Anita C Hansson

Publications (48) View all

• Article: Neurocircuitry for modeling drug effects.

  Hamid R Noori, Rainer Spanagel, Anita C Hansson
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  ABSTRACT: The identification and functional understanding of the neurocircuitry that mediates alcohol and drug effects that are relevant for the development of addictive behavior is a fundamental challenge in addiction research. Here we introduce an assumption-free construction of a neurocircuitry that mediates acute and chronic drug effects on neurotransmitter dynamics that is solely based on rodent neuroanatomy. Two types of data were considered for constructing the neurocircuitry: (1) information on the cytoarchitecture and neurochemical connectivity of each brain region of interest obtained from different neuroanatomical techniques; (2) information on the functional relevance of each region of interest with respect to alcohol and drug effects. We used mathematical data mining and hierarchical clustering methods to achieve the highest standards in the preprocessing of these data. Using this approach, a dynamical network of high molecular and spatial resolution containing 19 brain regions and seven neurotransmitter systems was obtained. Further graph theoretical analysis suggests that the neurocircuitry is connected and cannot be separated into further components. Our analysis also reveals the existence of a principal core subcircuit comprised of nine brain regions: the prefrontal cortex, insular cortex, nucleus accumbens, hypothalamus, amygdala, thalamus, substantia nigra, ventral tegmental area and raphe nuclei. Finally, by means of algebraic criteria for synchronizability of the neurocircuitry, the suitability for in silico modeling of acute and chronic drug effects is indicated. Indeed, we introduced as an example a dynamical system for modeling the effects of acute ethanol administration in rats and obtained an increase in dopamine release in the nucleus accumbens-a hallmark of drug reinforcement-to an extent similar to that seen in numerous microdialysis studies. We conclude that the present neurocircuitry provides a structural and dynamical framework for large-scale mathematical models and will help to predict chronic drug effects on brain function.
  Addiction Biology 09/2012; 17(5):827-64. · 4.83 Impact Factor
• Article: Translational magnetic resonance spectroscopy reveals excessive central glutamate levels during alcohol withdrawal in humans and rats.

  Derik Hermann, Wolfgang Weber-Fahr, Alexander Sartorius, Mareen Hoerst, Ulrich Frischknecht, Nuran Tunc-Skarka, Stephanie Perreau-Lenz, Anita C Hansson, Bertram Krumm, Falk Kiefer, Rainer Spanagel, Karl Mann, Gabriele Ende, Wolfgang H Sommer
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  ABSTRACT: In alcoholism, excessive glutamatergic neurotransmission has long been implicated in the acute withdrawal syndrome and as a key signal for dependence-related neuroplasticity. Our understanding of this pathophysiological mechanism originates largely from animal studies, but human data are needed for translation into successful medication development. We measured brain glutamate levels during detoxification in alcohol-dependent patients (n = 47) and in healthy control subjects (n = 57) as well as in a rat model of alcoholism by state-of-the-art ¹H-magnetic magnetic resonance spectroscopy at 3 and 9.4 T, respectively. We found significantly increased glutamate levels during acute alcohol withdrawal in corresponding prefrontocortical regions of treatment-seeking alcoholic patients and alcohol-dependent rats versus respective control subjects. The augmented spectroscopic glutamate signal is likely related to increased glutamatergic neurotransmission because, enabled by the high field strength of the animal scanner, we detected a profoundly elevated glutamate/glutamine ratio in alcohol-dependent rats during acute withdrawal. All dependence-induced metabolic alterations normalize within a few weeks of abstinence in both humans and rats. Our data provide first-time direct support from humans for the glutamate hypothesis of alcoholism, demonstrate the comparability of human and animal magnetic resonance spectroscopy responses, and identify the glutamate/glutamine ratio as potential biomarker for monitoring disease progression.
  Biological psychiatry 09/2011; 71(11):1015-21. · 8.93 Impact Factor
• Article: Dissociation of antidepressant-like activity of escitalopram and nortriptyline on behaviour and hippocampal BDNF expression in female rats.

