The mechanisms of perineuronal net abnormalities in contributing aging and neurological diseases

Dong, Yixiao; Zhao, Kunkun; Qin, Xuemei; Du, Guanhua; Gao, Li

doi:10.1016/j.arr.2023.102092

Cited by 7 publications

(2 citation statements)

References 170 publications

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“…In human abducens nucleus, INTs could be discerned by their consistent and prominent PN ensheathment contrary to motoneurons, which varied in immunolabeling intensity ( Horn et al, 2018 ). An argument could be made that the age of the human donors in comparison to the relative age of the monkey could play a role in a hypothetical loss of PN integrity, as PN envelopment density could be altered by aging in people, as reported in several neurodegenerative conditions as well as other species ( Sugitani et al, 2021 ; Dong et al, 2023 ). So far, our unreported research contradicts this, as we have seen the existence of the motoneurons with weak PNs in tissues from donors with varying ages, or with neurodegenerative conditions such as ALS or anti-GAD syndrome associated opsoclonus.…”

Section: Discussionmentioning

confidence: 99%

Ion channel profiles of extraocular motoneurons and internuclear neurons in human abducens and trochlear nuclei

Mayadali,

Chertes,

Sinicina

et al. 2024

Front. Neuroanat.

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IntroductionExtraocular muscles are innervated by two anatomically and histochemically distinct motoneuron populations: motoneurons of multiply-innervated fibers (MIF), and of singly-innervated fibers (SIF). Recently, it has been established by our research group that these motoneuron types of monkey abducens and trochlear nuclei express distinct ion channel profiles: SIF motoneurons, as well as abducens internuclear neurons (INT), express strong Kv1.1 and Kv3.1b immunoreactivity, indicating their fast-firing capacity, whereas MIF motoneurons do not. Moreover, low voltage activated cation channels, such as Cav3.1 and HCN1 showed differences between MIF and SIF motoneurons, indicating distinct post-inhibitory rebound characteristics. However, the ion channel profiles of MIF and SIF motoneurons have not been established in human brainstem tissue.MethodsTherefore, we used immunohistochemical methods with antibodies against Kv, Cav3 and HCN channels to (1) examine the human trochlear nucleus in terms of anatomical organization of MIF and SIF motoneurons, (2) examine immunolabeling patterns of ion channel proteins in the distinct motoneurons populations in the trochlear and abducens nuclei.ResultsIn the examination of the trochlear nucleus, a third motoneuron subgroup was consistently encountered with weak perineuronal nets (PN). The neurons of this subgroup had -on average- larger diameters than MIF motoneurons, and smaller diameters than SIF motoneurons, and PN expression strength correlated with neuronal size. Immunolabeling of various ion channels revealed that, in general, human MIF and SIF motoneurons did not differ consistently, as opposed to the findings in monkey trochlear and abducens nuclei. Kv1.1, Kv3.1b and HCN channels were found on both MIF and SIF motoneurons and the immunolabeling density varied for multiple ion channels. On the other hand, significant differences between SIF motoneurons and INTs were found in terms of HCN1 immunoreactivity.DiscussionThese results indicated that motoneurons may be more variable in human in terms of histochemical and biophysiological characteristics, than previously thought. This study therefore establishes grounds for any histochemical examination of motor nuclei controlling extraocular muscles in eye movement related pathologies in the human brainstem.

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Section: Discussionmentioning

confidence: 99%

Ion channel profiles of extraocular motoneurons and internuclear neurons in human abducens and trochlear nuclei

Mayadali,

Chertes,

Sinicina

et al. 2024

Front. Neuroanat.

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“…Currently, we are witnessing unprecedented progress in research both on the hereditary and ontogenetic mechanisms underlying brain plasticity at various levels, from single synapses to large neuronal networks; perineuronal nets (PNN) can be viewed as an example of this kind [1]. These special structures of the extracellular matrix (ECM) ensheath synapses in large neuronal populations in many regions of the brain and spinal cord, thereby affecting synaptic and neuronal plasticity [2]. Mutations of the genes encoding the PNN components (NCAN, BCAN) are linked to hereditary risks of psychiatric and neurological disorders, so that a correlation of mutations to the severity of behavioral outcomes can be traced in human patients [3].…”

Section: Introductionmentioning

confidence: 99%

Perineuronal Net Microscopy: From Brain Pathology to Artificial Intelligence

Paveliev,

Egorchev,

Musin

et al. 2024

IJMS

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Perineuronal nets (PNN) are a special highly structured type of extracellular matrix encapsulating synapses on large populations of CNS neurons. PNN undergo structural changes in schizophrenia, epilepsy, Alzheimer’s disease, stroke, post-traumatic conditions, and some other brain disorders. The functional role of the PNN microstructure in brain pathologies has remained largely unstudied until recently. Here, we review recent research implicating PNN microstructural changes in schizophrenia and other disorders. We further concentrate on high-resolution studies of the PNN mesh units surrounding synaptic boutons to elucidate fine structural details behind the mutual functional regulation between the ECM and the synaptic terminal. We also review some updates regarding PNN as a potential pharmacological target. Artificial intelligence (AI)-based methods are now arriving as a new tool that may have the potential to grasp the brain’s complexity through a wide range of organization levels—from synaptic molecular events to large scale tissue rearrangements and the whole-brain connectome function. This scope matches exactly the complex role of PNN in brain physiology and pathology processes, and the first AI-assisted PNN microscopy studies have been reported. To that end, we report here on a machine learning-assisted tool for PNN mesh contour tracing.

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Aging-associated weakening of the action potential in fast-spiking interneurons in the human neocortex

Szegedi,

Tiszlavicz,

Furdan

et al. 2024

Journal of Biotechnology

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The mechanisms of perineuronal net abnormalities in contributing aging and neurological diseases

Cited by 7 publications

References 170 publications

Ion channel profiles of extraocular motoneurons and internuclear neurons in human abducens and trochlear nuclei

Ion channel profiles of extraocular motoneurons and internuclear neurons in human abducens and trochlear nuclei

Perineuronal Net Microscopy: From Brain Pathology to Artificial Intelligence

Aging-associated weakening of the action potential in fast-spiking interneurons in the human neocortex

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