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Biomedical subjects

F A Henn

Publications and source records attributed to F A Henn.

At least 19 recordsLinked to original sources
PubMed2006

Altered NMDA receptor expression and behavior following postnatal hypoxia: potential relevance to schizophrenia.

The present study investigated the effects of chronic, repeated hypoxia during a postnatal vulnerable period. Acoustic startle response in adult rats was measured along with NMDA receptor binding and mRNA expression of subunits at postnatal days (PND) 11 and 120. Rats at PND 120 exhibited a deficit in prepulse inhibition of acoustic startle response. In PND 11 rats, chronic hypoxia decreased NMDA receptor binding and increased transcript expression of NR1 subunit in frontal and temporal regions, nucleus accumbens and hippocampus, while NR2A subunit expression was downregulated in hippocampal subregions. At PND 120, gene expression of NR1 was still increased in hippocampal, frontal and temporal subregions as well as nucleus accumbens. A prepulse inhibition deficit points to schizophrenia-like behavior in adult (PND 120) rats. Compensatory upregulation of NR1 expression may occur due to NMDA receptor hypofunction. We discuss this animal model to further analyze effects of hypoxia as a factor of obstetric complications in the pathophysiology of schizophrenia.

Animals↗
PubMed2006

ECT anesthesia: the lighter the better?

BACKGROUND: Electroconvulsive therapy (ECT) is a most effective treatment for patients with major affective disorders. The influence of anesthetic drugs on seizure "adequacy" or on treatment success has not been systematically investigated. METHODS: A bispectral EEG index score (BIS) was used to identify the depth of anesthesia during ECT. Our study included 22 major depressive episode (MDE) patients expanding to 219 ECTs (05/05-01/06) with no limitations of concurrent medication. RESULTS: Fourteen out of the 22 patients showed full remission. Individual number of ECT sessions needed to reach full remission correlated negatively with mean pre-ECT BIS values (p=0.001). Additionally, using a repeated measurement regression analysis significant correlations were found for pre-ECT BIS versus motor response time, seizure concordance, ictal coherence and peak heart rate. CONCLUSION: The results of our study suggest BIS-levels as a predictor of faster ECT response. Controlling BIS-levels before stimulation may have an additional effect on treatment success.

Aged↗
PubMed2005

[Treating depressive disorders with continuation electroconvulsive therapy].

Nowadays, electroconvulsive therapy (ECT) is undergoing a renaissance in psychiatry: it is now considered a first-line therapy for treating psychotic depression or other disorders with severe depressive symptoms. Surprisingly, ECT is most commonly not used as continuation therapy after acute remission. With rare exceptions, antidepressive medication is chosen for this purpose. The use of continuation ECT (cECT) and subsequent maintenance ECT (mECT) is not or just marginally mentioned in practice guidelines. In this article, we suggest guidelines for cECT, taking therapy recommendations and recent studies into account. Particularly, indication, management, comedication and comorbidity, side effects, and costs are examined. Today, cECT is underindicated as a result of assumed problems, fears, and stigmas. We would therefore recommend broader use of this proven treatment tool for keeping major depression in remission.

Depressive Disorder↗
PubMed2005

[One decade of functional imaging in schizophrenia research. From visualisation of basic information processing steps to molecular-genetic oriented imaging].

Modern neuroimaging techniques such as magnetic resonance imaging (MRI) and positron emission tomography (PET) have contributed tremendously to our current understanding of psychiatric disorders in the context of functional, biochemical and microstructural alterations of the brain. Since the mid-nineties, functional MRI has provided major insights into the neurobiological correlates of signs and symptoms in schizophrenia. The current paper reviews important fMRI studies of the past decade in the domains of motor, visual, auditory, attentional and working memory function. Special emphasis is given to new methodological approaches, such as the visualisation of medication effects and the functional characterisation of risk genes.

Biomarkers↗
PubMed2005

Reduced sensitivity to sucrose in rats bred for helplessness: a study using the matching law.

