Fornix deep brain stimulation enhances acetylcholine levels in the hippocampus

Deep brain stimulation (DBS) of the fornix has gained interest as a potential therapy for advanced treatment-resistant dementia, yet the mechanism of action remains widely unknown. Previously, we have reported beneficial memory effects of fornix DBS in a scopolamine induced rat model of dementia, which is dependent on various brain structures including hippocampus. To elucidate mechanisms of action of fornix DBS with regard to memory restoration, we performed c-Fos immunohistochemistry in the hippocampus. We found that fornix DBS induced a selective activation of cells in the CA1 and CA3 subfields of the dorsal hippocampus. In addition, hippocampal neurotransmitter levels were measured using microdialysis before, during and after 60 min of fornix DBS in a next experiment. We observed a substantial increase in the levels of extracellular hippocampal acetylcholine, which peaked 20 min after stimulus onset. Interestingly, hippocampal glutamate levels did not change compared to baseline. Therefore, our findings provide first experimental evidence that fornix DBS activates the hippocampus and induces the release of acetylcholine in this region.Publisher PDFPeer reviewe

The Alteration of Neurogenesis and Pathological Markers in Alzheimer's Disease After Deep Brain Stimulation

Alzheimer's disease (AD) is the most common type of dementia that causes disabilities in memory formation and activities of daily living. Unfortunately, pharmacologic treatments have minimal and short-lasting effects on AD. With the increasing aging population, investigations into therapeutic strategies for AD that lead to a delay in disease progression would significantly reduce the global burden of AD. Deep brain stimulation (DBS) is considered therapeutic for several conditions, such as movement disorders and some psychiatric diseases. Preclinical and clinical studies that used DBS as a treatment modality demonstrate the safety of DBS in AD and suggest potential memory improvements after surgery. Nevertheless, more studies are needed to understand the therapeutic mechanism of DBS. In this review, we summarize studies on DBS in various targets for AD and discuss DBS-induced changes in neurogenesis and pathological markers in AD

Environmental changes during the last millennium based on multi-proxy palaeoecological records in a savanna-forest mosaic from the northernmost Brazilian Amazon region

ABSTRACTThe environmental changes and the dynamics of the savanna-forest mosaic, over the last 1050 years, have been reconstructed by pollen, charcoal, radiocarbon dating mineralogical and geochemical analyses of sediment cores taken from three different Mauritia flexuosapalm swamps in the northernmost part of the Brazilian Amazon region (northern state of Roraima). Studies on the relationship between the modern pollen rain and the regional vegetation provide additional information for the interpretation of the fossil pollen records. The fossil pollen assemblages and geochemical results indicate relatively wet climatic conditions throughout the recorded period. Despite these moist conditions, fires were frequent and are one of the reasons for the dominance of a grassy savanna instead of forest expansion in the study area. Considering the generally wet climatic conditions, these fires were most likely caused by human activities. Even today, fires hinder forest expansion into savanna areas. Sandy hydromorphic soils may also act as an edaphic control to maintain the current sharp boundary between forest and savanna ecosystems

Deep brain stimulation of the nucleus basalis of Meynert in an experimental rat model of dementia: Stimulation parameters and mechanisms

Background/objective: Deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM) has gained interest as a potential therapy for treatment-resistant dementia. However, optimal stimulation parameters and mechanisms of action are yet to be elucidated. Methods: First, we assessed NBM DBS at different stimulation parameters in a scopolamine-induced rat model of dementia. Rats were tested in the object location task with the following conditions: (i) low and high frequency (20 Hz or 120 Hz), (ii) monophasic or biphasic pulse shape (iii) continuous or intermittent DBS (20s on, 40s off) and 100 mu A amplitude. Thereafter, rats were stimulated with the most effective parameter followed by 5-bromo-2 '-deoxyuridine (BrdU) administration and perfused 4 weeks later. We then evaluated the effects of NBM DBS on hippocampal neurogenesis, synaptic plasticity, and on cholinergic fibres in the perirhinal and cingulate cortex using immunohistochemistry. We also performed in-vivo microdialysis to assess circuit-wide effects of NBM DBS on hippocampal acetylcholine levels during on and off stimulation. Results: Biphasic, low frequency and intermittent NBM DBS reversed the memory impairing effects of scopolamine when compared to sham rats. We found that acute stimulation promoted proliferation in the dentate gyrus, increased synaptic plasticity in the CA1 and CA3 subregion of the hippocampus, and increased length of cholinergic fibres in the cingulate gyrus. There was no difference regarding hippocampal acetylcholine levels between the groups. Conclusion: These findings suggest that the potential mechanism of action of the induced memory enhancement through NBM DBS might be due to selective neuroplastic and neurochemical changes

Deep brain stimulation of the nucleus basalis of Meynert in an experimental rat model of dementia: Stimulation parameters and mechanisms

Background/objective: Deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM) has gained interest as a potential therapy for treatment-resistant dementia. However, optimal stimulation parameters and mechanisms of action are yet to be elucidated. Methods: First, we assessed NBM DBS at different stimulation parameters in a scopolamine-induced rat model of dementia. Rats were tested in the object location task with the following conditions: (i) low and high frequency (20 Hz or 120 Hz), (ii) monophasic or biphasic pulse shape (iii) continuous or intermittent DBS (20s on, 40s off) and 100 μA amplitude. Thereafter, rats were stimulated with the most effective parameter followed by 5-bromo-2′-deoxyuridine (BrdU) administration and perfused 4 weeks later. We then evaluated the effects of NBM DBS on hippocampal neurogenesis, synaptic plasticity, and on cholinergic fibres in the perirhinal and cingulate cortex using immunohistochemistry. We also performed in-vivo microdialysis to assess circuit-wide effects of NBM DBS on hippocampal acetylcholine levels during on and off stimulation. Results: Biphasic, low frequency and intermittent NBM DBS reversed the memory impairing effects of scopolamine when compared to sham rats. We found that acute stimulation promoted proliferation in the dentate gyrus, increased synaptic plasticity in the CA1 and CA3 subregion of the hippocampus, and increased length of cholinergic fibres in the cingulate gyrus. There was no difference regarding hippocampal acetylcholine levels between the groups. Conclusion: These findings suggest that the potential mechanism of action of the induced memory enhancement through NBM DBS might be due to selective neuroplastic and neurochemical changes