Publications by authors named "Iwona Majcher-Maślanka"

10 Publications

  • Page 1 of 1

A Search for Biomarkers of Early-life Stress-related Psychopathology: Focus on 70-kDa Heat Shock Proteins.

Neuroscience 2021 Mar 2. Epub 2021 Mar 2.

Maj Institute of Pharmacology, Polish Academy of Sciences, Department of Pharmacology, Laboratory of Pharmacology and Brain Biostructure, Smętna Street 12, 31-343 Kraków, Poland. Electronic address:

Clinical studies clearly indicate that early-life stress (ELS) may cause physical and mental health problems later in life. Therefore, the identification of universal biomarkers of ELS-related diseases is very important. The 70-kDa heat shock proteins (HSP70s), specifically HSPA5 and HSPA1B, have been recently shown to be potentially associated with occurrence of anxiety, mood disorders, and schizophrenia; thus, we hypothesized that HSP70s are potential candidate biomarkers of ELS-induced psychopathologies. A maternal separation (MS) procedure in rats was used to model ELS, and the expression of HSPA5 and HSPA1B was investigated in the blood, medial prefrontal cortex (mPFC), and hippocampus of juvenile, preadolescent, and adult animals. We also studied the effects of MS on the long-term potentiation (LTP) and behavioral phenotypes of adult rats. We found that MS enhanced the expression of HSPA1B mRNA in the blood and mPFC of juvenile and preadolescent rats. This increase was accompanied by an increase in the HSPA1A/1B protein levels in the mPFC and hippocampus of juvenile rats that persisted in the mPFC until adulthood. MS juvenile and adult rats showed enhanced HSPA5 mRNA expression in the blood and increased HSPA5 protein expression in the mPFC (juveniles) and hippocampus (adults). Concurrently, MS adult rats exhibited aberrations in LTP in the mPFC and hippocampus and a less anxious behavioral phenotype. These results indicate that MS may produce enduring overexpression of HSPA1B and HSPA5 in the brain and blood. Therefore, both HSP70 family members may be potential candidate peripheral and brain biomarkers of ELS-induced changes in brain functioning.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuroscience.2021.02.026DOI Listing
March 2021

1MeTIQ and olanzapine, despite their neurochemical impact, did not ameliorate performance in fear conditioning and social interaction tests in an MK-801 rat model of schizophrenia.

Pharmacol Rep 2021 Apr 6;73(2):490-505. Epub 2021 Jan 6.

Department of Neurochemistry, Maj Institute of Pharmacology, Polish Academy of Sciences, Cracow, Poland.

Background: The aim of the present study was to evaluate the effect of 1MeTIQ on fear memory and social interaction in an MK-801-induced model of schizophrenia. The results obtained after administration of 1MeTIQ were compared with those obtained with olanzapine, an antipsychotic drug.

Methods: Sprague-Dawley rats received a single injection of MK-801 to induce behavioral disorders. 1MeTIQ was given either acutely in a single dose or chronically for 7 consecutive days. Olanzapine was administered once. In groups receiving combined treatments, 1MeTIQ or olanzapine was administered 20 min before MK-801 injection. Contextual fear conditioning was used to assess disturbances in fear memory (FM), and the sociability of the rats was measured in the social interaction test (SIT). Biochemical analysis was carried out to evaluate monoamine levels in selected brain structures after treatment.

Results: Our results are focused mainly on data obtained from neurochemical studies, demonstrating that 1MeTIQ inhibited the MK-801-induced reduction in dopamine levels in the frontal cortex and increased the 5-HT concentration. The behavioral tests revealed that acute administration of MK-801 caused disturbances in both the FM and SIT tests, while neither 1MeTIQ nor olanzapine reversed these deficits.

Conclusion: 1MeTIQ, although pharmacologically effective (i.e., it reverses MK-801-induced changes in monoamine activity), did not influence MK-801-induced social and cognitive deficits. Thus, our FM tests and SIT did not support the main pharmacological hypotheses that focus on dopamine system stabilization and dopamine-serotonin system interactions as probable mechanisms for inhibiting the negative symptoms of schizophrenia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s43440-020-00209-9DOI Listing
April 2021

Maternal separation disturbs postnatal development of the medial prefrontal cortex and affects the number of neurons and glial cells in adolescent rats.

Neuroscience 2019 12 6;423:131-147. Epub 2019 Nov 6.

