Effects of the excitation or inhibition of basal forebrain cholinergic neurons on cognitive ability in mice exposed to chronic intermittent hypoxia

Tang, Si; Zhu, Jing; Zhao, Dong; Mo, Huaheng; Zeng, Zhaofu; Xiong, Mengqing; Dong, Minglin; Hu, Ke

doi:10.1016/j.brainresbull.2020.08.027

“…The NTS is a primary first site for upper airway and swallow-related sensory termination in the brainstem ( Jean, 1984 ). CIH induces changes to the cardio-respiratory Vglut2 neurons, resulting in an increase in cNTS neuronal activity ( Kline, 2010 ; Kline et al, 2007 ), as well as changes to preBötC neurons ( Garcia et al, 2017 ; Garcia et al, 2016 ) and ChAT neurons in the basal forebrain ( Tang et al, 2020 ). It is reasonable to suggests that CIH has differential effects on neurons that only express ChATcre and Vglut2cre versus the PiCo-specific interneurons that co-express ChATcre and Vglut2FlpO, emphasizing the importance of targeting and manipulating these PiCo-specific interneurons.…”

Section: Discussionmentioning

confidence: 99%

Chronic intermittent hypoxia reveals role of the Postinspiratory Complex in the mediation of normal swallow production

Huff,

Karlen-Amarante,

Oliveira

et al. 2024

eLife

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Obstructive sleep apnea (OSA) is a prevalent sleep-related breathing disorder that results in multiple bouts of intermittent hypoxia. OSA has many neurologic and systemic comorbidities including dysphagia, or disordered swallow and discoordination with breathing. However, the mechanism in which chronic intermittent hypoxia (CIH) causes dysphagia is unknown. Recently we showed the Postinspiratory complex (PiCo) acts as an interface between the swallow pattern generator (SPG) and the inspiratory rhythm generator, the preBötzinger Complex, to regulate proper swallow-breathing coordination (A. D. Huff et al., 2023). PiCo is characterized by interneurons co-expressing transporters for glutamate (Vglut2) and acetylcholine (ChAT). Here we show that optogenetic stimulation of ChATcre:Ai32, Vglut2cre:Ai32, and ChATcre:Vglut2FlpO:ChR2 mice exposed to CIH does not alter swallow-breathing coordination, but unexpectedly the generation of swallow motor pattern was significantly disturbed. This suggests, glutamatergic-cholinergic neurons in PiCo are not only critical for the gating of postinspiratory and swallow activity, but also play important roles in the generation of swallow motor pattern. Our study also suggests that swallow disruption, as seen in OSA involves central nervous mechanisms interfering with the generation of the swallow pattern and laryngeal activation. These findings are crucial for understanding the mechanisms underlying dysphagia in OSA and other breathing and neurological disorders.

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“…The NTS is a primary first site for upper airway and swallow-related sensory termination in the brainstem (Jean, 1984). CIH induces changes to the cardio-respiratory Vglut2 neurons, resulting in an increase in cNTS neuronal activity (Kline, 2010; Kline et al, 2007), as well as changes to preBötzinger complex neurons (Garcia et al, 2017; Garcia et al, 2016) and ChAT neurons in the basal forebrain (Tang et al, 2020). It is reasonable to suggests that CIH has differential effects on neurons that only express ChATcre and Vglut2cre versus the PiCo-specific interneurons that co-express ChATcre and Vglut2FlpO, emphasizing the importance of targeting and manipulating these PiCo-specific interneurons.…”

Section: Discussionmentioning

confidence: 99%

Chronic Intermittent Hypoxia reveals role of the Postinspiratory Complex in the mediation of normal swallow production

Huff,

Karlen-Amarante,

Oliveira

et al. 2023

Preprint

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Obstructive sleep apnea (OSA) is a prevalent sleep-related breathing disorder that results in multiple bouts of intermittent hypoxia. OSA has many neurologic and systemic comorbidities including dysphagia, or disordered swallow and discoordination with breathing. However, the mechanism in which chronic intermittent hypoxia (CIH) causes dysphagia is unknown. Recently we showed the Postinspiratory complex (PiCo) acts as an interface between the swallow pattern generator (SPG) and the inspiratory rhythm generator, the preBötzinger Complex, to regulate proper swallow-breathing coordination (A. D. Huff et al., 2023). PiCo is characterized by interneurons co-expressing transporters for glutamate (Vglut2) and acetylcholine (ChAT). Here we show that optogenetic stimulation of ChATcre:Ai32, Vglut2cre:Ai32, and ChATcre:Vglut2FlpO:ChR2 mice exposed to CIH does not alter swallow-breathing coordination, but unexpectedly the generation of swallow motor pattern was significantly disturbed. This suggests, glutamatergic-cholinergic neurons in PiCo are not only critical for the gating of postinspiratory and swallow activity, but also play important roles in the generation of swallow motor pattern. Our study also suggests that swallow disruption, as seen in OSA involves central nervous mechanisms interfering with the generation of the swallow pattern and laryngeal activation. These findings are crucial for understanding the mechanisms underlying dysphagia in OSA and other breathing and neurological disorders.