  Anita C Hansson, Roberto Rimondini, Markus Heilig, Aleksander A Mathé, Wolfgang H Sommer
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  ABSTRACT: A major hypothesis of depression postulates that a dysregulation of the neurotrophin systems is directly involved in the pathophysiology of depression, and that restoration of such deficits may underlie the therapeutic efficacy of antidepressant treatment. One key finding supporting this hypothesis is upregulation of brain derived neurotrophic factor (BDNF) in the hippocampus after antidepressant treatment. Here, we further test the hypothesis of BDNF involvement in antidepressant action in a genetic rat model of depression after chronic oral treatment with escitalopram, nortriptyline or placebo. Active treatments had significant behavioural antidepressant-like actions in female rats of the Flinders Sensitive Line (FSL) and non-selected Sprague Dawley (SD) rats, while Flinders Resistant Line (FRL) rats were unaffected. Escitalopram, but not nortriptyline, markedly reduced BDNF mRNA levels in the dentate gyrus of FSL rats. The BDNF downregulation was common to the four major promoters of the gene. Treatments did not affect BDNF expression in FRL or SD strains. We conclude that the antidepressant effects of escitalopram and nortriptyline, two common drugs with different pharmacological profiles, appear to be unrelated to the regulation of hippocampal BDNF expression in female rats. These results indicate that the tropic hypothesis of depression has limitations and emphasize the need for validated disease models of depression to assess potential treatment targets.
  Journal of Psychopharmacology 01/2011; 25(10):1378-87. · 3.04 Impact Factor
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  Available from: Anita C Hansson

  Article: Increased mRNA Levels of TCF7L2 and MYC of the Wnt Pathway in Tg-ArcSwe Mice and Alzheimer's Disease Brain

  Elin S Blom, Wang Yijing, Skoglund Lena, Anita C Hansson, Ubaldi Massimo, Lourdusamy Anbarasu, Wolfgang H Sommer, Mielke Matthew, Bradley T Hyman, Heilig Markus, Lannfelt Lars, Lars N G Nilsson, Ingelsson Martin
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  ABSTRACT: Several components in the Wnt pathway, including β-catenin and glycogen synthase kinase 3 beta, have been implied in AD pathogenesis. Here, mRNA brain levels from five-month-old tg-ArcSwe and nontransgenic mice were compared using Affymetrix microarray analysis. With surprisingly small overall changes, Wnt signaling was the most affected pathway with altered expression of nine genes in tg-ArcSwe mice. When analyzing mRNA levels of these genes in human brain, transcription factor 7-like 2 (TCF7L2) and v-myc myelocytomatosis viral oncogene homolog (MYC), were increased in Alzheimer's disease (AD) (P < .05). Furthermore, no clear differences in TCF7L2 and MYC mRNA were found in brains with frontotemporal lobar degeneration, suggesting that altered regulation of these Wnt-related genes could be specific to AD. Finally, mRNA levels of three neurogenesis markers were analyzed. Increased mRNA levels of dihydropyrimidinase-like 3 were observed in AD brain, suggesting that altered Wnt pathway regulation may signify synaptic rearrangement or neurogenesis.
  International Journal of Alzheimer's Disease. 01/2011;
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  Available from: Anita C Hansson

  Article: Long-term suppression of forebrain neurogenesis and loss of neuronal progenitor cells following prolonged alcohol dependence in rats.

  Anita C Hansson, Kimberly Nixon, Roberto Rimondini, Ruslan Damadzic, Wolfgang H Sommer, Robert Eskay, Fulton T Crews, Markus Heilig
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  ABSTRACT: Alcohol dependence leads to persistent neuroadaptations, potentially related to structural plasticity. Previous work has shown that hippocampal neurogenesis is modulated by alcohol, but effects of chronic alcohol on neurogenesis in the forebrain subventricular zone (SVZ) have not been reported. Effects in this region may be relevant for the impairments in olfactory discrimination present in alcoholism. Here, we examined the effects of prolonged alcohol dependence on neurogenesis. Rats were sacrificed directly after 7 wk of intermittent alcohol vapour exposure, or 3, 7 or 21 d into abstinence. Proliferation was assessed using BrdU and Ki67 immunoreactivity, newly differentiated neurons (neurogenesis) as doublecortin-immunoreactivity (DCX-IR), and neural stem cells using the SOX2 marker. In the dentate gyrus, chronic dependence resulted in a pattern similar to that previously reported for acute alcohol exposure: proliferation and neurogenesis were suppressed by the end of exposure, rebounded on day 3 of abstinence, and returned to control levels by days 7 and 21. In the SVZ, proliferation was also suppressed at the end of alcohol exposure, followed by a proliferation burst 3 d into abstinence. However, in this area, there was a trend for reduced proliferation on days 7 and 21 of abstinence, and this was accompanied by significant suppression of DCX-IR, indicating a long-term suppression of forebrain neurogenesis. Finally, a decrease in the SOX2 stem cell marker was detected at days 7 and 21, suggesting long-term reduction of the SVZ stem cell pool. While suppression of hippocampal neurogenesis by alcohol dependence is transient, the suppression in the forebrain SVZ appears long-lasting.
  The International Journal of Neuropsychopharmacology 03/2010; 13(5):583-93. · 4.58 Impact Factor