Maj Institute of Pharmacology, Polish Academy of Sciences, Department of Pharmacology, Laboratory of Pharmacology and Brain Biostructure, 31-343 Kraków, Smętna Street 12, Poland. Electronic address:

Adolescence is a period of extensive brain maturation. In particular, the regions of the medial prefrontal cortex (mPFC) undergo intense structural and functional refinement during adolescence. Disturbances in mPFC maturation have been implicated in the emergence of multiple psychopathologies during adolescence. One of the essential risk factors for the development of mental illness in adolescence is early-life stress (ELS), which may interfere with brain maturation. However, knowledge of the mechanisms by which ELS affects mPFC maturation and functioning in adolescents is very limited. In the present study, we applied a maternal separation (MS) procedure in rats to model ELS and studied its effect on the number of neurons and glial cells in the prelimbic region of the mPFC (PLC) of adolescent rats. Moreover, the expression of markers of cell proliferation and apoptosis was also studied. We found that MS rats had more neurons, astrocytes, and NG2-glial cells in the PLC. In contrast, the number of microglial cells was reduced in MS rats. These changes were accompanied by the decreased expression of proapoptotic genes and the increased expression of some prosurvival genes. Concurrently, MS did not affect cell proliferation in adolescents. Moreover, MS induced anxiety-like behaviors, but not anhedonic-like behavior, in adolescents. These results suggest that ELS may disturb neurodevelopmental apoptosis of neurons and early-postnatal proliferation and/or apoptosis of different populations of glial cells in the PLC. ELS-induced aberrations in the postnatal maturation of the PLC may affect cortical network organization and functioning and determine vulnerability to psychopathologies in adolescents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuroscience.2019.10.033DOI Listing
December 2019

The impact of early-life stress on corticosteroid carrier protein levels and 11β-hydroxysteroid dehydrogenase 1 expression in adolescent rats.

Pharmacol Rep 2019 Apr 28;71(2):347-350. Epub 2018 Nov 28.

Institute of Pharmacology, Polish Academy of Sciences, Laboratory of Pharmacology and Brain Biostructure, Kraków, Poland. Electronic address:

Background: Corticosteroid-binding globulin (CBG), albumin and 11β-hydroxysteroid dehydrogenase (11β-HSD) enzymes play crucial roles in the bioavailability of glucocorticoids. Downstream of the adrenal glands, these proteins affect glucocorticoid levels in target tissues. Early-life stress (ELS) is known to program glucocorticoid action at many levels. The effects of ELS on the concentrations and synthesis of CBG and albumin and on the expression of 11β-HSD remain unclear.

Methods: The maternal separation (MS) procedure in rats on postnatal days 1-14 was used as a model of ELS. On postnatal day 35 (adolescence), the serum corticosterone, CBG and albumin concentrations of male rats were measured by ELISA, while the mRNA and protein levels of CBG, albumin and 11β-HSD1 in the liver and brain were examined by RT-qPCR and Western blot, respectively.

Results: Under basal conditions, MS rats displayed lower levels of serum CBG and albumin. However, MS did not affect CBG or albumin synthesis in the liver, suggesting that the half-life and/or secretion of these proteins were influenced by MS. Additionally, MS rats showed increased protein expression of 11β-HSD1, specifically in the medial prefrontal cortex.

Conclusions: These results indicate that ELS may potentially program glucocorticoid action through its effects on glucocorticoid bioavailability in tissues.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pharep.2018.11.003DOI Listing
April 2019

Previous Early-life Stress Modifies Acute Corticosterone-induced Synaptic Plasticity in the Medial Prefrontal Cortex of Adolescent Rats.

Neuroscience 2018 05 31;379:316-333. Epub 2018 Mar 31.

Institute of Pharmacology, Polish Academy of Sciences, Laboratory of Pharmacology and Brain Biostructure, 31-343 Kraków, Smętna street 12, Poland. Electronic address:

Stress can either strengthen coping strategies or enhance the risk of depression and anxiety. Synaptic plasticity is one of the key brain functions that can be affected by stress. We have previously shown that early-life stress in the form of maternal separation (MS) impairs functional synaptic plasticity in the medial prefrontal cortex (mPFC), i.e., long-term potentiation (LTP), in adolescent rats. It has been postulated that a previous experience of prolonged stress can modify the response to a subsequent acute stress challenge and influence coping strategies. Therefore, in the present study, we examined how previous MS experience influenced acute stress-induced changes in the LTP and expression of genes and proteins engaged in synaptic plasticity in the mPFC of adolescent rats. To mimic acute stress, we applied acute injections of corticosterone (CORT) and its vehicle (VEH). In control rats, acute CORT injection enhanced LTP in the mPFC. In contrast, MS rats generally exhibited an impairment of LTP that was not further affected by CORT. Moreover, for many studied parameters, such as induction of cFos and Arc mRNA and protein and activation of BDNF, GDNF and NCAM mRNA, MS rats showed diminished, vague or absent responses to acute VEH/CORT compared with those of control rats. These results suggest that previous early-life stress experiences may induce adaptive plasticity within the mPFC, which influences the response to acute stress challenge and coping strategies in adolescents. Depending on the specific environmental context, this phenomenon may lead to either future vulnerability or future resilience to stress-related psychopathologies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuroscience.2018.03.038DOI Listing
May 2018

The effects of early-life stress on dopamine system function in adolescent female rats.