Anhedonia is a core symptom of depression. As it cannot be directly assessed in rodents, anhedonia is usually inferred from a reduced consumption of, or preference for, a reinforcer. In the present study we tried to improve the measurement of anhedonia by performing a detailed preference analysis based on the generalized matching law and tested its sensitivity in rats congenitally prone (cLH) or resistant (cNLH) to learned helplessness. According to the current interpretation of learned helplessness as a model for depression, a reduction in the rewarding properties of sucrose in cLH rats was hypothesized. Our results revealed that the 'preference allocation' index provided by this test, but not the traditional measures of sucrose consumption or preference over water, was significantly lower in cLH rats, and was correlated with the helpless behaviour as measured in an escape procedure. Therefore, it is clear that more subtle preference measures provided by the analysis of choice using the matching law principles are more sensitive and discriminative than those based on consumption of, or preference for, a single concentration of sucrose over water. Moreover, our data are in agreement with the proposed relationship between helplessness and sucrose preference, and support the usefulness of the cLH and cNLH rats as a model of depression.

Animals↗
PubMed2004

Differential expression of glutamate transporters EAAT1 and EAAT2 in mice deficient for PACAP-type I receptor.

Pituitary adenylate cyclase-activating polypeptide (PACAP) modulates glutamatergic neurotransmission and induces the expression of glutamate transporters EAAT1 and EAAT2 in newborn mouse astroglial cell cultures. Since nanomolar concentrations of PACAP exert this effect, signal transduction via the high affinity PACAP-type I-receptor PAC1 was assumed. To test this hypothesis and to assess the importance of PAC1-signalling in vivo, we analyzed glutamate transporter expression in mice with a PAC1 knockout. EAAT1 and EAAT2 expression was investigated in the hippocampus and the cerebral cortex of PAC1 mutant mice and wildtype littermates by semiquantitative in-situ-hybridization. PAC1-knockout mice show a subtle but significant reduction of EAAT1 expression in the dentate gyrus. In contrast, reduced expression levels of EAAT1 in the cerebral cortex did not reach statistical significance and EAAT2 expression was unchanged in CA3 and cerebral cortex of PAC1 mutant mice. Our data confirm the previously reported in-vitro-regulation of EAAT1 in the adult nervous system in vivo. EAAT2 expression, however, is unchanged in PAC1 knockout mice, most likely due to counterbalancing factors.

Amino Acid Transport System X-AG↗
PubMed2004

[Effect of antipsychotics on glutaminergic neural transmission in the animal model].

Post-mortem investigations have confirmed that glutamatergic NMDA, AMPA, and kainate receptors are involved in the pathophysiology of schizophrenia. It is still unclear, however, whether the altered number of receptors is caused by the disease itself or the medication. Therefore, animal models were investigated for effects of antipsychotic medication after treatment periods of up to 6 months, the results of which are summarized here. Generally, NMDA receptor binding was found to be increased in striatum and nucleus accumbens after therapy with haloperidol, whereas clozapine only increased the number of receptors in nucleus accumbens. While haloperidol led to an increase in AMPA receptors in the posterior cingulate gyrus, striatum, insular cortex, and n. accumbens, clozapine was found to elevate ligand binding in the anterior cingulate gyrus and infralimbic cortex. Although kainate receptor binding was increased in hippocampus by both antipsychotics, clozapine was significantly more effective. In conclusion, data reveal different effects from the typical neuroleptic haloperidol and the atypical antipsychotic clozapine. The results suggest that post-mortem findings in patients with schizophrenia may at least partially be explained by drug effects and plasticity changes induced by long-term medication with antipsychotics.

Animals↗
PubMed2004

Differential regulation of synaptic vesicle proteins by antidepressant drugs.

Synaptic vesicle proteins (SVP) play a critical role in neurotransmitter release and neural plasticity, and have been implicated in the pathophysiology of psychiatric disorders such as depression. Antidepressant drugs not only alter the level of neurotransmitters, but also modulate de novo gene transcription and synthesis of proteins involved in neural plasticity. In order to investigate the effects of antidepressant compounds on SVP-mRNA levels, the expressions of synaptophysin, synaptotagmin, VAMP, and synapsin-I were analysed by in situ hybridization in rats which had been treated with desipramine, fluoxetine, tranylcypromine, or saline. The results demonstrate that chronic treatment with fluoxetine and tranylcypromine leads to an increased expression of synaptophysin, but decreased expression of synaptotagmin and VAMP in the hippocampus and cerebral cortex. Additionally, synapsin I-mRNA levels in the hippocampus and cerebral cortex are significantly reduced in tranylcypromine-treated animals. This identifies SVP genes as target genes of antidepressant treatment.