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“…Of the 48 included animal studies, 28 (58.5%) observed adverse effects of hypoxia exposure [27][28][29]31,32,35,36,[38][39][40][41]46,47,49,50,57,59,[61][62][63][64]66,67,[69][70][71][72], while 18 studies (37.5%) reported beneficial effects [26,33,34,37,[42][43][44][45]48,51,53,55,56,58,60,65,68,73] and two studies (4%) found either no change in outcomes or mixed findings in both directions after hypoxia treatment [30,52].…”

Section: Effects Of Moderate Hypoxia In Animal Studiesmentioning

confidence: 99%

“…Thirty-eight studies investigated the effects of moderate hypoxia exposure on cognitive functioning and anxiety-and depression-like behavior in rodents (see Table 2). Thirty-three studies examined hypoxia-related changes in hippocampal-dependent learning and memory performance, mostly assessed with the Morris water maze paradigm (27 of 33 studies) [30][31][32][34][35][36][38][39][40][41][42]44,45,50,51,[54][55][56][57][59][60][61][62][63][64][65]72]. Of these, 21 studies reported impaired learning and memory following various protocols with higher doses of hypoxia, including normobaric intermittent hypoxia (mainly 10% O 2 ) chronically administered for +10 h daily over 2-4 weeks, or hypobaric continuous hypoxia of 11-13% O 2 chronically administered over 4-12 weeks [31,32,35,36,[38][39][40][41]50,54,57,59,[61][62][63][64]…”

Section: Cognition and Neuropsychiatric Behaviormentioning

confidence: 99%

“…Finally, 11 reports studied hypoxia-related effects on anxiety-and depression-like behavior, and locomotor functioning, which was mostly assessed with the open field test paradigm [27,39,44,45,50,57,61,67,68,71,73]. Of these, four studies found reduced anxious and depressive behavior (e.g., more time spent in open arms and physical state of fur) after 4 h daily continuous hypobaric 10.8-16% O 2 repeated for 2-4 weeks [44,45,68,73].…”

Section: Cognition and Neuropsychiatric Behaviormentioning

confidence: 99%

See 1 more Smart Citation

Neuroprotective Effects of Moderate Hypoxia: A Systematic Review

Damgaard,

Mariegaard,

Lindhardsen

et al. 2023

Brain Sciences

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0

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Emerging evidence highlights moderate hypoxia as a candidate treatment for brain disorders. This systematic review examines findings and the methodological quality of studies investigating hypoxia (10–16% O2) for ≥14 days in humans, as well as the neurobiological mechanisms triggered by hypoxia in animals, and suggests optimal treatment protocols to guide future studies. We followed the preferred reporting items for systematic reviews and meta-analysis (PRISMA) 2020. Searches were performed on PubMed/MEDLINE, PsycInfo, EMBASE, and the Cochrane Library, in May–September 2023. Two authors independently reviewed the human studies with the following tools: (1) revised Cochrane collaboration’s risk of bias for randomized trials 2.0; (2) the risk of bias in nonrandomized studies of interventions. We identified 58 eligible studies (k = 8 human studies with N = 274 individuals; k = 48 animal studies) reporting the effects of hypoxia on cognition, motor function, neuroimaging, neuronal/synaptic morphology, inflammation, oxidative stress, erythropoietin, neurotrophins, and Alzheimer’s disease markers. A total of 75% of human studies indicated cognitive and/or neurological benefits, although all studies were evaluated ashigh risk of bias due to a lack of randomization and assessor blinding. Low-dose intermittent or continuous hypoxia repeated for 30–240 min sessions, preferably in combination with motor-cognitive training, produced beneficial effects, and high-dose hypoxia with longer (≥6 h) durations and chronic exposure produced more adverse effects. Larger and methodologically stronger translational studies are warranted.

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Effects of the excitation or inhibition of basal forebrain cholinergic neurons on cognitive ability in mice exposed to chronic intermittent hypoxia

Cited by 9 publications

References 37 publications

Chronic intermittent hypoxia reveals role of the Postinspiratory Complex in the mediation of normal swallow production

Chronic intermittent hypoxia reveals role of the Postinspiratory Complex in the mediation of normal swallow production

Chronic Intermittent Hypoxia reveals role of the Postinspiratory Complex in the mediation of normal swallow production

Neuroprotective Effects of Moderate Hypoxia: A Systematic Review

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