Int J Dev Neurosci 2017 Apr 5;57:24-33. Epub 2017 Jan 5.

Institute of Pharmacology, Polish Academy of Sciences, Laboratory of Pharmacology and Brain Biostructure, 31-343 Kraków, Smętna Street 12, Poland. Electronic address:

During adolescence, many neural systems, including the dopamine system, undergo essential remodeling and maturation. It is well known that early-life stress (ELS) increases the risk for many psychopathologies during adolescence and adulthood. It is hypothesized that ELS interferes with the maturation of the dopamine system. There is a sex bias in the prevalence of stress-related mental disorders. Information regarding the effects of ELS on brain functioning in females is very limited. In the current study, maternal separation (MS) procedures were carried out to study the effects of ELS on dopamine system functioning in adolescent female rats. Our study showed that MS increased the density of tyrosine hydroxylase immunoreactive fibers in the prelimbic cortex (PLC) and nucleus accumbens (Acb). These changes were accompanied by a decrease in the level of D5 receptor mRNA and an increase in D2 receptor mRNA expression in the PLC of MS females. Conversely, D1 and D5 receptor mRNA levels were augmented in the caudate putamen (CPu), while the expression of the D3 dopamine receptor transcript was reduced in MS females. Additionally, in the Acb, MS elicited a decrease in D2 receptor mRNA expression. At the behavioral level, MS increased apomorphine-induced locomotion; however, it did not change locomotor responses to selective D1/D5 receptor agonist and attenuated D2/D3 receptor agonist-triggered locomotion. Moreover, MS decreased D1/D5 receptor agonist-induced grooming behavior. These results indicate that ELS disrupts dopamine receptor function in the PLC and basal ganglia during adolescence in females and may predispose them to psychopathologies during adolescence and adulthood.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijdevneu.2017.01.001DOI Listing
April 2017

Early-life stress increases the survival of midbrain neurons during postnatal development and enhances reward-related and anxiolytic-like behaviors in a sex-dependent fashion.

Int J Dev Neurosci 2015 Aug 14;44:33-47. Epub 2015 May 14.

Laboratory of Pharmacology and Brain Biostructure, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343 Kraków, Poland.

Clinical studies have suggested that early-life stress (ELS) increases the risk of psychopathologies that are strongly associated with dysfunction of dopaminergic neurotransmission. Thus, ELS may interfere with the development and maturation of the dopaminergic system; however, the mechanisms involved in such interference are poorly understood. In the present study, we investigated the effect of ELS on the survival of specific populations of neurons in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) during postnatal development. First, we injected bromodeoxyuridine (BrdU) into pregnant rat dams on embryonic days 12, 13 and 14 to permanently label midbrain neurons. Then, after birth, the dams and litters were subjected to a maternal separation (MS) procedure to model ELS conditions. The number of BrdU+ neurons and the total number of neurons (cresyl violet+, CV+) were estimated in both male and female juvenile, adolescent, and adult rats. Moreover, sucrose preference and anxiety-like behaviors were studied during adulthood. We found that MS permanently increased the number of BrdU+ and CV+ neurons in the VTA of males. In the SNc, a temporary increase in the number of BrdU+ neurons was observed in juvenile MS males; however, only adult MS males displayed an increase in the number of CV+ neurons. Immunofluorescence analysis implied that MS affected the fate of non-dopaminergic neurons. MS males displayed anxiolytic-like behavior and an increase in sucrose preference. These results suggest that ELS induces distinct dysregulation in the midbrain circuitry of males, which may lead to sex-specific psychopathology of the reward system.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijdevneu.2015.05.002DOI Listing
August 2015

Impact of early-life stress on the medial prefrontal cortex functions - a search for the pathomechanisms of anxiety and mood disorders.

Pharmacol Rep 2013 ;65(6):1462-70

Laboratory of Pharmacology and Brain Biostructure, Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland.