Animals↗
PubMed2004

Differential effects of long-term treatment with clozapine or haloperidol on GABA transporter expression.

BACKGROUND: Post-mortem studies with brain samples of schizophrenic patients led revealed altered GABA-ergic markers like reduced expression of the GABA transporter GAT-1. Whether this effect is due to the pathophysiology of schizophrenia or to antipsychotic treatment has not been investigated. We therefore established an animal trial of long-term antipsychotic treatment to address this question. METHODS: A total of 33 adult male rats were investigated in three cohorts of 11 animals. One group received clozapine (45 mg/kg/ day), another group haloperidol (1.5 mg/kg/day), and the third one pH-adapted water over a period of 6 months. In situ hybridization with cRNA probes specific for GABA transporters VGAT, GAT-1 and GAT-3 were performed in comparison to control animals. RESULTS: While GAT-1 was upregulated, VGAT expression declined in cortical and limbic brain regions, whereby haloperidol showed a greater effect than clozapine. GAT-3 expression was suppressed in parietal and temporal cortex. CONCLUSIONS: We thus conclude that long-term antipsychotic treatment alters GABA transporter expression in rat. The upregulation of GAT-1 contrasts with the post-mortem finding of reduced GAT-1 expression in schizophrenic patients. Our results facilitate the distinction between disease dependent changes of GABAergic markers and medication effects.

Amino Acid Transport Systems↗
PubMed2004

Basic pathophysiological mechanisms in depression: what are they and how might they affect the course of the illness?

Basic pathophysiological mechanisms in affective disorders are discussed. Studies carried out suggest that changes in neurogenesis do not underlie the behavioral changes which lead to helplessness. Since the behavioral changes leading to depressive or anxious behaviors are not correlated with changes in neurogenesis it appears unlikely that a decrease in the rate of neurogenesis is the basis for depression. A modified gene expression resulting in both functional and structural brain changes remains the most consistent hypothesis to explain how affective disorders may occur. An alternative candidate, synaptogenesis, appears as a likely candidate and requires further experimental testing.

Brain↗
PubMed2003

Hippocampal volume and cell proliferation after acute and chronic clozapine or haloperidol treatment.

The dentate gyrus contains progenitor cells possessing the capacity to proliferate until and throughout adulthood. There is little information about the influence of antipsychotics on cell proliferation. To address this, we investigated the influence of acute and chronic haloperidol and clozapine treatment on the total number of newly dividing cells and hippocampal volume using an animal model with doses equivalent to the therapeutic range in humans. Rats were treated with either acute or 28 days haloperidol (1 mg/kg i.p. or 1,5 mg/kg/day oral) or clozapine (30 mg/kg i.p. or 45 mg/kg/day oral). After BrdU injection, immunohistochemistry was performed in serial hippocampal brain sections. Total BrdU-labeled cell number and hippocampus volume were estimated using stereological methods. Neither neuroleptic altered total number of newly dividing cells in the dentate gyrus. In contrast, chronic haloperidol treatment did increase total hippocampal volume suggesting that haloperidol alters neuroplastic processes or glial morphology rather than cell proliferation.

Animals↗
PubMed2003

Signal enhancement through heteronuclear polarisation transfer in in-vivo 31P MR spectroscopy of the human brain.

