Publications by authors named "Nadja Freund"

Studying behavioural lateralization in animals holds great potential for answering important questions in laterality research and clinical neuroscience. However, comparative research encounters challenges in reliability and validity, requiring new approaches and innovative designs to overcome. Although validated tests exist for some species, there is yet no standard test to compare lateralized manual behaviours between individuals, populations, and animal species.

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Mood disorders, including depressive and bipolar disorders, are the group of psychiatric disorders with the highest prevalence and disease burden. However, their pathophysiology remains poorly understood. Animal models are an extremely useful tool for the investigation of molecular mechanisms underlying these disorders.

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Article Synopsis
  • The early postnatal period is crucial for brain development, and stress during this time can lead to neurobiological changes and increased risk for anxiety and depression later in life.
  • The study used maternal separation (MS) in rats to mimic early life stress and found that it led to increased anxiety behavior in different tests during adolescence and adulthood, with no significant sex differences observed.
  • Additionally, MS was linked to changes in the number of parvalbumin-positive interneurons in the amygdala, suggesting that early stress has lasting effects on brain structure and behavior, which may evolve as the animal matures.
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In patients with bipolar disorder, we do not only see a cycling of mood episodes, but also a shift in circadian rhythm. In the present overview, the circadian rhythm, the "internal clock", and their disruptions are briefly described. In addition, influences on circadian rhythms such as sleep, genetics, and environment are discussed.

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In this overview, influences of microglia activation and disturbances of the microbiome in the devastating disorder schizophrenia are discussed. Despite previous assumptions of a primary neurodegenerative character of this disorder, current research underlines the important autoimmunological and inflammatory processes here. Early disturbances of microglial cells as well as cytokines could lead to weakness of the immunological system in the prodromal phase and then fully manifest in patients with schizophrenia.

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Background: Numerous cortical and subcortical structures have been studied extensively concerning alterations of their integrity as well as their neurotransmitters in depression. However, connections between these structures have received considerably less attention.

Objective: This systematic review presents results from recent neuroimaging as well as neuropathologic studies conducted on humans and other mammals.

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Article Synopsis
  • The postpartum period is a critical time for women, with about 10%-15% at risk for postpartum depression (PPD), making it important to explore its causes and effects.
  • This review examines the maternal separation (MS) model in rodents as a potential tool to better understand the challenges faced by mothers suffering from PPD.
  • Findings show that MS alters various aspects of maternal behavior, hormone levels, and gene expression in rodents, aligning with symptoms seen in PPD, suggesting that this model could enhance our understanding of PPD in humans.
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The prefrontal dopamine D1 receptor (D1R) is involved in cognitive processes. Viral overexpression of this receptor in rats further increases the reward-related behaviors and even its termination induces anhedonia and helplessness. In this study, we investigated the risky decision-making during D1R overexpression and its termination.

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Article Synopsis
  • - Atypical asymmetries in behavior have been linked to schizophrenia, with higher symptom severity potentially tied to weaker lateralization; this study explored how maternal immune activation (MIA) affects these asymmetries in offspring.
  • - MIA was induced in pregnant rats, leading to tests of their offspring's turning behavior, which showed significant differences: adolescents exhibited a rightward turning bias, while adults displayed no bias, suggesting reduced asymmetry over time.
  • - Analysis of dopamine D2 receptor (DRD2) mRNA expression indicated lower levels in adolescents exposed to MIA compared to controls, reinforcing the relationship between atypical asymmetries and schizophrenia, although further research is necessary to clarify these links.
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Recent 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.

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Mice and rats are among the most common animal model species in both basic and clinical neuroscience. Despite their ubiquity as model species, many clinically relevant brain-behaviour relationships in rodents are not well understood. In particular, data on hemispheric asymmetries, an important organizational principle in the vertebrate brain, are conflicting as existing studies are often statistically underpowered due to small sample sizes.

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Background Immunopathological concepts have been intensively discussed for schizophrenia. The polyriboinosinic-polyribocytidylic (PolyI:C) mouse model has been well validated to invasively study this disease. The intestinal microbiome exhibits broad immunological and neuronal activities.

