Article
Biology
Maria Luisa Franco, Irmina Garcia-Carpio, Raquel Comaposada-Baro, Juan J. Escribano-Saiz, Lucia Chavez-Gutierrez, Marcal Vilar
Summary: Research shows that treatment with gamma-secretase inhibitors leads to the oligomerization of p75CTF, resulting in cell death of BFCNs, possibly mediated by TrkA activity. The findings suggest that inhibiting gamma-secretase activity in older patients may accelerate cholinergic dysfunction and neurodegeneration.
LIFE SCIENCE ALLIANCE
(2021)
Article
Behavioral Sciences
Anne S. Berry, Theresa M. Harrison
Summary: The basal forebrain cholinergic system (BFCS) has been associated with age-related cognitive changes and Alzheimer's disease (AD). Despite limitations in cholinergic interventions, there is a renewed interest in studying the BFCS using novel frameworks. This article outlines the structure and function of the BFCS, its role in cognition and emotion, and its vulnerability to aging and AD. It also explores the BFCS in relation to the amyloid hypothesis, selective vulnerability, pathology spread, and sleep health in AD research.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2023)
Review
Cell Biology
Erika Kropf, Margaret Fahnestock
Summary: Nerve growth factor (NGF) and its precursor, proNGF, play critical roles in neuronal survival and cognitive function. Dysregulation of proNGF may contribute to age-related memory loss and Alzheimer's disease. Increased reactive oxygen and nitrogen species (ROS/RNS) in the brain may impair proNGF transport and signalling, leading to vulnerability of the basal forebrain in AD. Antioxidant treatments may help restore proNGF signalling and reduce neurodegeneration and cognitive deficits in the basal forebrain.
Article
Neurosciences
Selena Gonzalez, Tyne L. M. McHugh, Tao Yang, Wassim Syriani, Stephen M. Massa, Frank M. Longo, Danielle A. Simmons
Summary: The study identified a new drug, PTX-BD10-2, that can help restore symptomatic neuron degeneration in an Alzheimer's disease mouse model and has neuroprotective effects on neurons derived from human induced pluripotent stem cells.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Multidisciplinary Sciences
Yuko Kondo-Takuma, Masayuki Mizuno, Yo Tsuda, Yuta Madokoro, Kengo Suzuki, Toyohiro Sato, Hiroshi Takase, Yuto Uchida, Ken-Ichi Adachi, Hideki Hida, Cesario Borlongan, Noriyuki Matsukawa
Summary: The cholinergic efferent network from the medial septal nucleus to the hippocampus is important for learning and memory processes. HCNP, a peptide involved in acetylcholine synthesis, plays a role in regulating acetylcholine release and incorporation into synaptic vesicles in the hippocampus. Knockout mice lacking HCNP-pp exhibited reduced acetylcholine release and levels of vesicular acetylcholine transporter in the hippocampus, indicating a potential role for HCNP in the cholinergic regulation of the septo-hippocampal network.
SCIENTIFIC REPORTS
(2021)
Article
Clinical Neurology
Rok Berlot, Blaz Koritnik, Zvezdan Pirtosek, Nicola J. Ray
Summary: Neurodegeneration causes redistribution of information processing, impacting the reorganization of the structural connectome and vulnerability. Cortical acetylcholine aids in adapting to pathology within the memory circuit, but its broader impact on whole-brain networks is uncertain. Larger volumes of the cholinergic basal forebrain (CBFB) in patients with mild cognitive impairment (MCI) are associated with efficient network topology and reduced impact of specific lesions, suggesting a protective effect against the global impact of simulated strategic lesions.
