Structural aspects of the aging invertebrate brain

Koch, Sandra C; Nelson, Annie; Hartenstein, Volker

doi:10.1007/s00441-020-03314-6

Cited by 8 publications

(9 citation statements)

References 173 publications

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“…Subsequent studies corroborated it by showing a decline in cortical neuron density, as well as cell loss in cortical and subcortical areas of elderly humans and non-human primates [47][48][49]. However, with the advancement of stereological methods new studies have identified these earlier data as confounding and likely biased by shrinkage artefacts and the mistaken inclusion of diseased samples [50,51]. Yet, presynaptic terminal count was negatively correlated with age in individuals older than 60 years, averaging thus a 20% decrease in density of presynaptic terminals within the frontal cortex [52].…”

Section: Aging-related Microstructural Synaptic Disconnectionmentioning

confidence: 91%

“…Some changes though may depend on whether the aged animal behaves cognitively normal or not [66]. Finally, even though the effects of aging are mostly drawn from the vertebrate's brain, typically mammals, notably aged invertebrates such as insects, including fruit flies, honeybees, crickets and cockroaches also manifest a range of disconnectionlike synaptic alterations [51].…”

Section: Aging-related Microstructural Synaptic Disconnectionmentioning

confidence: 99%

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The times they are a-changin’: a proposal on how brain flexibility goes beyond the obvious to include the concepts of “upward” and “downward” to neuroplasticity

Diniz

Crestani²

2022

Mol Psychiatry

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Since the brain was found to be somehow flexible, plastic, researchers worldwide have been trying to comprehend its fundamentals to better understand the brain itself, make predictions, disentangle the neurobiology of brain diseases, and finally propose up-to-date treatments. Neuroplasticity is simple as a concept, but extremely complex when it comes to its mechanisms. This review aims to bring to light an aspect about neuroplasticity that is often not given enough attention as it should, the fact that the brain’s ability to change would include its ability to disconnect synapses. So, neuronal shrinkage, decrease in spine density or dendritic complexity should be included within the concept of neuroplasticity as part of its mechanisms, not as an impairment of it. To that end, we extensively describe a variety of studies involving topics such as neurodevelopment, aging, stress, memory and homeostatic plasticity to highlight how the weakening and disconnection of synapses organically permeate the brain in so many ways as a good practice of its intrinsic physiology. Therefore, we propose to break down neuroplasticity into two sub-concepts, “upward neuroplasticity” for changes related to synaptic construction and “downward neuroplasticity” for changes related to synaptic deconstruction. With these sub-concepts, neuroplasticity could be better understood from a bigger landscape as a vector in which both directions could be taken for the brain to flexibly adapt to certain demands. Such a paradigm shift would allow a better understanding of the concept of neuroplasticity to avoid any data interpretation bias, once it makes clear that there is no morality with regard to the organic and physiological changes that involve dynamic biological systems as seen in the brain.

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Section: Aging-related Microstructural Synaptic Disconnectionmentioning

confidence: 91%

Section: Aging-related Microstructural Synaptic Disconnectionmentioning

confidence: 99%

The times they are a-changin’: a proposal on how brain flexibility goes beyond the obvious to include the concepts of “upward” and “downward” to neuroplasticity

Diniz

Crestani²

2022

Mol Psychiatry

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“…The geometrical structure of its dendritic arbor determines the receiving region of input, synaptic density, numerous presynaptic partners, and certain physiological properties (Lefebvre et al 2015) . Rather than neuronal loss, alterations in the dendrite arbors, axonal collaterals, and synaptic density are anatomically detectable in the aged brains (Koch et al 2021) . In the previous study, we identified the m 6 A reader YTHDF2 as a negative regulator for dendrite development and maintenance of retinal ganglion cells (RGCs) (Niu et al 2022) , which inspired us to further explore whether YTHDF2 regulates RGC dendrite morphonology in the aged mice.…”

Section: Resultsmentioning

confidence: 99%

Ythdf2ablation protects aged retina from RGC dendrite shrinking and visual decline

Niu

Long

Zhang

et al. 2023

Preprint

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Aging-related retinal degeneration and vision loss have been severely affecting the elder worldwide. Previously we showed that the m6A reader YTHDF2 is a negative regulator for dendrite development and maintenance of retinal ganglion cells (RGC) in mice(Niu et al. 2022). Here, we show that conditional ablation ofYthdf2protects retina from RGC dendrite shrinking and vision loss in the aged mice. Further, we identifyHspa12aandIslr2as the YTHDF2 target mRNAs mediating these effects. Together our results indicate that m6A modification regulates retinal degeneration caused by aging, which might provide therapeutical potentials for developing new treatment approaches against aging-related vision loss.

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“…In the case of the VA1lm ORNs, this decrease appears to be a pruning stage that is followed by maintenance of a steady state number of synapses. For DA1 ORNs, however, this occurs later in adulthood, perhaps as a period of senescence (Koch et al, 2021). It is tempting to speculate that these temporal patterns of synapse addition and removal may be related to each the specific function of each class of ORNs.…”

Section: Discussionmentioning

confidence: 99%

Different olfactory neuron classes use distinct temporal and molecular programs to complete synaptic development

Aimino

DePew

Restrepo

et al. 2022

Preprint

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Developing neurons must meet core molecular, cellular, and temporal requirements to ensure the correct formation of synapses, resulting in functional circuits. However, because of the vast diversity in neuronal class and function, it is unclear whether or not all neurons use the same organizational mechanisms to form synaptic connections and achieve functional and morphological maturation. Moreover, it remains unknown if neurons united in a common goal and comprising the same sensory circuit develop on similar timescales and using identical molecular approaches to ensure the formation of the correct number of synapses. To begin to answer these questions, we took advantage of the Drosophila antennal lobe, a model olfactory circuit with remarkable genetic access and synapse-level resolution. Using tissue-specific genetic labeling of active zones, we performed a quantitative analysis of synapse formation in multiple classes of neurons throughout development and adulthood. We found that olfactory receptor neurons (ORNs), projection neurons (PNs), and local interneurons (LNs) each have unique time-courses of synaptic development, addition, and refinement, demonstrating that each class follows a distinct developmental program. This raised the possibility that these classes may also have distinct molecular requirements for synapse formation. We genetically altered neuronal activity in each neuronal subtype and observed differing effects on synapse number based on the neuronal class examined. Silencing neuronal activity in ORNs, PNs, and LNs impaired synaptic development but only in ORNs did enhancing neuronal activity influence synapse formation. ORNs and LNs demonstrated similar impairment of synaptic development with enhanced activity of a master kinase, GSK-3β, suggesting that neuronal activity and GSK-3β kinase activity function in a common pathway. ORNs also, however, demonstrated impaired synaptic development with GSK-3β loss-of-function, suggesting additional activity-independent roles in development. Ultimately, our results suggest that the requirements for synaptic development are not uniform across all neuronal classes with considerable diversity existing in both their developmental timeframes and molecular requirements. These findings provide novel insights into the mechanisms of synaptic development and lay the foundation for future work determining their underlying etiologies.

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Structural aspects of the aging invertebrate brain

Cited by 8 publications

References 173 publications

The times they are a-changin’: a proposal on how brain flexibility goes beyond the obvious to include the concepts of “upward” and “downward” to neuroplasticity

The times they are a-changin’: a proposal on how brain flexibility goes beyond the obvious to include the concepts of “upward” and “downward” to neuroplasticity

Ythdf2ablation protects aged retina from RGC dendrite shrinking and visual decline

Different olfactory neuron classes use distinct temporal and molecular programs to complete synaptic development

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