Although anxiety and mood disorders (MDs) are the most common mental diseases, the etiologies and mechanisms of these psychopathologies are still a matter of debate. The medial prefrontal cortex (mPFC) is a brain structure that is strongly implicated in the pathophysiology of these disorders. A growing number of epidemiological and clinical studies show that early-life stress (ELS) during the critical period of brain development may increase the risk for anxiety and MDs. Neuroimaging analyses in humans and numerous reports from animal models clearly demonstrate that ELS affects behaviors that are dependent on the mPFC, as well as neuronal activity and synaptic plasticity within the mPFC. The mechanisms engaged in ELS-induced changes in mPFC function involve alterations in the developmental trajectory of the mPFC and may be responsible for the emergence of both early-onset (during childhood and adolescence) and adulthood-onset anxiety and MDs. ELS-evoked changes in mPFC synaptic plasticity may constitute an example of metaplasticity. ELS may program brain functions by affecting glucocorticoid levels. On the molecular level, ELS-induced programming is registered by epigenetic mechanisms, such as changes in DNA methylation pattern, histone acetylation and microRNA expression. Vulnerability and resilience to ELS-related anxiety and MDs depend on the interaction between individual genetic predispositions, early-life experiences and later-life environment. In conclusion, ELS may constitute a significant etiological factor for anxiety and MDs, whereas animal models of ELS are helpful tools for understanding the pathomechanisms of these disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/s1734-1140(13)71506-8DOI Listing
October 2014

The effects of early-life adversity on fear memories in adolescent rats and their persistence into adulthood.

Behav Brain Res 2014 May 4;264:161-72. Epub 2014 Feb 4.

Laboratory of Pharmacology and Brain Biostructure, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Krakow, Poland.

Adolescence is a developmental period characterized by extensive morphological and functional remodeling of the brain. The processes of brain maturation during this period may unmask malfunctions that originate earlier in life as a consequence of early-life stress (ELS). This is associated with the emergence of many psychopathologies during adolescence, particularly affective spectrum disorders. In the present study, we applied a maternal separation (MS) procedure (3h/day, on postnatal days 1-14) as a model of ELS to examine its effects on the acquisition, expression and extinction of fear memories in adolescent rats. Additionally, we studied the persistence of these memories into adulthood. We found that MS decreased the expression of both contextual (CFC) and auditory (AFC) fear conditioning in adolescent rats. Besides, MS had no impact on the acquisition of extinction learning. During the recall of extinction MS animals both, those previously subjected and not subjected to the extinction session, exhibited equally low levels of freezing. In adulthood, the MS animals (conditioned during adolescence) still displayed impairments in the expression of AFC (only in males) and CFC. Furthermore, the MS procedure had also an impact on the expression of CFC (but not AFC) after retraining in adulthood. Our findings imply that ELS may permanently affect fear learning and memory. The results also support the hypothesis that, depending on individual predispositions and further experiences, ELS may either lead to a resilience or a vulnerability to early- and late-onsets psychopathologies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbr.2014.01.040DOI Listing
May 2014

Early-life stress affects the structural and functional plasticity of the medial prefrontal cortex in adolescent rats.

Eur J Neurosci 2013 Jul 15;38(1):2089-107. Epub 2013 Apr 15.

Laboratory of Pharmacology and Brain Biostructure, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland.

Early life experiences are crucial factors that shape brain development and function due to their ability to induce structural and functional plasticity. Among these experiences, early-life stress (ELS) is known to interfere with brain development and maturation, increasing the risk of future psychopathologies, including depression, anxiety, and personality disorders. Moreover, ELS may contribute to the emergence of these psychopathologies during adolescence. In this present study, we investigated the effects of ELS, in the form of maternal separation (MS), on the structural and functional plasticity of the medial prefrontal cortex (mPFC) and anxiety-like behavior in adolescent male rats. We found that the MS procedure resulted in disturbances in mother-pup interactions that lasted until weaning and were most strongly demonstrated by increases in nursing behavior. Moreover, MS caused atrophy of the basal dendritic tree and reduced spine density on both the apical and basal dendrites in layer II/III pyramidal neurons of the mPFC. The structural changes were accompanied by an impairment of long-term potentiation processes and increased expression of key proteins, specifically glutamate receptor 1, glutamate receptor 2, postsynaptic density protein 95, αCa(2+) /calmodulin-dependent protein kinase II and αCa(2+)/calmodulin-dependent protein kinase II phosphorylated at residue Thr305, that are engaged in long-term potentiation induction and maintenance in the mPFC. We also found that the MS animals were more anxious in the light/dark exploration test. The results of this study indicate that ELS has a significant impact on the structural and functional plasticity of the mPFC in adolescents. ELS-induced adaptive plasticity may underlie the pathomechanisms of some early-onset psychopathologies observed in adolescents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ejn.12208DOI Listing
July 2013