric disorders, knowledge about the effects of stress on females is still limited. In order to analyze the long-term effects of peripubertal stress (PPS) on the excitatory and inhibitory circuitry of the adult PFC, and whether these effects are sex-dependent, we applied an unpredictable chronic PPS protocol based on psychogenic stressors. Using two strains of transgenic mice with specific fluorescent cell reporters, we studied male and diestrus females to know how PPS affects the structure and connectivity of parvalbumin expressing (PV+) interneurons and pyramidal neurons. We also studied the expression of molecules related to excitatory and inhibitory neurotransmission, as well as alterations in the expression of plasticity-related molecules. The structure of pyramidal neurons was differentially affected by PPS in male and female mice: while the former had a decreased dendritic spine density, the latter displayed an increase in this parameter. PPS affected the density of puncta expressing excitatory and inhibitory synaptic markers exclusively in the female mPFC. Similarly, only in female mice we observed an increased complexity of the dendritic tree of PV+ neurons. Regarding the perisomatic innervation on pyramidal and PV + neurons by basket cells, we found a significant increase in the density of puncta in stressed animals, with interesting differences between the sexes and the type of basket cell analyzed. Finally, the PPS protocol also altered the total number of somata expressing the polysialylated form of the neural cell adhesion molecule (PSA-NCAM) when we analyzed both sexes together. These results highlight the strong programming effects of aversive experiences during early life for the establishment of cortical circuitry and the special impact of these stressful events on females.

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“…Anxiety, along with associated disorders such as post-traumatic stress disorder (PTSD), have in recent years been strongly associated with premature aging conditions [150][151][152][153]. With respect to the impact of RXFP3 upon anxiety-related disorders, it has been shown that specific central stimulation generates an anxiolytic effect in model organisms [154]. While acute effects of RXFP3 stimulation can generate anxiolytic effects, it has recently been shown that chronic localized RXFP3 stimulation instead can actually promote anxiety behavior [26].…”

Section: Anxiety and Post-traumatic Stress Disordermentioning

confidence: 99%

The Relaxin-3 Receptor, RXFP3, Is a Modulator of Aging-Related Disease

Leysen

Walter

Clauwaert

et al. 2022

IJMS

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During the aging process our body becomes less well equipped to deal with cellular stress, resulting in an increase in unrepaired damage. This causes varying degrees of impaired functionality and an increased risk of mortality. One of the most effective anti-aging strategies involves interventions that combine simultaneous glucometabolic support with augmented DNA damage protection/repair. Thus, it seems prudent to develop therapeutic strategies that target this combinatorial approach. Studies have shown that the ADP-ribosylation factor (ARF) GTPase activating protein GIT2 (GIT2) acts as a keystone protein in the aging process. GIT2 can control both DNA repair and glucose metabolism. Through in vivo co-regulation analyses it was found that GIT2 forms a close coexpression-based relationship with the relaxin-3 receptor (RXFP3). Cellular RXFP3 expression is directly affected by DNA damage and oxidative stress. Overexpression or stimulation of this receptor, by its endogenous ligand relaxin 3 (RLN3), can regulate the DNA damage response and repair processes. Interestingly, RLN3 is an insulin-like peptide and has been shown to control multiple disease processes linked to aging mechanisms, e.g., anxiety, depression, memory dysfunction, appetite, and anti-apoptotic mechanisms. Here we discuss the molecular mechanisms underlying the various roles of RXFP3/RLN3 signaling in aging and age-related disorders.

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Becoming Stressed: Does the Age Matter? Reviewing the Neurobiological and Socio-Affective Effects of Stress throughout the Lifespan

Cited by 14 publications

References 128 publications

Left-right asymmetric and smaller right habenula volume in major depressive disorder on high-resolution 7-T magnetic resonance imaging

Left-right asymmetric and smaller right habenula volume in major depressive disorder on high-resolution 7-T magnetic resonance imaging

Long term effects of peripubertal stress on excitatory and inhibitory circuits in the prefrontal cortex of male and female mice

The Relaxin-3 Receptor, RXFP3, Is a Modulator of Aging-Related Disease

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