scholarly journals A post‐mortem study of melanin‐concentrating hormone (MCH) neurons in Alzheimer’s disease and progressive supranuclear palsy: The complex degeneration pattern of the lateral hypothalamic area

2021 ◽  
Vol 17 (S6) ◽  
Author(s):  
Mihovil Mladinov ◽  
Jun Yeop Oh ◽  
Cathrine Petersen ◽  
Rana April Eser ◽  
Song Li ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Progressive Supranuclear Palsy ◽  
Lateral Hypothalamic Area ◽  
Post Mortem ◽  
Hypothalamic Area ◽  
Lateral Hypothalamic ◽  
Melanin Concentrating Hormone

scholarly journals Specific pattern of melanin-concentrating hormone (MCH) neuron degeneration in Alzheimer’s disease and possible clinical implications

2021 ◽  
Author(s):  
Mihovil Mladinov ◽  
Jun Yeop Oh ◽  
Cathrine Petersen ◽  
Rana Eser ◽  
Song Hua Li ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Progressive Supranuclear Palsy ◽  
Functional Relation ◽  
Lateral Hypothalamic Area ◽  
Future Research ◽  
Hypothalamic Area ◽  
Lateral Hypothalamic ◽  
New Findings ◽  
Melanin Concentrating Hormone

ABSTRACTStudy ObjectivesThe lateral hypothalamic area (LHA) is one of the key regions orchestrating sleep and wake control. It is the site of wake-promoting orexinergic and sleep-promoting melanin-concentrating hormone (MCH) neurons, which share a close anatomical and functional relation. The aim of the study was to investigate the degeneration of MCH neurons in Alzheimer’s disease (AD) and progressive supranuclear palsy (PSP), and relate the new findings to our previously reported pattern of degeneration of wake-promoting orexinergic neuronsMethodsPost-mortem human brain tissue of subjects with AD, PSP and controls was examined using unbiased stereology. Double immunohistochemistry with MCH- and tau-antibodies on formalin-fixed, celloidin embedded tissue was performed.ResultsThere was no difference in the total number of MCH neurons between AD, PSP and controls, but a significant loss of non-MCH neurons in AD patients (p=0.019). The proportion of MCH neurons was significantly higher in AD (p=0.0047). No such a difference was found in PSP. In PSP, but not AD, the proportion of tau+ MCH neurons was lower than the proportion of tau+ non-MCH neurons (p=0.002). When comparing AD to PSP, the proportion of tau+MCH neurons was higher in AD (p<0.001).ConclusionsMCH neurons are more vulnerable to AD than PSP pathology. High burden of tau-inclusions, but comparably milder loss of MCH neurons in AD, together with previously reported orexinergic neuronal loss may lead to a hyperexcitability of the MCH system in AD, contributing to wake-sleep disorders in AD. Further experimental research is needed to understand why MCH neurons are more resistant to tau-toxicity compared to orexinergic neurons.STATEMENT OF SIGNIFICANCEThis is the first study to investigate the involvement of melanin-concentrating hormone (MCH) neurons in patients with Alzheimer’s disease and progressive supranuclear palsy. MCH neurons are key regulators of sleep and metabolic functions, and one of the major neuronal populations of the lateral hypothalamic area (LHA), but still underexplored in humans. Uncovering the pathology of this neuronal population in neurodegenerative disorders will improve our understanding of the complex neurobiology of the LHA and the interaction between MCH and orexinergic neurons. This new knowledge may open new strategies for treatment interventions. Further, this study represents a fundament for future research on MCH neurons and the LHA in tauopathies.

scholarly journals Lateral Hypothalamic Area Glutamatergic Neurons and Their Projections to the Lateral Habenula Modulate the Anesthetic Potency of Isoflurane in Mice

2021 ◽  
Author(s):  
Shiyi Zhao ◽  
Rui Li ◽  
Huiming Li ◽  
Sa Wang ◽  
Xinxin Zhang ◽  
...  
Keyword(s):  
Large Population ◽  
Lateral Hypothalamic Area ◽  
Hypothalamic Area ◽  
Lateral Habenula ◽  
Genetic Ablation ◽  
Glutamatergic Neurons ◽  
Lateral Hypothalamic ◽  
Melanin Concentrating Hormone ◽  
Anesthetic Potency ◽  
Eeg Features

AbstractThe lateral hypothalamic area (LHA) plays a pivotal role in regulating consciousness transition, in which orexinergic neurons, GABAergic neurons, and melanin-concentrating hormone neurons are involved. Glutamatergic neurons have a large population in the LHA, but their anesthesia-related effect has not been explored. Here, we found that genetic ablation of LHA glutamatergic neurons shortened the induction time and prolonged the recovery time of isoflurane anesthesia in mice. In contrast, chemogenetic activation of LHA glutamatergic neurons increased the time to anesthesia and decreased the time to recovery. Optogenetic activation of LHA glutamatergic neurons during the maintenance of anesthesia reduced the burst suppression pattern of the electroencephalogram (EEG) and shifted EEG features to an arousal pattern. Photostimulation of LHA glutamatergic projections to the lateral habenula (LHb) also facilitated the emergence from anesthesia and the transition of anesthesia depth to a lighter level. Collectively, LHA glutamatergic neurons and their projections to the LHb regulate anesthetic potency and EEG features.

scholarly journals Defining early changes in Alzheimer’s disease from RNA sequencing of brain regions differentially affected by pathology

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Boris Guennewig ◽  
Julia Lim ◽  
Lee Marshall ◽  
Andrew N. McCorkindale ◽  
Patrick J. Paasila ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rna Sequencing ◽  
Neuronal Loss ◽  
Brain Regions ◽  
Post Mortem ◽  
Tau Pathology ◽  
Membrane Spanning ◽  
Immune Related Genes ◽  
Vesicle Secretion

AbstractTau pathology in Alzheimer’s disease (AD) spreads in a predictable pattern that corresponds with disease symptoms and severity. At post-mortem there are cortical regions that range from mildly to severely affected by tau pathology and neuronal loss. A comparison of the molecular signatures of these differentially affected areas within cases and between cases and controls may allow the temporal modelling of disease progression. Here we used RNA sequencing to explore differential gene expression in the mildly affected primary visual cortex and moderately affected precuneus of ten age-, gender- and RNA quality-matched post-mortem brains from AD patients and healthy controls. The two regions in AD cases had similar transcriptomic signatures but there were broader abnormalities in the precuneus consistent with the greater tau load. Both regions were characterised by upregulation of immune-related genes such as those encoding triggering receptor expressed on myeloid cells 2 and membrane spanning 4-domains A6A and milder changes in insulin/IGF1 signalling. The precuneus in AD was also characterised by changes in vesicle secretion and downregulation of the interneuronal subtype marker, somatostatin. The ‘early’ AD transcriptome is characterised by perturbations in synaptic vesicle secretion on a background of neuroimmune dysfunction. In particular, the synaptic deficits that characterise AD may begin with the somatostatin division of inhibitory neurotransmission.

Alteration of the expression of the hypocretin (orexin) gene by 2-deoxyglucose in the rat lateral hypothalamic area

Neuroreport ◽  
2000 ◽  
Vol 11 (3) ◽  
pp. 531-533 ◽  
Author(s):  
Laurence Bayer ◽  
Claude Colard ◽  
Nhu Uyen Nguyen ◽  
Pierre-Yves Risold ◽  
Dominique Fellmann ◽  
...  
Keyword(s):  
Lateral Hypothalamic Area ◽  
Hypothalamic Area ◽  
Lateral Hypothalamic
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