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Perineuronal nets (PNNs) are specialized, reticular structures of the extracellular matrix (ECM) that can be found covering the soma and proximal dendrites of a neuronal subpopulation. Recent studies have shown that PNNs can highly influence synaptic plasticity and are disrupted in different neuropsychiatric disorders like schizophrenia. Interestingly, there is a growing evidence that microglia can promote the loss of PNNs and contribute to neuropsychiatric disorders.

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Background: Prefrontal dopamine D1 receptor (D1R) mediates behavior related to anxiety, reward and memory, and is involved in inflammatory processes, all of which are affected in bipolar disorder. Interleukin-6 (IL-6), a pro-inflammatory cytokine, is increased in patients with bipolar disorder in plasma samples, imaging studies and postmortem tissue and is an indicator for an inflammatory state. We could previously show that lentiviral overexpression of D1R in the medial prefrontal cortex (mPFC) of male adult rats and its termination induces bipolar disorder-like behavior.

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Background: Alterations in the hippocampus and prefrontal cortex (PFC) have frequently been reported in depressed patients. These parameters might prove to be a consistent finding in depression. In addition, peripheral DNA methylation of the MORC1 gene promoter showed stable associations with depression across independent samples.

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The time after parturition is a sensitive period for mothers where they are prone to develop psychopathological symptoms. Studies investigating dams after separation from their pups (maternal separation, MS) showed that MS induces alterations similar to postpartum depression. This study aims to give further details on affected behavior and neurobiology of dams after MS.

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Activation of the maternal immune system (MIA) during gestation is linked to neuropsychiatric diseases like schizophrenia. While many studies address behavioural aspects, less is known about underlying cellular mechanisms. In the following study, BALB/c mice received intraperitoneal injections of polyinosinic-polycytidylic acid (Poly I:C) (20 µg/ml) or saline (0.

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Atypical leftward behavioral asymmetries have been associated with early life stress and psychopathologies in humans and animals. Maternal separation (MS) is a frequently used model to investigate early life stress and psychopathologies but has not yet been studied in terms of asymmetries. This study aims to investigate whether prolonged MS induces atypical leftward asymmetries in the turning behavior of rats.

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In the central nervous system, activated microglia and astrocytes produce proinflammatory mediators such as inducible nitric oxide (iNOS) and cytokines. Uncontrolled release of these mediators induced by immune challenge can lead to increased vulnerability to complex brain disorders such as schizophrenia. In this study, BALB/c mice were injected intraperitoneally (i.

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Early detection markers for substance use disorders are urgently needed. Recently, an association between the methylation of Ganglioside-induced differentiation-associated protein 1 (GDAP1) and alcohol addiction was found in a US and German population. In this study, we investigate whether GDAP1 expression might be affected by cigarette smoke as well and thus might be a marker of substance addiction in general.

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Even though lithium is widely used as treatment for mood disorders, the exact mechanisms of lithium in the brain remain unknown. A potential mechanism affects the downstream target of the Wnt/β-catenin signaling pathway, specifically glutamine synthetase (GS). Here, we investigate the effect of lithium on GS-promoter activity in the brain.

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Background: Microinjections, lesions, viral-mediated gene transfer, or designer receptors exclusively activated by designer drugs (DREADDs) can identify brain signaling pathways and their pharmacology in research animals. Genetically modified animals are used for more precise assessment of neural circuits. However, only a few of the gene-based pathway modifications are available for use in outbred rat strains.

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Characterized by the switch of manic and depressive phases, bipolar disorder was described as early as the fifth century BC. Nevertheless up to date, the underlying neurobiology is still largely unclear, assuming a multifactor genesis with both biological-genetic and psychosocial factors. Significant process has been achieved in recent years in researching the causes of bipolar disorder with modern molecular biological (e.

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Rationale: Both methylphenidate (MPH), a catecholamine reuptake blocker, and guanfacine, an alpha2A agonist, are used to treat attention-deficit hyperactivity disorder (ADHD). Childhood impulsivity, including delay discounting, is associated with increased substance use during adolescence. These effects can be mitigated by juvenile exposure to MPH, but less is known about the long-term effects of developmental exposure to guanfacine in males and females.

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