From chronic stress and anxiety to neurodegeneration: Focus on neuromodulation of the axon initial segment
Апстракт
To adapt to the sustained demands of chronic stress, discrete brain circuits undergo structural and functional changes often resulting in anxiety disorders. In some individuals, anxiety disorders precede the development of motor symptoms of Parkinson's disease (PD) caused by degeneration of neurons in the substantia nigra (SN). Here, we present a circuit framework for probing a causal link between chronic stress, anxiety, and PD, which postulates a central role of abnormal neuromodulation of the SN's axon initial segment by brainstem inputs. It is grounded in findings demonstrating that the earliest PD pathologies occur in the stress-responsive, emotion regulation network of the brainstem, which provides the SN with dense aminergic and cholinergic innervation. SN's axon initial segment (AIS) has unique features that support the sustained and bidirectional propagation of activity in response to synaptic inputs. It is therefore, especially sensitive to circuit-mediated stress-induced imb...alance of neuromodulation, and thus a plausible initiating site of neurodegeneration. This could explain why, although secondary to pathophysiologies in other brainstem nuclei, SN degeneration is the most extensive. Consequently, the cardinal symptom of PD, severe motor deficits, arise from degeneration of the nigrostriatal pathway rather than other brainstem nuclei. Understanding when and how circuit dysfunctions underlying anxiety can progress to neurodegeneration, raises the prospect of timed interventions for reversing, or at least impeding, the early pathophysiologies that lead to PD and possibly other neurodegenerative disorders.
Кључне речи:
Anxiety / Axon initial segment / Neurodegeneration / Neuromodulation / Parkinson's diseaseИзвор:
Handbook of Clinical Neurology, 2022, 184, 481-495Напомена:
- Chapter 32
DOI: 10.1016/B978-0-12-819410-2.00025-4
PubMed: 35034756
Scopus: 2-s2.0-85122660154
Институција/група
VinčaTY - CHAP AU - Radulović, Jelena AU - Ivković, Sanja AU - Adžić, Miroslav PY - 2022 UR - https://vinar.vin.bg.ac.rs/handle/123456789/10136 AB - To adapt to the sustained demands of chronic stress, discrete brain circuits undergo structural and functional changes often resulting in anxiety disorders. In some individuals, anxiety disorders precede the development of motor symptoms of Parkinson's disease (PD) caused by degeneration of neurons in the substantia nigra (SN). Here, we present a circuit framework for probing a causal link between chronic stress, anxiety, and PD, which postulates a central role of abnormal neuromodulation of the SN's axon initial segment by brainstem inputs. It is grounded in findings demonstrating that the earliest PD pathologies occur in the stress-responsive, emotion regulation network of the brainstem, which provides the SN with dense aminergic and cholinergic innervation. SN's axon initial segment (AIS) has unique features that support the sustained and bidirectional propagation of activity in response to synaptic inputs. It is therefore, especially sensitive to circuit-mediated stress-induced imbalance of neuromodulation, and thus a plausible initiating site of neurodegeneration. This could explain why, although secondary to pathophysiologies in other brainstem nuclei, SN degeneration is the most extensive. Consequently, the cardinal symptom of PD, severe motor deficits, arise from degeneration of the nigrostriatal pathway rather than other brainstem nuclei. Understanding when and how circuit dysfunctions underlying anxiety can progress to neurodegeneration, raises the prospect of timed interventions for reversing, or at least impeding, the early pathophysiologies that lead to PD and possibly other neurodegenerative disorders. T2 - Handbook of Clinical Neurology T1 - From chronic stress and anxiety to neurodegeneration: Focus on neuromodulation of the axon initial segment VL - 184 SP - 481 EP - 495 DO - 10.1016/B978-0-12-819410-2.00025-4 ER -
@inbook{ author = "Radulović, Jelena and Ivković, Sanja and Adžić, Miroslav", year = "2022", abstract = "To adapt to the sustained demands of chronic stress, discrete brain circuits undergo structural and functional changes often resulting in anxiety disorders. In some individuals, anxiety disorders precede the development of motor symptoms of Parkinson's disease (PD) caused by degeneration of neurons in the substantia nigra (SN). Here, we present a circuit framework for probing a causal link between chronic stress, anxiety, and PD, which postulates a central role of abnormal neuromodulation of the SN's axon initial segment by brainstem inputs. It is grounded in findings demonstrating that the earliest PD pathologies occur in the stress-responsive, emotion regulation network of the brainstem, which provides the SN with dense aminergic and cholinergic innervation. SN's axon initial segment (AIS) has unique features that support the sustained and bidirectional propagation of activity in response to synaptic inputs. It is therefore, especially sensitive to circuit-mediated stress-induced imbalance of neuromodulation, and thus a plausible initiating site of neurodegeneration. This could explain why, although secondary to pathophysiologies in other brainstem nuclei, SN degeneration is the most extensive. Consequently, the cardinal symptom of PD, severe motor deficits, arise from degeneration of the nigrostriatal pathway rather than other brainstem nuclei. Understanding when and how circuit dysfunctions underlying anxiety can progress to neurodegeneration, raises the prospect of timed interventions for reversing, or at least impeding, the early pathophysiologies that lead to PD and possibly other neurodegenerative disorders.", journal = "Handbook of Clinical Neurology", booktitle = "From chronic stress and anxiety to neurodegeneration: Focus on neuromodulation of the axon initial segment", volume = "184", pages = "481-495", doi = "10.1016/B978-0-12-819410-2.00025-4" }
Radulović, J., Ivković, S.,& Adžić, M.. (2022). From chronic stress and anxiety to neurodegeneration: Focus on neuromodulation of the axon initial segment. in Handbook of Clinical Neurology, 184, 481-495. https://doi.org/10.1016/B978-0-12-819410-2.00025-4
Radulović J, Ivković S, Adžić M. From chronic stress and anxiety to neurodegeneration: Focus on neuromodulation of the axon initial segment. in Handbook of Clinical Neurology. 2022;184:481-495. doi:10.1016/B978-0-12-819410-2.00025-4 .
Radulović, Jelena, Ivković, Sanja, Adžić, Miroslav, "From chronic stress and anxiety to neurodegeneration: Focus on neuromodulation of the axon initial segment" in Handbook of Clinical Neurology, 184 (2022):481-495, https://doi.org/10.1016/B978-0-12-819410-2.00025-4 . .