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Christian Lange-Asschenfeldt

Publications and source records attributed to Christian Lange-Asschenfeldt.

9 recordsLinked to original sources
PubMed2006

Hippocampal synaptic depression following spatial learning in a complex maze.

Activity-dependent alteration in synaptic efficacy is referred to as synaptic plasticity and is the believed hallmark of any learning process. Here we employed a recently validated complex maze for spatial training and investigated the impact of repeated and extensive training on basal synaptic transmission of the hippocampal Schaffer collateral-CA1 synaptic connection in vitro. In the present experiments, male CD-1 mice were trained in a complex maze for eight consecutive days five times a day. Subsequently, input-output functions of field excitatory postsynaptic potentials (fEPSPs) recorded in the CA1 area following stimulation of the Schaffer collateral-commissural fiber pathway were analyzed in acute hippocampal slices. We found a marked right shift of the fEPSP response in trained compared to untrained animals while fiber volley size remained unchanged. The findings provide evidence for a direct implication of homosynaptic hippocampal long-term depression in a spatial learning paradigm.

Animals↗
PubMed2006

The stamp of ancestry: roots of behavioral and neuronal impairment in adulthood.

Exposure of pregnant animals to noxious conditions affects neuronal function in the offspring. However, exposure or treatment of the maternal animal during pregnancy affects both ancestor and offspring. In the present study, female CD-1 mice were repetitively treated with 3-nitropropionate (3-np), a selective inhibitor of succinic dehydrogenase, exclusively prior to mating. Clinically, mice appeared normal during treatment. Five days after cessation of treatment animals were mated with control male animals. At 4 months of age spatial learning, LTP, NADH autofluorescence, and hypoxic tolerance were alike in controls and the offspring of treated female ancestors. However, an additional metabolic challenge in the offspring unmasks impairment of spatial learning, diminution of long-term potentiation (LTP), an altered protein microenvironment of mitochondrial enzymes, and reduced hypoxic tolerance. We conclude that the exposure of maternal ancestors to subclinical repetitive impairment of oxidative phosphorylation fosters impairment of behavior and neuronal function in the adult offspring, becoming apparent only on additional challenge. This finding may ultimately help to understand the causes of neuronal impairment or even neuropsychiatric disease in old age.

Age Factors↗
PubMed2005

Ischemic preconditioning ameliorates excitotoxicity by shifting glutamate/gamma-aminobutyric acid release and biosynthesis.

Excitotoxicity is recognized to play a major role in cerebral ischemia-induced cell death. The main goal of the present study was to define whether our model of ischemic preconditioning (IPC) promotes a shift from excitatory to inhibitory neurotransmission during the test ischemia to diminish metabolic demand during the reperfusion phase. We also determined whether gamma-aminobutyric acid (GABA) played a role in IPC-induced neuroprotection. Ten minutes of cerebral ischemia was produced by tightening the carotid ligatures bilaterally following hypotension. Samples of microdialysis perfusate, representing extracellular fluid, were analyzed for amino acid content by HPLC. IPC promoted a robust release of GABA after lethal ischemia compared with control rats. We also observed that the activity of glutamate decarboxylase (the predominant pathway of GABA synthesis in the brain) was higher in the IPC group compared with control and ischemic groups. Because GABAA receptor up-regulation has been shown to occur following IPC, and GABAA receptor activation has been implicated in neuroprotection against ischemic insults, we tested the hypothesis that GABAA or GABAB receptor activation was neuroprotective during ischemia or early reperfusion by using an in vitro model (organotypic hippocampal slice culture). Administration of the GABAB agonist baclofen during test ischemia and for 1 hr of reperfusion provided significant neuroprotection. We concluded that increased GABA release in preconditioned animals after ischemia might be one of the factors responsible for IPC neuroprotection. Specific activation of GABAB receptor contributes significantly to neuroprotection against ischemia in organotypic hippocampal slices.

Animals↗
PubMed2005

Anterior limbic alpha-like activity: a low resolution electromagnetic tomography study with lorazepam challenge.

OBJECTIVE: To verify findings of an independently regulated anterior limbic alpha band source. METHODS: In a randomised cross-over study, the spontaneous EEG was recorded in nine healthy subjects after i.v. lorazepam or placebo. Intracerebral current densities within classical frequency bands were estimated with low resolution electromagnetic tomography [LORETA] and compared between groups with t-statistical parametric mapping [SPM[t]]. A region-of-interest [ROI] based method was used to compare frontal and occipital alpha band activity changes. RESULTS: Irrespective of treatment group, local maxima of alpha band power were localised both in the occipital lobe, Brodman area [BA] 18, and in the anterior cingulate cortex [ACC], BA 32. Statistical parametric mapping showed reduced parieto-occipital, but unaltered frontal alpha band power after lorazepam. This result was confirmed by ROI-based comparison of BA 18 and BA 32. CONCLUSIONS: There was an anterior limbic maximum of alpha band activity which, unlike occipital alpha, was not suppressed by lorazepam. SIGNIFICANCE: The well-known anterior alpha band components may originate from a narrowly circumscribed source, located in the ACC. Frontal and occipital alpha band activities appear to be independently regulated.

Adult↗
PubMed2004

The thalamus as the generator and modulator of EEG alpha rhythm: a combined PET/EEG study with lorazepam challenge in humans.