JOURNAL OF THE NEUROLOGICAL SCIENCES
(2021)
Article
Clinical Neurology
Chenqing Wu, Haoting Wu, Cheng Zhou, Xiaojun Guan, Tao Guo, Zhengye Cao, Jingjing Wu, Xiaocao Liu, Jingwen Chen, Jiaqi Wen, Jianmei Qin, Sijia Tan, Xiaojie Duanmu, Weijin Yuan, Qianshi Zheng, Baorong Zhang, Peiyu Huang, Xiaojun Xu, Minming Zhang
Summary: This study reveals that the degeneration of the cholinergic basal forebrain system in Parkinson's disease patients is associated with postural instability/gait difficulty and cognitive impairment.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Neurosciences
Gaq Tu, Adel Halawa, Xiaotian Yu, Samuel Gillman, Kaori Takehara-Nishiuchi
Summary: Acetylcholine controls arousal, attention, and learning through regulating cortical excitability and plasticity. Recent research found that cholinergic neurons emit precise signals about aversive outcomes. This study manipulated cholinergic terminals in the mPFC and discovered that phasic cholinergic signaling plays a crucial role in aversive associative learning.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Jessica Peter, Isabella Mayer, Thomas Kammer, Lora Minkova, Jacob Lahr, Stefan Kloeppel, Michel J. Grothe, Michael Orth
Summary: The study showed that larger basal forebrain volume was associated with stronger SAI in healthy volunteers, while smaller basal forebrain volume was found in MCI patients, which was not associated with SAI.
SCIENTIFIC REPORTS
(2021)
Article
Clinical Neurology
Mikahela A. Lopez-Morales, Iris Escobar, Isabel Saul, Charles W. Jackson, Fernando J. Ferrier, Eric A. Fagerli, Ami P. Raval, Kunjan R. Dave, Miguel A. Perez-Pinzon
Summary: This study reveals that focal cerebral ischemia leads to the death of cholinergic neurons in memory-relevant nuclei of the basal forebrain, and resveratrol preconditioning can prevent this cell loss, improve memory performance, and preserve the functionality of memory-processing brain structures.
Article
Biology
Blaise Robert, Eyal Y. Kimchi, Yurika Watanabe, Tatenda Chakoma, Miao Jing, Yulong Li, Daniel B. Polley
Summary: Research shows that basal forebrain cholinergic neurons have different functional characteristics in different regions, broadcasting diverse modulatory signals to downstream brain regions.
Article
Clinical Neurology
Claire Andre, Marie-eve Martineau-Dussault, Veronique Daneault, Helene Blais, Sonia Frenette, Dominique Lorrain, Carol Hudon, Celyne Bastien, Dominique Petit, Alexandre Lafreniere, Cynthia Thompson, Jacques Montplaisir, Nadia Gosselin, Julie Carrier
Summary: This study investigated the associations between the volume of basal forebrain nuclei and REM sleep characteristics, and the impact of cognitive status on these links. The findings suggest that REM sleep disturbances may be an early manifestation of the degeneration of the basal forebrain cholinergic system, especially in participants with mild memory deficits.
ALZHEIMERS RESEARCH & THERAPY
(2023)
Article
Medicine, Research & Experimental
Yong-Xia Xu, Can Wang, Xiao-Die Li, Wen-Lu Guo, Guo-Ying Liu, Hua-Bing Zhang, Yan Sun, De-Fa Zhu, Qi Xu
Summary: Cognitive dysfunction is common in hypothyroid patients, even after sufficient levothyroxine replacement therapy. Cholinergic neurons play a role in this cognitive impairment. Activating the BF cholinergic neurons improves cognitive function through the BF-PFC and BF-hippocampus pathways.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Review
Biochemistry & Molecular Biology
Kornraviya Sankorrakul, Lei Qian, Wipawan Thangnipon, Elizabeth J. Coulson
Summary: Cholinergic basal forebrain (cBF) neurons are susceptible to degeneration due to the up-regulation of p75 neurotrophin receptor (p75(NTR)), which mediates neuronal death in conditions such as oxidative stress and hypoxia. The signalling pathways of p75(NTR) death in these environments overlap, suggesting a potential causal relationship.
