Isolation Stress During the Prepubertal Period in Rats Induces Long-Lasting Neurochemical Changes in the Prefrontal Cortex

Since emotional stress elicits brain activation, mitochondria should be a key component of stressed brain response. However, few studies have focused on mitochondria functioning in these conditions. In this work, we aimed to determine the effects of an acute restraint stress on rat brain mitochondrial functions, with a focus on permeability transition pore (PTP) functioning. Rats were divided into two groups, submitted or not to an acute 30-min restraint stress (Stress, S-group, vs. Control, C-group). Brain was removed immediately after stress. Mitochondrial respiration and enzymatic activities (complex I, complex II, hexokinase) were measured. Changes in PTP opening were assessed by the Ca 2+ retention capacity.Cell signaling pathways relevant to the coupling between mitochondria and cell function (adenosine monophosphateactivated protein kinase, phosphatidylinositol 3-kinase, glycogen synthase kinase 3 beta, MAPK, and cGMP/NO) were measured. The effect of glucocorticoids was also assessed in vitro. Stress delayed (43%) the opening of PTP and resulted in a mild inhibition of complex I respiratory chain. This inhibition was associated with significant stress-induced changes in adenosine monophosphate-activated protein kinase signaling pathway without changes in brain cGMP level. In contrast, glucocorticoids did not modify PTP opening. These data suggest a rapid adaptive mechanism of brain mitochondria in stressed conditions, with a special focus on PTP regulation.

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“…; Krolow et al . ; Kuchukashvili et al . ); so far, few studies have investigated this effect in acute stress conditions.…”

Section: Discussionmentioning

confidence: 97%

“…It has been reported that exposure to chronic stress situations induces activation in juvenile (Krolow et al . ) or inhibition of respiratory chain complex in adult (Rezin et al . ).…”

mentioning

confidence: 99%

Acute stress delays brain mitochondrial permeability transition pore opening

Batandier

Poulet

Hininger

et al. 2014

Journal of Neurochemistry

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“…It is important to note that this sensitive period of development requires higher energy, since the brain is in a constant process of organizing and of neural maturation. This is true especially for the prefrontal cortex, which has a characteristic late maturation and is sensitive to external factors such as diet and stress (Krolow et al, 2012; Sherman et al, 2014). The present study showed that the effects of stress alone were different in some responses when associated with a chronic HFD, indicating that different environmental interventions in high plasticity periods may program distinct outcomes in adulthood.…”

Section: Discussionmentioning

confidence: 99%

“…Alterations in BDNF have been associated with memory impairment induced by high fat diet intake (Cui et al, 2012; Granholm et al, 2008), or exposure to stressors early in life (Oomen et al, 2010; Wang et al, 2011). Also relevant to the development of central nervous system is the activity of Na + ,K + ‐ATPase, an enzyme that maintains the neurochemical gradient essential for neuronal excitability, and which activity is influenced by environmental interventions, like stress in early life (Noschang et al, 2012; Silveira et al, 2011) and palatable diet intake (Krolow et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Early life adversities or high fat diet intake reduce cognitive function and alter BDNF signaling in adult rats: Interplay of these factors changes these effects

Arcego

Krolow

Lampert

et al. 2016

Intl J of Devlp Neuroscience

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Environmental factors, like early exposure to stressors or high caloric diets, can alter the early programming of central nervous system, leading to long-term effects on cognitive function, increased vulnerability to cognitive decline and development of psychopathologies later in life. The interaction between these factors and their combined effects on brain structure and function are still not completely understood. In this study, we evaluated long-term effects of social isolation in the prepubertal period, with or without chronic high fat diet access, on memory and on neurochemical markers in the prefrontal cortex of rats. We observed that early social isolation led to impairment in short-term and working memory in adulthood, and to reductions of Na(+),K(+)-ATPase activity and the immunocontent of phospho-AKT, in prefrontal cortex. Chronic exposure to a high fat diet impaired short-term memory (object recognition), and decreased BDNF levels in that same brain area. Remarkably, the association of social isolation with chronic high fat diet rescued the memory impairment on the object recognition test, as well as the changes in BDNF levels, Na(+),K(+)-ATPase activity, MAPK, AKT and phospho-AKT to levels similar to the control-chow group. In summary, these findings showed that a brief social isolation period and access to a high fat diet during a sensitive developmental period might cause memory deficits in adulthood. On the other hand, the interplay between isolation and high fat diet access caused a different brain programming, preventing some of the effects observed when these factors are separately applied.

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“…IR-induced PPI deficits are associated with specific neurochemical and molecular changes in frontal cortex, including alterations in levels of dopamine (DA), immunologic and mitochondrial markers (Krolow et al 2012) [9], synaptic proteins and receptor levels (Hermes et al 2011) [10], expression of genes related to glutamate (Turnock-Jones et al 2009; Murphy et al 2010) [11,12] and GABA function (Murphy et al 2010) [12], and structure, the latter attributed to a loss of mPFC neuropil (Day-Wilson et al 2006) [8]. Such a long list of alterations in the mPFC suggests that the impact of IR on mPFC function is both pervasive and non-selective; it is not yet clear which of these changes – if any - are responsible for reduced PPI, a phenotype associated with neurodevelopmental brain disorders, including schizophrenia (Braff et al 1978; cf.…”

Section: Introductionmentioning

confidence: 99%

Forebrain gene expression predicts deficits in sensorimotor gating after isolation rearing in male rats

Swerdlow

Light

Trim

et al. 2013

Behavioural Brain Research

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Compared to socially housed (SH) rats, adult isolation-reared (IR) rats exhibit phenotypes relevant to schizophrenia (SZ), including reduced prepulse inhibition (PPI) of startle. PPI is normally regulated by the medial prefrontal cortex (mPFC) and nucleus accumbens (NAC). We assessed PPI, auditory-evoked local field potentials (LFPs) and expression of 7 PPI- and SZ-related genes in the mPFC and NAC, in IR and SH rats. Buffalo (BUF) rats were raised in same-sex groups of 2–3 (SH) or in isolation (IR). PPI was measured early (d53) and later in adulthood (d74); LFPs were measured approximately on d66. Brains were processed for RT-PCR measures of mPFC and NAC expression of Comt, Erbb4, Grid2, Ncam1, Slc1a2, Nrg1 and Reln. Male IR rats exhibited PPI deficits, most pronounced at d53; male and female IR rats had significantly elevated startle magnitude on both test days. Gene expression levels were not significantly altered by IR. PPI levels (d53) were positively correlated with mPFC expression of several genes, and negatively correlated with NAC expression of several genes, in male IR but not SH rats. Late (P90) LFP amplitudes correlated significantly with expression levels of 6/7 mPFC genes in male rats, independent of rearing. After IR that disrupts early adult PPI in male BUF rats, expression levels of PPI- and SZ-associated genes in the mPFC correlate positively with PPI, and levels in the NAC correlate negatively with PPI. These results support the model that specific gene-behavior relationships moderate the impact of early-life experience on SZ-linked behavioral and neurophysiological markers.

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Isolation Stress During the Prepubertal Period in Rats Induces Long-Lasting Neurochemical Changes in the Prefrontal Cortex

Cited by 19 publications

References 64 publications

Acute stress delays brain mitochondrial permeability transition pore opening

Acute stress delays brain mitochondrial permeability transition pore opening

Early life adversities or high fat diet intake reduce cognitive function and alter BDNF signaling in adult rats: Interplay of these factors changes these effects

Forebrain gene expression predicts deficits in sensorimotor gating after isolation rearing in male rats

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