BACKGROUND: Purpose of this study was to investigate the functional relationship between electroencephalographic (EEG) alpha power and cerebral glucose metabolism before and after pharmacological alpha suppression by lorazepam. METHODS: Ten healthy male volunteers were examined undergoing two F18-fluorodeoxyglucose (18-FDG) positron emission tomography (PET) scans with simultaneous EEG recording: 1x placebo, 1x lorazepam. EEG power spectra were computed by means of Fourier analysis. The PET data were analyzed using SPM99, and the correlations between metabolism and alpha power were calculated for both conditions. RESULTS: The comparison lorazepam versus placebo revealed reduced glucose metabolism of the bilateral thalamus and adjacent subthalamic areas, the occipital cortex and temporo-insular areas (P < 0.001). EEG alpha power was reduced in all derivations (P < 0.001). Under placebo, there was a positive correlation between alpha power and metabolism of the bilateral thalamus and the occipital and adjacent parietal cortex (P < 0.001). Under lorazepam, the thalamic and parietal correlations were maintained, whereas the occipital correlation was no longer detectable (P < 0.001). The correlation analysis of the difference lorazepam-placebo showed the alpha power exclusively correlated with the thalamic activity (P < 0.0001). CONCLUSIONS: These results support the hypothesis of a close functional relationship between thalamic activity and alpha rhythm in humans mediated by corticothalamic loops which are independent of sensory afferences. The study paradigm could be a promising approach for the investigation of cortico-thalamo-cortical feedback loops in neuropsychiatric diseases.

Adult↗
PubMed2004

Epsilon protein kinase C mediated ischemic tolerance requires activation of the extracellular regulated kinase pathway in the organotypic hippocampal slice.

Ischemic preconditioning (IPC) promotes brain tolerance against subsequent ischemic insults. Using the organotypic hippocampal slice culture, we conducted the present study to investigate (1) the role of adenosine A1 receptor (A1AR) activation in IPC induction, (2) whether epsilon protein kinase C (epsilonPKC) activation after IPC is mediated by the phosphoinositol pathway, and (3) whether epsilonPKC protection is mediated by the extracellular signal-regulated kinase (ERK) pathway. Our results demonstrate that activation of A1AR emulated IPC, whereas blockade of the A1AR during IPC diminished neuroprotection. The neuroprotection promoted by the A1AR was also reduced by the epsilonPKC antagonist. To determine whether epsilonPKC activation in IPC and A1AR preconditioning is mediated by activation of the phosphoinositol pathway, we incubated slices undergoing IPC or adenosine treatment with a phosphoinositol phospholipase C inhibitor. In both cases, preconditioning neuroprotection was significantly attenuated. To further characterize the subsequent signal transduction pathway that ensues after epsilonPKC activation, mitogen-activated protein kinase kinase was blocked during IPC and pharmacologic preconditioning (PPC) (with epsilonPKC, NMDA, or A1AR agonists). This treatment significantly attenuated IPC- and PPC-induced neuroprotection. In conclusion, we demonstrate that epsilonPKC activation after IPC/PPC is essential for neuroprotection against oxygen/glucose deprivation in organotypic slice cultures and that the ERK pathway is downstream to epsilonPKC.

Animals↗
PubMed2003

Symptom-triggered versus standard chlormethiazole treatment of inpatient alcohol withdrawal: clinical implications from a chart analysis.

To evaluate clinical effectiveness and safety of 2 different detoxification treatment protocols, a chart analysis of hospital inpatients consecutively admitted for alcohol withdrawal during one year was undertaken. Records of 33 patients receiving symptom-triggered treatment (using a modified version of the revised Clinical Institute Withdrawal Assessment for Alcohol Scale) were compared with those of patients treated by applying a fixed-dose regimen (n = 32). Patients (45.3 +/- 9.8 years, 21% female) of both groups were comparable regarding illness severity, epidemiologic parameters as well as complications during the observed treatment period. Under symptom-triggered therapy, chlormethiazole (CMZ) treatment duration (4.2 +/- 3.5 vs. 7.5 +/- 3.3 days, Mann-Whitney U test: p = 0.0003) and cumulative CMZ dosage (4352 +/- 4589 vs. 9921 +/- 6599 mg, Mann-Whitney U test: p = 0.0004) were significantly reduced. The daily CMZ dose was significantly lower at days 1-5 in the group receiving symptom-triggered treatment. There was no influence of age on the outcome parameters of either treatment group. In conclusion, an individualized symptom-triggered treatment of alcohol withdrawal with CMZ seems to be equally safe but more efficient than a scheduled regimen.

Adult↗
PubMedDate not supplied

Ischemic tolerance induction in organotypic hippocampal slices: role for the GABA(A) receptor?

Ischemic preconditioning (IPC) refers to sublethal ischemic insults rendering brain tissue tolerant against subsequent ischemic insults. We investigated the role of the GABA(A) receptor (GABA(A)R) upon IPC induction. Rat organotypic hippocampal slices were subjected to IPC by 15 min of oxygen-glucose deprivation (OGD) followed by 40 min of OGD 48 h later, resulting in robust cell death reduction as assessed by the propidium iodide fluorescence method ('late' or 'second window' IPC). Superfusion with the GABA(A)R antagonist bicuculline during IPC ameliorated propidium iodide uptake at a high but not at low doses indicating that GABA(A)R activation may be assigned a limited role in neuroprotection. In previous studies, we found that increased neuronal excitability can promote IPC neuroprotection. We, therefore, tested the hypothesis that blockade of inhibitory GABAergic transmission conferred ischemic tolerance. However, temporary administration of bicuculline 48 h prior to ischemic challenge was not neuroprotective. In another approach, we tested whether preconditioning with the GABA(A)R agonist, 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP) mediated ischemic tolerance and found no significant neuroprotection. The results are discussed in light of the intrinsic excitatory-inhibitory balance of glutamate and GABA.

Animals↗