JOURNAL OF NEUROCHEMISTRY
(2021)
Review
Neurosciences
Saravanan Subramaniam, David T. Blake, Christos Constantinidis
Summary: DBS has emerged as a potential treatment for memory and cognitive impairment in neurodegenerative diseases. Stimulating specific brain structures, such as the nucleus basalis of Meynert, can enhance cortical activity and potentially ameliorate neuropathological mechanisms associated with Alzheimer's disease. High-frequency, continuous stimulation may not be suitable for Alzheimer's disease, and lower stimulation frequency or intermittent patterns of stimulation may be more effective when targeting the cholinergic forebrain.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Clinical Neurology
Stephanie R. Shepheard, Vassilios Karnaros, Beben Benyamin, David W. Schultz, Megan Dubowsky, Joanne Wuu, Tim Chataway, Andrea Malaspina, Michael Benatar, Mary-Louise Rogers
Summary: The study suggests that urinary neopterin may serve as a marker for disease progression in ALS and has the potential to predict response to anti-inflammatory therapies.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Review
Biochemistry & Molecular Biology
Jacinta N. Conroy, Elizabeth J. Coulson
Summary: Neurotrophin signaling is crucial for normal nervous system development and function. Understanding the mechanism of high-affinity receptor generation will facilitate the development of pharmaceuticals for the treatment of nervous system disorders. Despite decades of research, the modulation mechanism of the high-affinity complex remains unclear.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Review
Neurosciences
Jeremy Hunt, Elizabeth J. Coulson, Rajendram Rajnarayanan, Henrik Oster, Aleksandar Videnovic, Oliver Rawashdeh
Summary: The use of animal models is crucial for understanding the mechanisms of Parkinson's disease. This review examines the extent to which different mouse models accurately reflect the sleep and circadian abnormalities observed in Parkinson's disease.
MOLECULAR NEURODEGENERATION
(2022)
Article
Multidisciplinary Sciences
Wei-Yun Shen, Cong Luo, Plinio Reinaldo Hurtado, Xiao-Jing Liu, Ru-Yi Luo, Hui Li, Zhao-Lan Hu, Jun-Mei Xu, Elizabeth J. Coulson, Ming Zhao, Xin-Fu Zhou, Ru-Ping Dai
Summary: This study found that the inappropriate expansion of antibody-secreting cells (ASCs) in systemic lupus erythematosus (SLE) is associated with the signaling of brain-derived neurotrophic factor precursor (proBDNF) and its receptor p75(NTR). By inhibiting proBDNF, p75(NTR), or specifically knocking out p75(NTR) in CD19(+) B cells, lupus mice can be treated, reducing the production of autoantibodies and kidney injury.
Review
Psychiatry
Ella Pearson, Dan Siskind, Ruth E. Hubbard, Emily H. Gordon, Elizabeth J. Coulson, Nicola Warren
Summary: Emerging evidence suggests that individuals with severe mental illness (SMI) are at an increased risk of frailty. This systematic review examined the prevalence and correlates of frailty, as well as the efficacy of interventions, in this population. The findings indicate a high prevalence of frailty among individuals with SMI, with associations to physical comorbidity, cognitive deficits, falls, and mortality. However, further research is needed to develop appropriate interventions for frailty in this population.
JOURNAL OF PSYCHIATRIC RESEARCH
(2022)
Meeting Abstract
Clinical Neurology
Laura Chapman, Stephanie Shepheard, Nick Verber, Martin Turner, Andrea Malaspina, Mary-Louise Rogers, Pamela Shaw
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Article
Health Policy & Services
Ella Pearson, Dan Siskind, Ruth Hubbard, Emily Gordon, Elizabeth Coulson, Urska Arnautovska, Nicola Warren
Summary: This study examines the prevalence and characteristics of frailty in individuals with treatment-resistant schizophrenia, revealing a high rate of frailty and a younger age of onset. Frailty is positively associated with age and severity of psychiatric illness. The findings suggest that routine frailty assessments can lead to appropriate interventions, potentially improving life expectancy and quality of life.
COMMUNITY MENTAL HEALTH JOURNAL
(2023)
Article
Geriatrics & Gerontology
Xiaoqing Alice Zhou, Grace Ngiam, Lei Qian, Kornraviya Sankorrakul, Elizabeth J. Coulson, Kai-Hsiang Chuang
Summary: Degeneration of cholinergic neurons in the basal forebrain (BF) is a contributing factor to cognitive impairment. However, the volume changes measured by structural MRI in the BF do not directly reflect the changes in cholinergic neurons.