Significant (31)P NMR signal enhancement through heteronuclear polarisation transfer was obtained in model solutions and in vivo on a 1.5-T whole-body MR scanner equipped with two RF channels. The much higher population differences involved in proton Zeeman energy levels can be transferred to the (31)P levels with the refocused INEPT (insensitive nucleus enhancement by polarisation transfer) double-resonance experiment by means of a series of simultaneously applied broadband RF pulses. INEPT achieves a polarisation transfer from (1)H to (31)P spin states by directly reordering the populations in spin systems with heteronuclear scalar coupling. Thus, only the (31)P NMR signal of metabolites with scalar (1)H-(31)P coupling is amplified, while the other metabolite signals in the spectra are suppressed. Compared to Ernst-angle excitation, a repetition-time-dependent signal enhancement of eta=(29+/-3)% for methylene diphosphonic acid (MDPA) and eta=(56+/-1)% for phosphorylethanolamine (PE) was obtained on model solutions through optimisation of the temporal parameters of the pulse experiment. The results are in good agreement with numerical calculations of the theoretical model for the studied spin systems. With optimised echo times, in-vivo (31)P signal enhancement of the same order was obtained in studies of the human brain.

Brain↗
PubMed2003

Effects of chronic haloperidol and clozapine treatment on AMPA and kainate receptor binding in rat brain.

BACKGROUND: Alterations in AMPA and kainate receptor binding have been revealed in post-mortem schizophrenic brains. As most patients had been treated with antipsychotics, medication effects cannot be excluded as a possible explanation for these results. METHODS: Within the framework of this animal study, we investigated [3H]AMPA and [3H]kainate receptor binding in different rat brain regions following 6 months of oral treatment with either haloperidol (1.5 mg/kg/day) or clozapine (45 mg/kg/day). RESULTS: AMPA receptor binding was increased after haloperidol treatment in the striatum, nucleus accumbens, cingulate cortex, and insular cortex. Clozapine showed increased AMPA receptor binding only in the anterior cingulate cortex. Kainate receptor binding was increased by both drugs in all hippocampal subfields. CONCLUSIONS: This altered receptor binding may be related to beneficial neuroleptic effects and side effects. Furthermore, neuroleptic therapy may contribute to some of the post-mortem findings in the striatum in schizophrenia.

Animals↗
PubMed2002

A fully automated method for tissue segmentation and CSF-correction of proton MRSI metabolites corroborates abnormal hippocampal NAA in schizophrenia.

In this report, we describe the implementation and application of a fully automated segmentation routine using SPM99 algorithms and MATLAB for clinical Magnetic Resonance Spectroscopic Imaging (MRSI) studies. By segmenting high-resolution 3-D image data and coregistering the results to the spatial localizer slices of a spectroscopy examination, the program offers the possibility to easily calculate segmentation maps for a large variety of MRSI experiments. The segmented data are corrected for the individual point-spread function, slice and VOI profiles for measurement sequences with selective pulses as well as for the chemical shifts of different metabolites. The new method was applied to investigate discrete hippocampal metabolite abnormalities in a small sample of schizophrenic patients in comparison to healthy controls (15 patients, 15 controls). Only after correction was the N-acetyl-aspartate (NAA) signal significantly lower in patients compared to controls. No differences were found for the corrected signals from the creatine/phosphocreatine (Cr) or choline-containing compounds (Ch). These results are in good agreement with neuropathological and previous MR spectroscopy studies of the hippocampus in schizophrenic patients.

Adult↗
PubMed2002

[Molecular aspects of antidepressive therapy. Transsynaptic effects on signal transduction, gene expression and neuronal plasticity].

Simple neurotransmitter theories cannot sufficiently explain the mode of action of antidepressant drugs. Molecular pharmacological studies demonstrate that antidepressive treatment initially modulates the neurotransmitter-receptor interaction, subsequently influences signal transduction cascades beyond the synapse and gene transcription mechanisms, and ultimately triggers the expression of specific target genes. Such genes often code for molecules which play an important role in the maintenance of neural and synaptic plasticity. Chronic (but not acute) treatment with antidepressants modulates, for example, the cAMP-second-messenger system and increases the expression of neurotrophic factors. Furthermore, antidepressants promote hippocampal neurogenesis. Stress, an important risk factor for psychiatric disorders, often induces opposite effects. A better understanding of the molecular and cellular effects of stress and therapy with psychotropic drugs will stimulate the development of innovative treatment strategies for which an optimised antidepressant efficacy with a simultaneously improved tolerance is expected.

Antidepressive Agents↗