NEUROBIOLOGY OF AGING
(2022)
Article
Biochemistry & Molecular Biology
Ramon Martinez-Marmol, YeJin Chai, Jacinta N. Conroy, Zahra Khan, Seong-Min Hong, Seon Beom Kim, Rachel S. Gormal, Dae Hee Lee, Jae Kang Lee, Elizabeth J. Coulson, Mi Kyeong Lee, Sun Yeou Kim, Frederic A. Meunier
Summary: The traditional medicinal mushroom Hericium erinaceus enhances peripheral nerve regeneration through neurotrophic activity. We identified N-de phenylethyl isohericerin (NDPIH) and hericene A as biologically active compounds from this mushroom that promote neurite outgrowth in hippocampal neurons. NDPIH acts through a neurotrophic pathway independent of TrkB with ERK1/2 activation, while hericene A acts through a novel pan-neurotrophic signaling pathway, leading to improved cognitive performance in mice.
JOURNAL OF NEUROCHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Leanne K. Winner, Mary-Louise Rogers, Marten F. Snel, Kim M. Hemsley
Summary: Sanfilippo syndrome is an autosomal recessive inherited disorder that causes dementia in children. Early symptoms include delayed language development, hyperactivity, and insomnia, followed by the loss of acquired skills. There are no approved treatments, and the disease usually leads to death by age 18. Newborn screening for Sanfilippo syndrome would allow for early diagnosis and treatment, but there is a need for tools and biomarkers to provide pre-symptomatic prognosis. This review discusses the development of biomarker assays for Sanfilippo syndrome based on known neuropathological pathways.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Neurosciences
Megan Dubowsky, Frances Theunissen, Jillian M. Carr, Mary-Louise Rogers
Summary: Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), is a progressive neurological disorder characterized by the death of upper and lower motor neurons. It is proposed that endogenous retroviruses (ERVs), specifically human endogenous retrovirus type K (HERV-K), play a role in the propagation of neurodegeneration in ALS. This review discusses the involvement of transactive response DNA binding protein 43 kDa (TDP-43), HERV-K, and immune regulators in the onset and progression of ALS, as well as the potential of targeting ERVs as a therapy for ALS.
MOLECULAR NEUROBIOLOGY
(2023)
Review
Clinical Neurology
Mary-Louise Rogers, David W. Schultz, Vassilios Karnaros, Stephanie R. Shepheard
Summary: Amyotrophic lateral sclerosis is a fatal neurodegenerative disease characterized by degeneration of upper and lower motor neurons. Finding fluid-based biomarkers that reflect the pathological processes is crucial for evaluating treatment efficacy, and urine may be a rich source of candidate biomarkers.
BRAIN COMMUNICATIONS
(2023)
Article
Geriatrics & Gerontology
Ying Xia, Paul Maruff, Vincent Dore, Pierrick Bourgeat, Simon M. Laws, Christopher Fowler, Stephanie R. Rainey-Smith, Ralph N. Martins, Victor L. Villemagne, Christopher C. Rowe, Colin L. Masters, Elizabeth J. Coulson, Jurgen Fripp
Summary: Dysfunction of the cholinergic basal forebrain system and amyloid-beta deposition are early pathological features in Alzheimer's disease. This study found that Aβ is associated with volume loss in the BF and hippocampus, and the effect varies within BF subregions. The degeneration of BF subregions during early AD also shows distinctive characteristics.
NEUROBIOLOGY OF AGING
(2023)
Article
Neuroimaging
Ying Xia, Eamonn Eeles, Jurgen Fripp, Donna Pinsker, Paul Thomas, Melissa Latter, Vincent Dore, Amir Fazlollahi, Pierrick Bourgeat, Victor L. Villemagne, Elizabeth J. Coulson, Stephen Rose
Summary: The dysfunction of the cholinergic basal forebrain neurotransmitter system has been found to play an important role in cognitive decline and dementia. A study used a validated method to directly measure cholinergic terminal integrity and investigated its value for assessing cholinergic denervation in the cortex and associated cognitive deficits. The results showed that there was a significant global reduction of cholinergic terminal integrity in the cortex of participants with mild cognitive impairment compared to cognitively unimpaired controls. The study also found correlations between the cholinergic terminal integrity and brain volumes, but no association with amyloid-beta status. The findings suggest the potential of using this method for early detection of cholinergic dysfunction in dementia.
NEUROIMAGE-CLINICAL
(2022)